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The antiapoptotic effects of conditioned medium from bone marrow-derived mesenchymal stromal stem cells on cyclophosphamide-induced testicular damage in rat: An experimental study اثرات ضد آپوپتوزی محیط مشروط مشتق از سلول بنیادی مزانشیمی مغز استخوان بر آسیب بافت بیضه در رت های دریافت کننده سیکلوفسفامید: یک مطالعه آزمایشگاهی 2 1 مقدمه: سیکلوفسفامید (CP) اثرات منفی بر سیستم تولید­مثل دارد. سلول­های بنیادی و متابولیت­های آنها جهت افزایش باروری پس از شیمی درمانی مورد استفاده قرار گرفته­اند. هدف: این مطالعه با هدف بررسی تأثیر محیط مشروط (Conditioned medium: CM) مشتق شده از سلول­های بنیادی مزانشیمی مشتق از مغز استخوان بر اثرات سمی CP بر بیضه­ها انجام شد. مواد و روش­ ها: سلول‌های بنیادی مزانشیمی مغز استخوان استخراج، محیط مشروط جمع‌آوری و 25 برابر تغلیظ شد. 24 سر موش­های صحرایی نر نژاد ویستار (8 هفته، 250-200 گرم) به صورت تصادفی به 4 گروه تقسیم شدند: کنترل، CP، CP+DMEM، CP+CM .CP به میزان 100 میلی­گرم بر کیلوگرم به شکل تک دوز تزریق شد. دو هفته پس از تجویز سیکلوفسفامید، CM از طریق مجرای وابران بیضه تزریق شد. پارامترهای اسپرم، هیستوپاتولوژی بیضه و سطح تستوسترون دو ماه پس از درمان بررسی شد. بیان ژن‌های Bax و Bcl2 توسط real-time polymerase chain reaction مورد ارزیابی قرار گرفت. نتایج: CP بر بافت‌شناسی بیضه (001/0 < p) و کیفیت اسپرم (001/0 < p) تأثیر منفی داشت. CP بیان ژن­های مرتبط با آپوپتوز را تغییر داد (001/0 < p). درمان با CM بیان Bax را صورت معنی­داری کاهش داد (001/0 < p)، در حالی که بیان Bcl2 را به طور معنی­داری افزایش نشان داد (01/0 = p). CP تعداد اسپرم (03/0 = p)، زنده­مانی (001/0 < p) تحرک (001/0 < p)، تعداد اسپرماتوگونی (001/0 < p) و ضخامت اپیتلیال لوله‌های بیضه (02/0 = p) را بهبود داد. نتیجه­ گیری: این یافته‌ها نشان می‌دهد که CM تولید شده از سلول­های بنیادی مزانشیمی مشتق از مغز استخوان ممکن است در درمان­های ناباروری ارزشمند باشد و عوارض جانبی CP را کاهش دهد. کلمات کلیدی: سلول­های بنیادی مزانشیمی مغز استخوان، سیکلوفسفامید، محیط شرطی شده، آپوپتوز، اسپرماتوژنز 2 Abstract Background: Cyclophosphamide (CP) has some negative effects on the reproductive system. Stem cells and their metabolites are being utilized to enhance fertility after chemotherapy. Objective: This study aimed to investigate the impact of conditioned medium (CM) derived from bone marrow mesenchymal stromal stem cells (BM-MSCs) on the toxic effects of CP on testicles. Materials and Methods: BM-MSCs were isolated, a CM was collected and 25-fold concentrated. 24 male Wistar rats (8 wk, 200-250 gr) were randomly divided into following groups: control, CP, CP+Dulbecco’s Modified Eagle Medium (DMEM), CP+CM. CP was given at a single dose of 100 mg/kg. 2 wk after the CP administration, CM was injected into the testicular efferent duct. Sperm parameters, testicular histopathology, and the level of testosterone were analyzed 2 months after treatment. The expression of B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) genes were evaluated by real-time polymerase chain reaction. Results: CP had a negative effect on testis histology (p < 0.001) and sperm quality (p < 0.001). It changed the expression of genes associated with apoptosis (p < 0.001). Treatment with CM reduced the expression of Bax (p < 0.001), while significantly increasing the expression of Bcl2 (p = 0.01). It improved sperm count (p = 0.03), viability (p < 0.001), motility (p < 0.001), spermatogonial count (p < 0.001), and epithelial thickness of testicular tubules (p = 0.02). Conclusion: These findings suggest that CM produced from BM-MSCs may be valuable for therapeutic approaches in reproductive medicine and may lessen the side effects of CP. 89 100 2023/10/1 1402/7/9 2024/02/7 1402/11/18 Zeynab Esmailpour Zeynab Esmailpour Students Research Committee, Arak University of Medical Sciences, Arak, Iran. ایران zeynabes265@gmail.com Soheila Madadi Soheila Madadi Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. ایران soheila.madadi@yahoo.com Maryam Baazm Maryam Baazm Department of Anatomy, School of Medicine, Arak University of Medical Sciences, Arak, Iran. Molecular and Medicine Research Center, School of Medicine, Arak University of Medical Sciences, Arak, Iran. ایران dr.baazm@arakmu.ac.ir Bone marrow mesenchymal stem cells Cyclophosphamide Conditioned medium Apoptosis Spermatogenesis. سلول­های بنیادی مزانشیمی مغز استخوان سیکلوفسفامید محیط شرطی شده آپوپتوز اسپرماتوژنز 1. El Gharabawy GS, Abd Allah EE-DE, Amr IM, Elmitwalli M. Histological and immunohistochemical study of the effect of cyclophosphamide on testis of male adult albino rats and the possible protective role of vitamin E. Egypt J Hospital Med 2019; 77: 5930-5946.##2. Fusco R, Salinaro AT, Siracusa R, D’Amico R, Impellizzeri D, Scuto M, et al. Hidrox® counteracts cyclophosphamide-induced male infertility through NRF2 pathways in a mouse model. Antioxidants 2021; 10: 778.##3. Abram McBride J, Lipshultz LI. Male fertility preservation. Curr Urol Rep 2018; 19: 49.##4. Yuan Q-L, Zhang Y-G, Chen Q. Mesenchymal stem cell (MSC)‐derived extracellular vesicles: Potential therapeutics as MSC trophic mediators in regenerative medicine. Anat Rec 2020; 303: 1735-1742.##5. Sagaradze G, Grigorieva O, Nimiritsky P, Basalova N, Kalinina N, Akopyan Z, et al. Conditioned medium from human mesenchymal stromal cells: Towards the clinical translation. Int J Mol Sci 2019; 20: 1656.##6. Benavides-Castellanos MP, Garzón-Orjuela N, Linero I. Effectiveness of mesenchymal stem cell-conditioned medium in bone regeneration in animal and human models: A systematic review and meta-analysis. Cell Regen 2020; 9: 5.##7. Veronesi F, Borsari V, Sartori M, Orciani M, Mattioli‐Belmonte M, Fini M. The use of cell conditioned medium for musculoskeletal tissue regeneration. J Cell Physiol 2018; 233: 4423-4442.##8. Ogata K, Katagiri W, Osugi M, Kawai T, Sugimura Y, Hibi H, et al. Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model. Bone 2015; 74: 95-105.##9. Cai Y-T, Xiong C-L, Shen S-L, Rao J-P, Liu T-S, Qiu F. Mesenchymal stem cell‐secreted factors delayed spermatogenesis injuries induced by busulfan involving intercellular adhesion molecule regulation. Andrologia 2019; 51: e13285.##10. Abdollahifar M-A, Azad N, Faraji Sani M, Raoofi A, Abdi S, Aliaghaei A, et al. Impaired spermatogenesis caused by busulfan is partially ameliorated by treatment with conditioned medium of adipose tissue derived mesenchymal stem cells. Biotech Histochem 2022; 97: 107-117.##11. Mahiddine FY, Kim JW, Qamar AY, Ra JC, Kim SH, Jung EJ, et al. Conditioned medium from canine amniotic membrane-derived mesenchymal stem cells improved dog sperm post-thaw quality-related parameters. Animals 2020; 10: 1899.##12. Shah SM, Saini N, Singh MK, Manik R, Singla SK, Palta P, et al. Testicular cell-conditioned medium supports embryonic stem cell differentiation toward germ lineage and to spermatocyte-and oocyte-like cells. Theriogenology 2016; 86: 715-729.##13. Akyash F, Aflatoonian R, Farashahi Yazd E, Golzadeh J, Tahajjodi S, Moore H, et al. Testicular sperm extraction derived cells conditioned medium as an in vitro niche supports germ cells development from human embryonic stem cells. 35th Annual Meeting of the European Society for Human Reproduction and Embryology; 24-26 June 2019; Vienna, Austria. 2019; 34: i333.##14. Khanmohammadi N, Sameni HR, Mohammadi M, Pakdel A, Mirmohammadkhani M, Parsaie H, et al. Effect of transplantation of bone marrow stromal cell-conditioned medium on ovarian function, morphology and cell death in cyclophosphamide-treated rats. Cell J 2018; 20: 10-18.##15. Nihashi Y, Yamamoto M, Shimosato T, Takaya T. Myogenetic oligodeoxynucleotide restores differentiation and reverses inflammation of myoblasts aggravated by cancer-conditioned medium. Muscles 2022; 1: 111-120.##16. Rezaei Sh, Hosseinimehr SJ, Zargari M, Karimpour Malekshah A, Mirzaei M, Talebpour Amiri F. Protective effects of sinapic acid against cyclophosphamide‐induced testicular toxicity via inhibiting oxidative stress, caspase‐3 and NF‐kB activity in BALB/c mice. Andrologia 2021; 53: e14196.##17. Aghaie S, Nikzad H, Amini Mahabadi J, Taghizadeh M, Azami-Tameh A, Taherian A, et al. Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide. Anat Sci Int 2016; 91: 382-390.##18. Gul M, Hildorf S, Dong L, Thorup J, Hoffmann ER, Jensen CFS, et al. Review of injection techniques for spermatogonial stem cell transplantation. Hum Reprod Update 2020; 26: 368-391.##19. Mizoguchi T. [Characterization of bone marrow mesenchymal stem cells]. Clin Calcium 2017; 27: 779-787. (in Japanese)##20. Zohour Soleimani M, Jalali Mashayekhi F, Mousavi Hasanzade M, Baazm M. Alteration in CatSper1 and 2 genes expression, sperm parameters and testis histology in varicocelized rats. Int J Reprod BioMed 2018; 16: 183-190.##21. Jalili C, Kamani M, Roshankhah S, Sadeghi H, Salahshoor MR. Effect of Falcaria vulgaris extracts on sperm parameters in diabetic rats. Andrologia 2018; 50: e13130.##22. Hemati U, Moshajari M, Jalali Mashayekhi F, Bayat M, Moslemi A, Baazm M. The effect of curcumin on NRF2/Keap1 signalling pathway in the epididymis of mouse experimental cryptorchidism. Andrologia 2022; 54: e14532.##23. Babaei A, Kheradmand N, Baazm M, Nejati N, Khalatbari M. Protective effect of vitamin E on sperm parameters in rats infected with Candida albicans. Andrologia 2020; 52: e13593.##24. Gassei K, Orwig KE. Experimental methods to preserve male fertility and treat male factor infertility. Fertil Steril 2016; 105: 256-266.##25. Picton HM, Wyns Ch, Anderson RA, Goossens E, Jahnukainen K, Kliesch S, et al. A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys. Hum Reprod 2015; 30: 2463-2475.##26. Anan HH, Wahba NS, Abdallah MA, Mohamed DA. Histological and immunohistochemical study of cyclophosphamide effect on adult rat testis. Int J Sci Rep 2017; 3: 39-48.##27. Afkhami‐Ardakani M, Hasanzadeh Sh, Shahrooz R, Delirezh N, Malekinejad H. Spirulina platensis (Arthrospira platensis) attenuates cyclophosphamide‐induced reproductive toxicity in male Wistar rats: Evidence for sperm apoptosis and p53/Bcl‐2 expression. J Food Biochem 2021; 45: e13854.##28. Alkhalaf MI, Alansari WS, Alshubaily FA, Alnajeebi AM, Eskandrani AA, Tashkandi MA, et al. Chemoprotective effects of inositol hexaphosphate against cyclophosphamide-induced testicular damage in rats. Sci Rep 2020; 10: 12599.##29. Shittu SA, Shittu Sh-T, Akindele OO, Kunle-Alabi OT, Raji Y. Protective action of N-acetylcysteine on sperm quality in cyclophosphamide-induced testicular toxicity in male Wistar rats. JBRA Assist Reprod 2019; 23: 83-90.##30. Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol 2017; 13: 525-536.##31. Al-Dhalemi DM, Al-Hedaby FM. Evaluation of protective effect of cardamomum extraction against cyclophosphamide induced testicular degeneration. Biochem Cell Arch 2021; 21: 4231.##32. Sadeghzadeh F, Sadeghzadeh A, Changizi-Ashtiyani S, Bakhshi S, Mashayekhi FJ, Mashayekhi M, et al. The effect of hydro-alcoholic extract of Ceratonia Silique L. on spermatogenesis index in rats treated with cyclophosphamide: An experimental study. Int J Reprod BioMed 2020; 18: 295-306.##33. Cetinkaya-Un B, Un B, Akpolat M, Andic F, Yazir Y. Human amnion membrane-derived mesenchymal stem cells and conditioned medium can ameliorate X-irradiation-induced testicular injury by reducing endoplasmic reticulum stress and apoptosis. Reprod Sci 2022; 29: 944-954.##34. Liang X, Lin F, Ding Y, Zhang Y, Li M, Zhou X, et al. Conditioned medium from induced pluripotent stem cell-derived mesenchymal stem cells accelerates cutaneous wound healing through enhanced angiogenesis. Stem Cell Res Ther 2021; 12: 295.##35. Sharifian P, Yari S, Hasanein P, Manteghi Nezhad Y. Conditioned medium of bone marrow mesenchymal stem cells improves sperm parameters and reduces histological alteration in rat testicular ischaemia/reperfusion model. Andrologia 2022; 54: e14624.##36. Saleem R, Mohamed-Ahmed S, Elnour R, Berggreen E, Mustafa K, Al-Sharabi N. 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Mode of delivery alters sensitivity to thermal and chemical stimuli in adult rats: An experimental study روش زایمان حساسیت به محرک های گرمایی و شیمیایی را در زاده های ماده بالغ در موش های صحرایی تغییر می دهد: یک مطالعه تجربی 2 1 مقدمه: نشان داده شده است که روش زایمان تغییرات دراز مدت و پایدار در فیزیولوژی زاده­ها ایجاد می­کند. هدف: ارزیابی ارتباط بین روش زایمان و حساسیت به محرک­های حرارتی و شیمیایی در زاده­های ماده بالغ در موش­های صحرایی. مواد و روش ­ها: در این مطالعه 56 موش صحرایی ماده بالغ (220-200 گرم) متولد شده با زایمان واژینال (28 = n) یا سزارین (28 = n) استفاده شد. التهاب پا القا شده با فرمالین استفاده شد. آستانه درد حرارتی در تست­های کشش دم و صفحه داغ تعیین شدند. همچنین، سطوح نخاعی پروتئین­های c-fos و c-jun در تست وسترن بلات ارزیابی شدند. نتایج: درد القا شده با فرمالین در موش­های صحرایی متولد شده با سزارین در مقایسه با موش­های متولد شده با زایمان طبیعی کاهش یافت (001/0 < p). آستانه پایه درد و بی­دردی القا شده با مورفین در گروه سزارینی در مقایسه با گروه متولد شده با زایمان طبیعی افزایش یافت. آزمایش ایمنوبلات یک کاهش قابل توجه در سطوح پروتئین c-fos و c-jun در حیوانات سزارینی در مقایسه با گروه زایمان طبیعی نشان داد (01/0 < p). درمان با مورفین مقادیر پروتئین­ها را در گروه سزارین افزایش داد (05/0 < p). نتیجه­ گیری: در مجموع موش­های متولد شده با سزارین در مقایسه با موش­های حاصل از زایمان طبیعی حساسیت کمتری به درد نخاعی و فعالیت عصبی نشان دادند.    2 Background: The mode of delivery might prompt a long-lasting alteration in physiological and behavioral responsiveness in offspring. Objective: This study was intended to evaluate if the mode of delivery could alter sensitivity to thermal and chemical stimuli in female rats. Materials and Methods: 56 adult female Wistar rats (200-220 gr) that were born by vaginal or cesarean section (C-section) were used (n = 28/each). Inflammatory pain was induced by subcutaneous injection of formalin into the hind paw. The thermal nociceptive threshold was determined by tail-flick and hot plate tests. Besides, the Western blot test was used to evaluate the spinal cord levels of c-Fos and c-Jun proteins. Results: Formalin-induced inflammation was significantly decreased in C-section group as compared to vaginally born rats (p < 0.001). The baseline nociceptive threshed and morphine-induced analgesia were significantly increased in C-section groups in comparison to vaginally born rats. In addition, the levels of c-Fos and c-Jun proteins were significantly decreased in the spinal cord of C-section rats as compared to vaginally born animals (p < 0.01). Morphine treatment could decrease the expression of c-Fos and c-Jun in the C-section group (p < 0.05). Conclusion: Overall, C-section rats showed lower spinal nociceptive processing and neuronal activity later in life, compared to the vaginal born rats. 101 110 2023/10/12023/04/6 1402/1/17 2024/02/72024/01/17 1402/10/27 Parastoo Nikkhouy Parastoo Nikkhouy Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran. ایران parastoo.nikkhouy@gmail.com Mehdi Abbasnejad Mehdi Abbasnejad Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran. ایران mabbas@uk.ac.ir Saeed Esmaeili-Mahani Saeed Esmaeili-Mahani Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran. Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. ایران semahani@uk.ac.ir Razieh Kooshki Razieh Kooshki Department of Biology, Faculty of Sciences, Lorestan University, Khorramabad, Iran. ایران kooshki.r@lu.ac.ir Childbirth C-section Nociception Inflammation Rats. زایمان سزارین درد التهاب موش های صحرایی 1. Negrini R, da Silva Ferreira RD, Guimarães DZ. Value-based care in obstetrics: Comparison between vaginal birth and caesarean section. BMC Pregnancy Childbirth 2021; 21: 333.##2. Chen H, Tan D. Cesarean section or natural childbirth? Cesarean birth may damage your health. Front Psychol 2019; 10: 351. ##3. Barba-Müller E, Craddock S, Carmona S, Hoekzema E. Brain plasticity in pregnancy and the postpartum period: Links to maternal caregiving and mental health. Arch Womens Ment Health 2019; 22: 289-299. ##4. Vasung L, Turk EA, Ferradal SL, Sutin J, Stout JN, Ahtam B, et al. 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Urtica pilulifera L. seed extract promotes folliculogenesis and alleviates the diminished ovarian reserve in the Balb/c mice model: An experimental study افزایش فولیکولوژنز و بهبود علایم در مدل ذخیره تخمدانی کاهش یافته در موش Balb/c توسط عصاره دانه گیاه انجره: یک مطالعه تجربی 2 1 مقدمه: بر اساس منابع طب سنتی ایرانی، دانه انجره یا (UPS) Urtica pilulifera L. اثرات مثبتی بر ناباروری زنان دارد. هدف: این مطالعه با هدف بررسی اثرات سودمند و مکانیسم زمینه­ای عصاره هیدروالکلی دانه انجره بر روی مدل ذخیره تخمدان کاهش یافته (DOR) القا شده توسط سیکلوفسفامید (CTX) در موش Balb/c انجام شد. مواد و روش­ ها: در این مطالعه حیوانی، یک تک دوز داخل صفاقی سیکلوفسفامید ( 75 میلی‌گرم بر کیلوگرم) برای ایجاد مدل DOR تجویز شد. 25 موش ماده Balb/c به طور تصادفی به 5 گروه شامل کنترل سالم (سالین نرمال)، مدل (DOR)، DOR+50, DOR+100, DOR+200 (mg/kg UPS) تقسیم شدند و به­مدت 14 روز گاواژ انجام شد. سطح هورمون­های استروئیدی، نشانگرهای استرس اکسیداتیو، آپوپتوز و تغییرات هیستوپاتولوژیک مورد بررسی قرار گرفت. شناسایی ترکیبات موجود در دانه گزنه با روش GC/Mass انجام شد. نتایج: نتایج نشان داد که عصاره انجره  (UPS)باعث کاهش غلظت مالون­دی­آلدهید (MDA) و آپوپتوز و همچنین افزایش فعالیت آنزیم سوپراکساید دیسموتاز (SOD) در مدل DOR به صورت وابسته به دوز می­شود. علاوه بر این، اثر تعدیل­کننده بر روی هورمون­های استروئیدی مانند FSH، LH و E2 اعمال می­کند. تجزیه و تحلیل هیستوپاتولوژیک پتانسیل درمانی عصاره UPS را نشان داد. ترکیبات شیمیایی اصلی UPS عبارت بودند از لینولئیک اسید (25/%59)، هگزادکانوییک اسید (36/%10) و اولئیک اسید (29/%8). نتیجه ­گیری: نتایج نشان داد که عصاره UPS دارای پتانسیل درمانی در مدل ذخیره تخمدانی کاهش­یافته یا DOR است و یک گزینه درمانی جایگزین ارائه می‌کند. این پتانسیل به کاهش استرس اکسیداتیو، تعدیل آپوپتوز و تنظیم هورمون­های استروئیدی نسبت داده می­شود که می­تواند با اثرات مفید مشاهده شده از اسیدهای چرب بر بهبود باروری مرتبط باشد. 2 Background: Urtica pilulifera L. seed (UPS) is a Persian traditional medicine prescription that positively affects female infertility. Objective: This study aimed to evaluate the beneficial effects of UPS on a diminished ovarian reserve (DOR) model induced by cyclophosphamide in Balb/c mice. Materials and Methods: A single intraperitoneal (75 mg/kg) of cyclophosphamide was administered to establish a DOR model. 25 female Balb/c mice (6-8 wk, 25 ± 2 gr) were randomly divided into 5 groups (n = 5/each), including control (normal saline), model (DOR), DOR+50, DOR+100, and DOR+200 (mg/kg UPS, gavage) groups for 14 days. The levels of follicle-stimulating hormone, luteinizing hormone, estradiol, malondialdehyde, superoxide dismutases, apoptosis, and histopathological alterations were analyzed. Gas chromatography-mass spectrometry analysis performed to identify the phytochemicals of the UPS. Results: It was observed that the UPS extract reduced malondialdehyde concentration and apoptosis in the DOR model as well as enhanced superoxide dismutases activity in the ovaries in a dose-dependent manner. Moreover, it exerted a modulatory effect on steroidal hormones such as follicle-stimulating hormone, luteinizing hormone, and estradiol. The histopathological analysis revealed the therapeutic potential of the UPS extract. The main chemical components of UPS were linoleic acid (59.25%), n-hexadecanoic acid (10.36%), and oleic acid (8.29%). Conclusion: The results indicated that the UPS extract has therapeutic potential in the DOR model. This potential is attributed to the reduction of oxidative stress, modulation of apoptosis, and regulation of steroidal hormones that may be associated with the observed beneficial effects of fatty acids on fertility improvement 111 126 2023/10/12023/04/62023/09/25 1402/7/3 2024/02/72024/01/172024/03/5 1402/12/15 Sharareh Hekmat Sharareh Hekmat Department of Traditional Pharmacy, School of Traditional Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran. ایران hekmat7193@yahoo.com Mohammad Sharifzadeh Mohammad Sharifzadeh Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. ایران msharifzadeh@tums.ac.ir Tayebeh Toliyat Tayebeh Toliyat Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. ایران toliyat@tums.ac.ir Roghayeh Savary Kouzehkonan Roghayeh Savary Kouzehkonan Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. ایران rsavary72@gmail.com Mozhgan Mehri Ardestani Mozhgan Mehri Ardestani Department of Persian Medicine, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran. ایران mozhgan_mehri@yahoo.com Malihe Tabarrai Malihe Tabarrai Department of Persian Medicine, School of Traditional Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran. ایران dr.mtabarrai@yahoo.com Seyede Nargess Sadati Lamardi Seyede Nargess Sadati Lamardi Department of Traditional Pharmacy, School of Traditional Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran. ایران n_sadati@tums.ac.ir Apoptosis Fatty acids Female infertility Herbal medicine Persian medicine Oxidative stress. آپوپتوز اسیدهای چرب ناباروری زنان داروهای گیاهی طب ایرانی استرس اکسیداتیو. 1. 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Folate gene polymorphisms CBS 844ins68 and RFC1 A80G and risk of Down syndrome offspring in young Iranian women: A cross-sectional study بررسی پلی مورفیسم های CBS 844ins68 و RFC1 A80G و ریسک بروز سندروم داون در مادران جوان ایرانی: یک مطالعه مقطعی 2 1 مقدمه: مطالعات سیتوژنتیک و همراهی نشان داده است که پلی‌مورفیسم‌های ژن­های فولات می‌تواند خطر عدم تفرق صحیح کروموزومی و آنوپلوئیدی را افزایش دهد. پلی‌مورفیسم‌های ژن متابولیسم‌کننده فولات در مادران مبتلا به سندرم داون (DSM) در جمعیت‌های مختلف مورد بررسی قرار گرفته است. حامل فولات کاهش یافته 1 (RFC-1) و سیستاتیونین بتا سنتاز (CBS) دو آنزیم کلیدی در متابولیسم فولات هستند. هدف: دو پلی­مورفیسم رایج CBS 844ins68 و RFC-1 A80G برای تعیین خطر احتمالی آنها در داشتن نوزادان DS در مادران جوان استان خوزستان، ایران مورد تجزیه و تحلیل قرار گرفتند. مواد و روش ­ها: این مطالعه بر روی 100 مادر دارای فرزند سندروم داون تریزومی 21 انجام شد. 100 مادر دارای همخوانی سن و قومیت با حداقل دو فرزند سالم و بدون سابقه بارداری غیرطبیعی به عنوان شاهد در نظر گرفته شدند. همه مادران از استان خوزستان بودند. شرکت­کنندگان از ژوئن 2019 تا آوریل 2021 جمع­آوری شدند. DNA ژنومی از خون محیطی استخراج شد. CBS-844ins68 و RFC-1-A80G به ترتیب با استفاده از PCR-electrophoresis و RFLP ژنوتیپ شدند. نتایج: در ارتباط با RFC-1، فراوانی ژنوتیپ­های AG و GG در مادران مبتلا به سندرم داون به طور معنی­داری بیشتر از مادران شاهد بود (ریسک خطر به ترتیب 38/2 و 07/3). ژنوتیپ هتروزیگوت CBS 844ins68 در بین مادران مبتلا به سندرم داون به طور معنی­داری بیشتر از شاهد بود (ریسک خطر 419/2). در نتیجه همزمانی وقوع هموزیگوت هر دو واریانت، ریسک خطر به طور قابل توجهی به 667/6 افزایش یافت. نتیجه ­گیری: پلی­مورفیسم­های مورد مطالعه احتمالاً استعداد داشتن فرزند سندروم داون را افزایش می­دهند. با این حال، قومیت، تغذیه و اپیستازی عوامل قابل توجهی هستند که باید در مطالعات آینده مورد ارزیابی قرار گیرند. کلمات کلیدی: سندروم داون، فولیک اسید، پلی­مورفیسم، CBS، RFC-1. 2 Background: Cytogenetics and association studies showed that folate gene polymorphisms can increase the risk of chromosomal nondisjunction and aneuploidies. The folate-metabolizing gene polymorphisms in Down syndrome mothers (DSM) have been assessed in a variety of populations. Reduced folate carrier 1 (RFC1) and cystathionine beta-synthase (CBS) are key enzymes in folate metabolism. Objective: 2 common polymorphisms, CBS 844ins68 and RFC1 A80G, were analyzed to determine their probable risk for having Down syndrome (DS) babies in young mothers of Khuzestan province, Iran. Materials and Methods: This study was conducted on 100 mothers who had trisomy 21 DS children. 100 age- and ethnic-matched mothers with at least 2 healthy children and no history of abnormal pregnancies were considered as control. The samples were collected from all the mothers from June 2019 to April 2021. Genomic DNA was extracted from peripheral blood. The CBS-844ins68 and RFC1-A80G were genotyped using polymerase chain reaction-electrophoresis and restriction fragment length polymorphism, respectively. Results: The frequency of RFC1 AG and GG genotypes in DSM was significantly higher than the control mothers (odds ratio [OR] of 2.38 and 3.07, respectively). The heterozygote genotype of CBS 844ins68 was significantly more prevalent among DSM than the control (OR: 2.419). The OR was significantly increased to 6.667 when the homozygote of both variants was found together. Conclusion: Studying polymorphisms possibly increases the susceptibility of having a DS child. However, ethnicity, nutrition, and epistatic interactions are considerable factors to be evaluated in future studies.   127 136 2023/10/12023/04/62023/09/252023/02/20 1401/12/1 2024/02/72024/01/172024/03/52024/02/3 1402/11/14 Neda Farajnezhad Neda Farajnezhad Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ایران farajnezhadn@gmail.com Pegah Ghandil Pegah Ghandil Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ایران pghandil@yahoo.com Maryam Tahmasebi-Birgani Maryam Tahmasebi-Birgani Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ایران tahmasebi.birgani62@gmail.com Javad Mohammadi-Asl Javad Mohammadi-Asl Noorgene Genetics Laboratory, Ahvaz, Iran. ایران mohammadiasl@gmail.com Down syndrome Folic acid Polymorphism CBS RFC1. سندروم داون فولیک اسید پلی­مورفیسم CBS RFC-1. 1. Moyer AJ, Gardiner K, Reeves RH. All creatures great and small: New approaches for understanding down syndrome genetics. Trends Genet 2021; 37: 444-459.##2. Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, Bianchi DW, et al. Down syndrome. Nat Rev Dis Primers 2020; 6: 9.##3. James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, Gibson JB, et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr 1999; 70: 495-501.##4. Ginani CTA, da Luz JRD, de Medeiros KS, Sarmento ACA, Coppedè F, das Graças Almeida M. Association of C677T and A1298C polymorphisms of the MTHFR gene with maternal risk for Down syndrome: A meta-analysis of case-control studies. Mutat Res Rev Mutat Res 2023; 792: 108470.##5. Halder P, Pal U, Ganguly A, Ghosh P, Ray A, Sarkar S, et al. Genetic aetiology of Down syndrome birth: Novel variants of maternal DNMT3B and RFC1 genes increase risk of meiosis II nondisjunction in the oocyte. Mol Genet Genomics 2023; 298: 293-313.##6. Yi K, Ma Y-H, Wang W, Zhang X, Gao J, He S-E, et al. The roles of reduced folate carrier-1 (RFC1) A80G (rs1051266) polymorphism in congenital heart disease: A meta-analysis. Med Sci Monit 2021; 27: e929911.##7. Romano M, Marcucci R, Buratti E, Ayala YM, Sebastio G, Baralle FE. Regulation of 3′ splice site selection in the 844ins68 polymorphism of the cystathionine β-synthase gene. J Biol Chem 2002; 277: 43821-43829.##8. ElGindy HA, Kotb MA, Mohamed MF, Abuelhamd WA, Alsabagh NN, Anis N, et al. Non-disjunction of chromosome 21 in the young mother at conception. Pediatric Sci J 2022; 2: 164-169.##9. Gelineau‐van Waes J, Heller S, Bauer LK, Wilberding J, Maddox JR, Aleman F, et al. Embryonic development in the reduced folate carrier knockout mouse is modulated by maternal folate supplementation. Birth Defects Res A Clin Mol Teratol 2008; 82: 494-507.##10. Chango A, Emery-Fillon N, de Courcy GP, Lambert D, Pfister M, Rosenblatt DS, et al. A polymorphism (80G-> A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Mol Genet Metab 2000; 70: 310-315.##11. Imani MM, Mozaffari HR, Sharifi R, Sadeghi M. Polymorphism of reduced folate carrier 1 (A80G) and non-syndromic cleft lip/palate: A systematic review and meta-analysis. Arch Oral Biol 2019; 98: 273-279.##12. Scala I, Granese B, Sellitto M, Salomè S, Sammartino A, Pepe A, et al. Analysis of seven maternal polymorphisms of genes involved in homocysteine/folate metabolism and risk of Down syndrome offspring. Genet Med 2006; 8: 409-416.##13. Farjadian Sh, Ota M, Inoko H, Ghaderi A. The genetic relationship among Iranian ethnic groups: An anthropological view based on HLA class II gene polymorphism. Mol Biol Rep 2009; 36: 1943-1950.##14. Fernandes DM, Mittnik A, Olalde I, Lazaridis I, Cheronet O, Rohland N, et al. The spread of steppe and Iranian-related ancestry in the islands of the western Mediterranean. Nat Ecol Evol 2020; 4: 334-345.##15. Suresh RV, Udupa AS, Lingaiah K, Polapalli SK, Ramachandra NB. Association of RFC1 A80G gene polymorphism with advanced maternal age in risk of Down syndrome. Cur Med Res Pract 2017; 7: 6-10.##16. Chaubey G, Ayub Q, Rai N, Prakash S, Mushrif-Tripathy V, Mezzavilla M, et al. “Like sugar in milk”: Reconstructing the genetic history of the Parsi population. Genome Biol 2017; 18: 110.##17. Turkyilmaz A, Simsek S, Diclehan O, Tekeş S, Hilmi I. Cystathionine synthase T833C/844ins68 Polymorphism: A family-based study on down syndromes children. Int Arch Med Res 2011; 2: 54-56.##18. Tsai MY, Bignell M, Schwichtenberg K, Hanson NQ. High prevalence of a mutation in the cystathionine beta-synthase gene. Am J Hum Genet 1996; 59: 1262-1267.##19. Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: A HuGE review. Am J Epidemiol 2004; 159: 423-443.##20. Franco R, Maffei F, Lourenço D, Piccinato C, Morelli V, Thomazini I, et al. The frequency of 844ins68 mutation in the cystathionine beta-synthase gene is not increased in patients with venous thrombosis. Haematologica 1998; 83: 1006-1008.##21. Dutta S, Sinha S, Chattopadhyay A, Gangopadhyay PK, Mukhopadhyay J, Singh M, et al. Cystathionine β-synthase T833C/844INS68 polymorphism: A family-based study on mentally retarded children. Behav Brain Funct 2005; 1: 25.##22. Senemar S, Doroudchi M, Pezeshki AM, Bazrgar M, Torab-Jahromi A, Ghaderi A. Frequency of cystathionine β-synthase 844INS68 polymorphism in Southern Iran. Mol Biol Rep 2009; 36: 353-356.##23. Fintelman-Rodrigues N, Corrêa J, Santos J, Pimentel M, Santos-Rebouças C. Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome. Dis Markers 2009; 26: 155-161.##24. Chango A, Fillon-Emery N, Mircher C, Bléhaut H, Lambert D, Herbeth B, et al. No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers. Br J Nutr 2005; 94: 166-169.##25. Izci Ay O, Ay ME, Erdal ME, Cayan F, Tekin S, Soylemez F, et al. Folate metabolism gene polymorphisms and risk for down syndrome offspring in Turkish women. Genet Test Mol Biomarkers 2015; 19: 191-197.##26. Desai M, Chauhan J. Analysis of polymorphisms in genes involved in folate metabolism and its impact on Down syndrome and other intellectual disability. Meta Gene 2017; 14: 24-29.##27. Biselli JM, Brumati D, Frigeri VF, Zampieri BL, Goloni-Bertollo EM, Pavarino-Bertelli ÉC. Polimorfismos do gene carregador de folato reduzido (RFC1) A80G e transcobalamina 2 (TC2) C776G na etiologia da síndrome de Down. Sao Paulo Med J 2008; 126: 329-332.##28. Neagos D, Cretu R, Tutulan-Cunita A, Stoian V, Bohiltea LC. RFC-1 gene polymorphism and the risk of Down syndrome in romanian population. Maedica 2010; 5: 280-285.##29. Lie RT, Heuch I, Irgens LM. A temporary increase of Down syndrome among births of young mothers in Norway: An effect of risk unrelated to maternal age? Genet Epidemiol 1991; 8: 217-230.##30. Migliore L, Migheli F, Coppedè F. Susceptibility to aneuploidy in young mothers of Down syndrome children. Sci World J 2009; 9: 1052-1060.##31. Kaur A, Kaur A. Role of folate metabolizing genes and homocysteine in mothers of Down syndrome children. Tzu Chi Med J 2022; 34: 456-461.## ##

Analysis of single umbilical artery with concurrent congenital anomaly: Is it a risk factor for poor prognosis? A cross-sectional study تجزیه و تحلیل وجود شریان نافی منفرد با ناهنجاری مادرزادی همزمان: آیا این یک عامل خطر برای پیش‌آگهی ضعیف است؟ یک مطالعه مقطعی 2 1 مقدمه: یک شریان نافی منفرد (SUA) ممکن است با یک ناهنجاری منفرد یا چندین ناهنجاری مادرزادی همراه باشد. اگرچه ناهنجاری­های مرتبط با SUA به صورت اولیه می­توانند باعث مرگ و میر پری­ناتال بالا شوند، اما اهمیت بالینی آنها ارزیابی نشده است. هدف: ما رابطه بین ویژگی­های بالینی و نوع یا تعداد ناهنجاری­های همزمان در نوزادان مبتلا به SUA را بررسی کردیم. مواد و روش­ ها: در این مطالعه مقطعی، 104 نوزاد مبتلا به SUA از ژانویه 2000 تا دسامبر 2020 در بیمارستان Dongsan، Daegu، کره جنوبی وارد مطالعه شدند. اطلاعات مربوط به شرح حال مادر در حامگی و مشخصات دموگرافیک نوزاد، سیر بالینی، تجزیه و تحلیل کروموزومی و ناهنجاری­های مادرزادی جمع­آوری شد. نتایج: از میان نوزادان مبتلا به SUA، 77 نفر (0/%74) یک یا چند ناهنجاری مادرزادی داشتند. ناهنجاری­ها در 66 نفر (5/%63) قلبی، 20 نفر (2/%19) تناسلی، 12 نفر (5/%11) در دستگاه گوارش، 5 نفر (8/%4) در سیستم عصبی مرکزی، 12 نفر (5/%11) اسکلتی و 5 نفر (8/%4) آنومالی­های صورت بودند. تعداد ناهنجاری­های همزمان از 0 تا 4 متغیر بود. نوزادان مبتلا به SUA و ناهنجاری­های گوارشی همزمان، شیوع بالایی از تهویه مثبت اولیه، لوله­گذاری و مصرف داروی اینوتروپیک و نمره آپگار پایین­تر در دقیقه 1 و 5 را داشتند. 7 (7/%6) نوزاد مبتلا به SUA فوت کردند. وزن کم هنگام تولد (نسبت شانس = 16/6،   05/0 = p)، چند فرزندی مادر (41/2، 13/0 = p)، ناهنجاری گوارشی (06/5، 11/0 = p) و احیای اولیه قلبی (77/7، 11/0 = p) عوامل خطر مرگ و میر در نوزادان مبتلا به SUA بودند. نتیجه ­گیری: نوزادان مبتلا به SUA و ناهنجاری‌های گوارشی همزمان، وزن کم هنگام تولد، چند فرزندی مادر و احیای اولیه قلبی پیامدهای ضعیفی داشتند. کلمات کلیدی: شریان نافی منفرد، ناهنجاری­های مادرزادی، پری ناتال مورتالیتی. 2 Background: A single umbilical artery (SUA) may coexist with a single anomaly or multiple congenital anomalies. Although anomalies associated with SUA can primarily cause high perinatal mortality, their clinical significance has not been evaluated. Objective: We investigated the relationship between the clinical features and the type or number of concurrent anomalies in neonates with SUA. Materials and Methods: In this cross-sectional study, 104 neonates with SUA were enrolled from January 2000 to December 2020 at Dongsan hospital, Daegu, South Korea. Data on the maternal history and the neonates demographic characteristics, clinical course, chromosomal analysis, and congenital anomalies, were collected. Results: Among the neonates with SUA included, 77 (74.0%) had one or more congenital anomalies; 66 (63.5%) were cardiac, 20 (19.2%) were genitourinary, 12 (11.5%) were gastrointestinal, 5 (4.8%) were central nervous system, 12 (11.5%) were skeletal, and 5 (4.8%) were facial anomalies. The number of concurrent anomalies ranged from 0-4. Neonates with SUA and concurrent gastrointestinal anomaly had a high incidence of initial positive ventilation, intubation, and inotropic drug use and lower Apgar score at 1 min and 5 min. 7 (6.7%) neonates with SUA died. Low birth weight (odds ratio = 6.16, p = 0.05), maternal multiparity (2.41, p = 0.13), gastrointestinal anomaly (5.06, p = 0.11), and initial cardiac resuscitation (7.77, p = 0.11) were risk factors for mortality in neonates with SUA. Conclusion: Neonates with SUA and concurrent gastrointestinal anomaly, low birth weight, maternal multiparity, and initial cardiac resuscitation had poor outcomes. 139 148 2023/10/12023/04/62023/09/252023/02/202022/09/5 1401/6/14 2024/02/72024/01/172024/03/52024/02/32024/02/2 1402/11/13 Na Hyun Lee Na Hyun Lee Department of Pediatrics, Keimyung University School of Medicine, Daegu, Republic of Korea. کره us22382@naver.com Hee Joung Choi Hee Joung Choi Department of Pediatrics, Keimyung University School of Medicine, Daegu, Republic of Korea. کره joung-756@hanmail.net Single umbilical artery Congenital abnormalities Perinatal mortality. شریان نافی منفرد ناهنجاری­های مادرزادی پری ناتال مورتالیتی. 1. Nayak SS, Shukla A, Girisha KM. Anomalies associated with single umbilical artery at perinatal autopsy. Indian Pediatr 2015; 52: 73-74.##2. Vafaei H, Rafeei Kh, Dalili M, Asadi N, Seirfar N, Akbarzadeh-Jahromi M. Prevalence of single umbilical artery, clinical outcomes and its risk factors: A cross-sectional study. Int J Reprod BioMed 2021; 19: 441-448. ##3. Mailath-Pokorny M, Worda K, Schmid M, Polterauer S, Bettelheim D. Isolated single umbilical artery: Evaluating the risk of adverse pregnancy outcome. Eur J Obstet Gynecol Reprod Biol 2015; 184: 80-83.##4. Xu Y, Ren L, Zhai S, Luo X, Hong T, Liu R, et al. Association between isolated single umbilical artery and perinatal outcomes: A meta-analysis. Med Sci Monit 2016; 22: 1451-1459.##5. Gutvirtz G, Walfisch A, Beharier O, Sheiner E. Isolated single umbilical artery is an independent risk factor for perinatal mortality and adverse outcomes in term neonates. Arch Gynecol Obstet 2016; 294: 931-935.##6. Li T-G, Wang G, Xie F, Yao J-M, Yang L, Wang M-L, et al. Prenatal diagnosis of single umbilical artery and postpartum outcome. Eur J Obstet Gynecol Reprod Biol 2020; 254: 6-10.##7. Dagklis T, Siargkas A, Apostolopoulou A, Tsakiridis I, Mamopoulos A, Athanasiadis A, et al. Adverse perinatal outcomes following the prenatal diagnosis of isolated single umbilical artery in singleton pregnancies: A systematic review and meta-analysis. J Perinat Med 2021; 50: 244-252.##8. Friebe-Hoffmann U, Hiltmann A, Friedl TWP, Lato K, Hammer R, Janni W, et al. Prenatally diagnosed single umbilical artery (SUA)-retrospective analysis of 1169 fetuses. Ultraschall Med 2019; 40: 221-229.##9. Thummala MR, Raju TN, Langenberg P. Isolated single umbilical artery anomaly and the risk for congenital malformations: A meta-analysis. J Pediatr Surg 1998; 33: 580-585.##10. Murphy-Kaulbeck L, Dodds L, Joseph KS, Van den Hof M. Single umbilical artery risk factors and pregnancy outcomes. Obstet Gynecol 2010; 116: 843-850.##11. Csécsei K, Kovács T, Hinchliffe SA, Papp Z. Incidence and associations of single umbilical artery in prenatally diagnosed malformed, midtrimester fetuses: A review of 62 cases. Am J Med Genet 1992; 43: 524-530.##12. Arcos-Machancoses JV, Marín-Reina P, Romaguera-Salort E, García-Camuñas Y, Pérez-Aytés A, Vento M. Postnatal development of fetuses with a single umbilical artery: Differences between malformed and non-malformed infants. World J Pediatr 2015; 11: 61-66. ##13. Lubinsky M. The VACTERL association: Mosaic mitotic aneuploidy as a cause and a model. J Assist Reprod Genet 2019; 36: 1549-1554. ##14. Firth D. Bias reduction of maximum likelihood estimates. Biometrika 1993; 80: 27-38.##15. Benirschke K, Brown WH. A vascular anomaly of the umbilical cord; the absence of one umbilical artery in the umbilical cords of normal and abnormal fetuses. Obstet Gynecol 1955; 6: 399-404. ##16. Kim HJ, Kim JH, Chay DB, Park JH, Kim MA. Association of isolated single umbilical artery with perinatal outcomes: Systemic review and meta-analysis. Obstet Gynecol Sci 2017; 60: 266-273.##17. Mitchell SE, Reidy K, Da Silva Costa F, Palma-Dias R, Cade TJ, Umstad MP. Congenital malformations associated with a single umbilical artery in twin pregnancies. Twin Res Hum Genet 2015; 18: 595-600.##18. Lubinsky M. Embryonic hypocellularity, blastogenetic malformations, and fetal growth restriction. Am J Med Genet A 2017; 173: 151-156.##19. Ahn JH, Choi HJ. Accompanied anomalies in anal atresia or tracheo-esophageal fistula: Comparison with or without VACTERL association. Birth Defects Res 2021; 113: 696-701.##20. Ebbing C, Kessler J, Moster D, Rasmussen S. Single umbilical artery and risk of congenital malformation: Population-based study in Norway. Ultrasound Obstet Gynecol 2020; 55: 510-515. ##21. Luo X, Zhai S, Shi N, Li M, Cui S, Xu Y, et al. The risk factors and neonatal outcomes of isolated single umbilical artery in singleton pregnancy. Sci Rep 2017; 7: 7396.##22. Malova J, Bohmer D, Luha J, Pastorakova A, Cierna Z, Braxatorisova T. Single umbilical artery and reproduction losses in Slovak population: Relation to karyotype and fetal anomalies. Bratisl Lek Listy 2018; 119: 330-334.##23. Heifetz SA. Single umbilical artery. A statistical analysis of 237 autopsy cases and review of the literature. Perspect Pediatr Pathol 1984; 8: 345-378. ##24. Dagklis T, Defigueiredo D, Staboulidou I, Casagrandi D, Nicolaides KH. Isolated single umbilical artery and fetal karyotype. Ultrasound Obstet Gynecol 2010; 36: 291-295.##25. Martínez-Payo C, Cabezas E, Nieto Y, Ruiz de Azúa M, García-Benasach F, Iglesias E. Detection of single umbilical artery in the first trimester ultrasound: Its value as a marker of fetal malformation. Biomed Res Int 2014; 2014: 548729.##26. de Boom ML, Kist-van Holthe JE, Sramek A, Lardenoye SWJ, Walther FJ, Lopriore E. Is screening for renal anomalies warranted in neonates with isolated single umbilical artery? Neonatology 2010; 97: 225-227.##27. Tai C, Conner T, Pevyandi S, Moon-Grady AJ. Prevalence of congenital heart disease in an isolated single umbilical artery is low at a tertiary referral center. J Ultrasound Med 2021; 40: 1729-1730. ##28. Blum M, Weintraub AY, Baumfeld Y, Rotem R, Pariente G. Perinatal outcomes of small for gestational age neonates born with an isolated single umbilical artery. Front Pediatr 2019; 7: 79.## ##

The impact of premenstrual disorders on work disruptions among working women: A cross-sectional study ارتباط اختلالات پیش از قاعدگی و اختلال کار در زنان شاغل: یک مطالعه مقطعی 2 1 مقدمه: علائم فیزیکی و هیجانی در اختلال پیش از قاعدگی سبب افزایش غیبت از کار، کاهش بهره­وری و کاهش کیفیت زندگی مرتبط با کار می­شود. هدف: با توجه به شیوع نسبتا بالای اختلالات پیش از قاعدگی در ایران و مطالعات محدود در زمینه مشکلات ناشی از کار، این مطالعه به بررسی رابطه بین اختلالات پیش از قاعدگی و عملکرد کاری در زنان شاغل پرداخته است. مواد و روش ­ها: این مطالعه مقطعی بر روی 358 زن شاغل (معلم ها و کارگران) در شهر یزد- ایران، از اسفند 1396 تا خرداد 1397 انجام شد. داده­ها با استفاده از پرسشنامه های ابزار غربالگری علائم قبل از قاعدگی، بهره­وری کار و اختلال در فعالیت (نسخه اصلاح شده) و ظرفیت کار عملکردی جمع­آوری گردید. زنان به دو گروه با و بدون سندرم پیش از قاعدگی طبقه­بندی شدند. پیامدهای کاری شامل بهره­وری، ظرفیت کاری و توانایی انجام فعالیت روزانه بین گروه­ها مقایسه گردید. نتایج: در میان 358 شرکت­کننده، (8/%33) 121 زن اختلال قاعدگی داشتند. میزان شیوع سندروم پیش از قاعدگی به­طور قابل توجهی در معلم­ها بیشتر از کارگران (به ترتیب 41/0% در مقابل 7/24%) بوده است (002/0=p ). نمره پیامدهای کار به طور قابل توجه در گروه با سندرم پیش از قاعدگی از گروه دیگر و همچنین در معلم­ها نیز نسبت به کارگران بدتر بود (001/0 >p ). نتیجه­ گیری: این مطالعه وجود همراهی قابل توجه بین علائم پیش از قاعدگی و بهره­وری، ظرفیت عملکرد کاری و توانایی انجام کار روزانه را نشان داد. معلم­ها شیوع بالاتری از سندرم پیش از قاعدگی و عملکرد کاری بدتری نسبت به کارگران داشتند که می­تواند ناشی از سطح تحصیلات بالاتر، استرس کاری، وظایف پیچیده­تر و مسئولیت شغلی بیشتر در معلم­ها باشد. کلمات کلیدی: سندرم پیش از قاعدگی،  اختلال پیش از قاعدگی، عملکرد کاری، زنان شاغل، بهره­وری. 2 Background: Physical and emotional manifestations of premenstrual disorder cause increased absenteeism, decreased productivity, and decreased work-related quality of life. Objective: Due to the relatively high prevalence of premenstrual disorders in Iran and limited studies on its work-related problems, this study investigated the relationship between premenstrual disorders and work performance in working women. Materials and Methods: This cross-sectional study was conducted on 358 working women (teachers and industrial workers) in Yazd, Iran, from July 2019 to January 2020. Data were collected using premenstrual symptom screening tool, the work productivity and activity impairment (a modified version), and functional work capacity questionnaires. Women were classified into 2 groups: women with and without premenstrual disorders. Productivity, functional capacity, and ability to perform activities of daily living were compared between groups. Results: Among 358 participants, 121 women (33.8%) had premenstrual disorders. The prevalence of premenstrual disorders was significantly higher in teachers than workers (0.41% vs. 24.7%, respectively) (p = 0.002). The work results showed a worse score in the group with premenstrual disorder than the other group and teachers compared to workers (p < 0.001). Conclusion: This study showed a significant association between premenstrual disorders and worse work productivity, functional work capacity, and ability to perform activities of daily living. Teachers had a higher prevalence of premenstrual disorders and worse work performance than workers, which can be due to higher education levels, work stress, more complex tasks, and increased work responsibility in teachers. 149 156 2023/10/12023/04/62023/09/252023/02/202022/09/52022/09/15 1401/6/24 2024/02/72024/01/172024/03/52024/02/32024/02/22024/02/4 1402/11/15 Ziba Loukzadeh Ziba Loukzadeh Industrial Diseases Research Center, Center of Excellence for Occupational Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران dr.loukzadeh@gmail.com Nazila Eslamy Nazila Eslamy Industrial Diseases Research Center, Center of Excellence for Occupational Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران dr.n.esl.1985@gmail.com Marziyeh Dehghan Marziyeh Dehghan Industrial Diseases Research Center, Center of Excellence for Occupational Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران marziyeh.dehghan@gmail.com Amir Houshang Mehrparvar Amir Houshang Mehrparvar Industrial Diseases Research Center, Center of Excellence for Occupational Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ایران ah.mehrparvar@gmail.com Premenstrual syndrome Premenstrual dysphoric disorder Work performance Working women Productivity. سندرم پیش از قاعدگی اختلال پیش از قاعدگی عملکرد کاری زنان شاغل بهره­وری. 1. Hardy C, Hunter MS. Premenstrual symptoms and work: Exploring female staff experiences and recommendations for workplaces. Int J Environ Res Public Health 2021; 18: 3647.##2. Ranjbaran M, Omani Samani R, Almasi-Hashiani A, Matourypour P, Moini A. Prevalence of premenstrual syndrome in Iran: A systematic review and meta-analysis. Int J Reprod BioMed 2017; 15: 679-686.##3. Kahyaoglu Sut H, Mestogullari E. Effect of premenstrual syndrome on work-related quality of life in Turkish nurses. Saf Health Work 2016; 7: 78-82.##4. Schoep ME, Adang EMM, Maas JWM, De Bie B, Aarts JWM, Nieboer TE. Productivity loss due to menstruation-related symptoms: A nationwide cross-sectional survey among 32 748 women. BMJ Open 2019; 9: e026186.##5. Meers JM, Nowakowski S. Sleep, premenstrual mood disorder, and women’s health. Curr Opin Psychol 2020; 34: 43-49.##6. Shaheen AA, Aljohani NA, Al-Raddadi RM. Premenstrual syndrome among female doctors at King Fahad Armed Forces Hospital: Prevalence and impact on work, Jeddah, 2014. Int J Med Res Prof 2016; 2: 135-140.##7. Lee W, Lee S, Ahn J, Lee RS, Kang S-K. Premenstrual syndrome incidence rate and risk factors among the working population in the Republic of Korea: A prospective cohort study. BMC Womens Health 2022; 22: 1-8.##8. Kharabah RM, Aljohani ASE, Amara KhA. Prevalence of premenstrual syndrome and its influence on job performance among nurses. Int J Cur Res Rev 2021; 13: 9-15.##9. Chen Y, Yang X, Li X, Wei X, Bai L. Factors associated with premenstrual syndrome of emergency nurse: A multicenter study in China. Gynecol Obstet Clin Med 2022; 2: 199-202.##10. Hannani S, Ghanbary Nekoo N, Nasiri Ziba F, Hosseini AF. The prevalence of premenstrual syndrome and its influential factors in operating room technologists. Iran J Nurs 2019; 32: 67-77.##11. Sulistiyani F, Seweng A, Tahir AM, Russeng SS, Moedhiono AI, Masni. The psychic complaints of premenstrual syndrome with female workers’ productivity in Makassar. East Afr Scholars Multidiscip Bull 2019; 2: 166-168.##12. Ponzo S, Wickham A, Bamford R, Radovic T, Zhaunova L, Peven K, et al. Menstrual cycle-associated symptoms and workplace productivity in US employees: A cross-sectional survey of users of the Flo mobile phone app. Digital Health 2022; 8: 20552076221145852.##13. Ram H, Zalat MM, Sadek SM, Soliman BS, Ahmad RA, Mahdy RS, et al. Premenstrual syndrome and work among female academic teaching staff in a governmental faculty of medicine in Egypt. Egypt J Occupat Med 2017; 41: 35-53.##14. Schmelzer K, Ditzen B, Weise C, Andersson G, Hiller W, Kleinstäuber M. Clinical profiles of premenstrual experiences among women having premenstrual syndrome (PMS): Affective changes predominate and relate to social and occupational functioning. Health Care Women Int 2015; 36: 1104-1123.##15. Read JR, Perz J, Ussher JM. Ways of coping with premenstrual change: Development and validation of a premenstrual coping measure. BMC Womens Health 2014; 14: 1.##16. Kumari S, Sachdeva A. Patterns and predictors of premenstrual symptoms among females working in a psychiatry hospital. Scientifica 2016; 2016: 6943852.##17. Hardy C, Hardie J. Exploring premenstrual dysphoric disorder (PMDD) in the work context: A qualitative study. J Psychosom Obstet Gynecol 2017; 38: 292-300.##18. Saglam HY, Orsal O. Effect of exercise on premenstrual symptoms: A systematic review. Complement Ther Med 2020; 48: 102272.##19. Jasuja V, Purohit G, Mendpara S, Palan BM. Evaluation of psychological symptoms in premenstrual syndrome using PMR technique. J Clin Diagn Res 2014; 8: BC01.## ##

Ruptured ovarian ectopic pregnancy in a primigravid woman: A case report حاملگی خارج رحمی تخمدانی پاره شده در یک زن نخست زا: گزارش یک مورد 2 1 مقدمه: بارداری خارج رحمی تخمدانی یکی از اشکال نادر بارداری خارج رحمی است که در حال گسترش است. استفاده از ابزارهای ضد بارداری داخل رحمی و تکنیک­های کمک باروری از مهمترین عوامل خطر بارداری خارج رحمی تخمدانی هستند. علائم بالینی معمولاً یائسگی، درد شکمی و خونریزی واژینال هستند. تشخیص قطعی بارداری خارج رحمی تخمدانی قبل از پارگی یک چالش جدی باقی مانده است و در بیشتر موارد پس از پارگی تشخیص داده می­شود که در این صورت درمان دارویی جایگاهی ندارد و جراحی لازم می­شود. مورد: در اینجا، ما یک زن 35 ساله نخست­زا را که با درد شکمی و از دست دادن ناگهانی هوشیاری به بیمارستان شهید صدوقی، یزد، ایران مراجعه کرده بود، گزارش می­کنیم. ارزیابی اولیه انجام شد و او تحت لاپاروتومی قرار گرفت. نتیجه­ گیری: درمان انتخابی بارداری خارج رحمی تخمدانی عمل جراحی رزکشن ساک حاملگی بصورت کامل همراه با حفظ بافت تخمدان تا جای ممکن است. با این حال، برخی از موارد، مثل کیس مطرح شده، نیاز به افورکتومی به صورت کامل یا پارشیال می­باشد. کلمات کلیدی: حاملگی خارج رحمی، حاملگی، تخمدان، لاپاراتومی. 2 Background: Ovarian ectopic pregnancy (EP) is one of the rare forms of EP. The use of intrauterine devices and assisted reproduction techniques are among the most important risk factors for ovarian EP. Clinical signs are usually menopause, abdominal pain, and vaginal bleeding. Definitive diagnosis of ovarian EP before its rupture remains a serious challenge and, in most cases, it is diagnosed after rupture when medical treatment has no place and surgery becomes necessary. Case Presentation: Here, we report a 35-yr-old primigravida woman referred to Shahid Sadoughi hospital, Yazd, Iran with abdominal pain and sudden loss of consciousness. An initial evaluation was done and she underwent laparotomy. Conclusion: The preferred treatment for ovarian EP is to surgically remove the gestational sac and preserve as much ovarian tissue as possible. However, some cases, like ours, need a complete or partial oophorectomy. 157 160 2023/10/12023/04/62023/09/252023/02/202022/09/52022/09/152023/12/9 1402/9/18 2024/02/72024/01/172024/03/52024/02/32024/02/22024/02/42024/02/21 1402/12/2 Fahimeh sadat Tabatabaei Mirokabad Fahimeh sadat Tabatabaei Mirokabad Department of Gynecology and Obstetrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران tabatabaie.fahimeh@yahoo.com Mohammad Poorebrahimi Mohammad Poorebrahimi Department of Gynecology and Obstetrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران Mohammadpoorebrahimi@yahoo.com Sajad Zare Garizi Sajad Zare Garizi Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران sajadzare828@gmail.com Razieh sadat Tabatabaei Razieh sadat Tabatabaei Department of Gynecology and Obstetrics, Shahid Sadoughi Uiversity of Medical Sciences, Yazd, Iran. Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران dr.r.tabatabaee@gmail.com Ectopic pregnancy Pregnancy Ovarian Laparotomy. حاملگی خارج رحمی حاملگی تخمدان لاپاراتومی. 1. Kubiaczyk F, Suchocki S, Puskarz R, Zaborowski A, Zaranek K. [Bilateral tubal ectopic pregnancy in a spontaneous cycle: A case report]. Ginekol Pol 2014; 85: 633-634. (in Polish)##2. Szadok P, Kubiaczyk F, Bajorek A, Suchocki S. Ovarian ectopic pregnancy. Ginekol Pol 2019; 90: 728.##3. Sindiani AM, Alshdaifat E, Obeidat B, Obeidat R, Rawashdeh H, Yaseen H. The use of single dose methotrexate in the management of ectopic pregnancy and pregnancy of unknown location: 10 years' experience in a teritary center. Int J Womens Health 2020; 12: 1232-1239.##4. BeGum J, Pallavee P, Samal S. Diagnostic dilemma in ovarian pregnancy: A case series. J Clin Diagn Res 2015; 9: QR01-03.##5. Conner EV, Huber3rd WJ, Matteson KA. Ovarian ectopic pregnancy contralateral to unicornuate uterus. Clin Obstet Gynecol Reprod Med 2015; 1: 66-67.##6. Sotelo C. Ovarian ectopic pregnancy: A clinical analysis. J Nurse Pract 2019; 15: 224-227.##7. Ren F, Liu G, Wang T, Li M, Guo Z. Unruptured ovarian ectopic pregnancy: Two case reports and literature review. Front Physiol 2022; 13: 1036365.##8. Ghasemi Tehrani H, Hamoush Z, Ghasemi M, Hashemi L. Ovarian ectopic pregnancy: A rare case. Iran J Reprod Med 2014; 12: 281-284.##9. Ciortea R, Costin N, Chiroiu B, Mălutan A, Mocan R, Hudacsko A, et al. Ovarian pregnancy associated with pelvic adhesions. Clujul Med 2013; 86: 77-80.##10. Hendriks E, Rosenberg R, Prine L. Ectopic pregnancy: Diagnosis and management. Am Fam Physician 2020; 101: 599-606.##11. Pagidas K, Frishman GN. Nonsurgical management of primary ovarian pregnancy with transvaginal ultrasound-guided local administration of methotrexate. J Minim Invasive Gynecol 2013; 20: 252-254.##12. Stein MW, Ricci ZJ, Novak L, Roberts JH, Koenigsberg M. Sonographic comparison of the tubal ring of ectopic pregnancy with the corpus luteum. J Ultrasound Med 2004; 23: 57-62.##13. Kraemer B, Kraemer E, Guengoer E, Juhasz-Boess I, Solomayer E-F, Wallwiener D, et al. Ovarian ectopic pregnancy: Diagnosis, treatment, correlation to Carnegie stage 16 and review based on a clinical case. Fertil Steril 2009; 92: 392. ##14. Lee R, Dupuis C, Chen B, Smith A, Kim YH. Diagnosing ectopic pregnancy in the emergency setting. Ultrasonography 2018; 37: 78-87.##15. Juan Y-C, Wang P-H, Chen C-H, Ma P-C, Liu W-M. Successful treatment of ovarian pregnancy with laparoscopy-assisted local injection of etoposide. Fertil Steril 2008; 90: 1200.## ##

Molar cesarean scar ectopic pregnancy: Report of 2 cases with review of literature بارداری مولار خارج رحمی اسکار سزارین: توصیف دو مورد و مرور مقالات 2 1 مقدمه: وقوع مول هیداتیفورم در محل اسکار سزارین یافته­ای بسیار نادر است. موارد کمی در مقالات گزارش شده بنابراین اطلاعات کافی در مورد تشخیص و مدیریت درمانی این عارضه موجود نیست. مورد: ما در اینجا دو مورد مول مهاجم با نفوذ به بافت اسکار سزارین گزارش می­کنیم. یکی با شکایت از درد گهگاهی ناحیه هایپوگاستر و تهوع و دیگری با  لکه­بینی مراجعه کرده بودند. هر دو سابقه سزارین داشتند. سونوگرافی ترانس واژینال و سطح خونی بالای بتا­ اچ­ سی ­جی مطرح­کننده بارداری مولار در اسکار سزارین بود و تشخیص با بررسی بافت­شناسی تأیید شد. در مورد اول تخلیه بارداری مولار و به دنبال آن برداشتن اسکار در محل سزارین موجب درمان موفقیت­آمیز با حفظ باروری شد. نتیجه­ گیری: وجود درد شکمی و خونریزی غیرقابل توجیه در یک خانم باردار بدون وجود ساک بارداری در بررسی سونوگرافی قویا مطرح­کننده بارداری خارج رحمی است. روش­های تشخیصی دیگر برای قطعی کردن تشخیص باید استفاده شوند که شامل تیتراژ بتا ­اچ­ سی­ جی، ارزیابی سونوگرافی (2 و 3 بعدی)، تصویربرداری با رزونانس مغناطیسطی (MRI)، لاپاروسکوپی تشخیصی و نهایتا بیوپسی از ضایعه است. کلمات کلیدی: بارداری در اسکار سزارین، بارداری خارج رحمی، مول هیداتیدیفرم، بارداری مولار. 2 Background: The occurrence of hydatidiform mole at the cesarean scar site is a rare problem. Few cases have been reported, thus there is not enough information for accurate diagnosis and management of this event. Case Presentation: Herein, we present 2 cases of an invasive hydatidiform mole embedded in cesarean scar tissue, one presented with occasional hypogastric pain and nausea and another with spotting both with a history of cesarean section. Transvaginal ultrasonography and a considerably high titer of beta-human chorionic gonadotropin blood test suggested the existence of molar pregnancy on the cesarean scar, which was confirmed through histological assessment. In the first case, evacuation of molar pregnancy followed by scar resection at the cesarean scar site led to successful fertility preservation management. Conclusion: The presence of abdominal pain and unexplained bleeding in a pregnant woman without gestational sac in ultrasonography, strongly suggests ectopic pregnancy. The process of diagnosis should be followed by definitive diagnostic evaluation, including beta-human chorionic gonadotropin titer measurement, ultrasonographic assessment (2 and 3-dimensional), magnetic resonance imaging, diagnostic laparoscopy, and finally biopsy of the lesion. 161 168 2023/10/12023/04/62023/09/252023/02/202022/09/52022/09/152023/12/92023/01/13 1401/10/23 2024/02/72024/01/172024/03/52024/02/32024/02/22024/02/42024/02/212024/01/13 1402/10/23 Sedigheh Hosseinimousa Sedigheh Hosseinimousa Department of Obstetrics and Gynecology and Reproductive, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran. ایران sedighehoseinimosa@gmail.com Saymaz Navaei Saymaz Navaei Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran. ایران saymaznavaei@yahoo.com Marzieh Talebian Marzieh Talebian Department of Obstetrics and Gynecology, Kashan University of Medical Sciences, Shahid Beheshti Hospital, Kashan, Iran. ایران talebianm861@gmail.com Cesarean scar pregnancy Ectopic pregnancy Hydatidiform mole Molar pregnancy. بارداری در اسکار سزارین بارداری خارج رحمی مول هیداتیدیفرم بارداری مولار. 1. Ling Ch, Zhao J, Qi X. Partial molar pregnancy in the cesarean scar: A case report and literature review. Medicine 2018; 97: 26-27.##2. Zhou L-Y, Zhu X-D, Jiang J, Jiang T-A. Uterine mass after caesarean section: A report of two cases. BMC Pregnancy Childbirth 2020; 20: 508-512.##3. Yamada Y, Ohira S, Yamazaki T, Shiozawa T. Ectopic molar pregnancy: Diagnostic efficacy of magnetic resonance imaging and review of the literature. Case Rep Obstet Gynecol 2016; 6: 761-767.##4. Darling A, Albright BB, Strickland KC, Davidson BA. Molar pregnancy: Epidemiology, diagnosis, management, surveillance. Curr Obstet Gynecol Rep 2022; 11: 133-141.##5. Al-Bataineh R, Rawashdeh Sh, Lataifeh LN, Alzghoul SM, Al Sharie AH, Obeidat R, et al. Cesarean scar ectopic partial molar pregnancy: A case report and a review of literature. Case Rep Womens Health 2023; 39: e00555.##6. Calì G, Timor-Tritsch IE, Palacios-Jaraquemada J, Monteaugudo A, Buca D, Forlani F, et al. Outcome of cesarean scar pregnancy managed expectantly: Systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018; 51: 169-175.##7. Antoine C, Young BK. Cesarean section one hundred years 1920-2020: The good, the bad and the ugly. J Perinat Med 2020; 49: 5-16.##8. Biswas R, Saxena P, Gupta U, Choudhary N, Chawla R. Persistent trophoblastic disease at cesarean scar. Kathmandu Univ Med J 2016; 56: 376-379.##9. El Miski F, Touimi Benjelloun A, Bouab M, Lamrissi A, Fichtali K, Bouhya S. Spontaneous uterine rupture during the first trimester of a partial molar pregnancy in a scar uterus: A rare case report. Int J Surg Case Rep 2021; 85: 106229.##10. Jin F-Sh, Ding D-Ch, Wu G-J, Hwang K-Sh. Molar pregnancy in a cesarean section scar of uterus. J Med Sci 2011; 31: 173-176.##11. Wu Ch-F, Hsu Ch-Y, Chen Ch-P. Ectopic molar pregnancy in a cesarean scar. Taiwanese J Obstet Gynecol 2006; 45: 343-345. ##12. Potdar N, Navti OB, McParland P, Khare M, Elson J. Diagnosis and management of ectopic molar caesarean scar pregnancy. Ultrasound Obstet Gynecol 2010; 36 (Suppl.): 231.##13. Vimercati A, de Gennaro AC, Resta L, Cormio G, Cicinelli E. Sonographic and power doppler evaluation of an invasive mole located in a cesarean scar pregnancy. J Ultrasound Med 2016; 35: 1608-1612.##14. Polat I, Yücel B, Davutoglu S, Erdem B, Gedikbasi A. Persistent trophoblastic disease at caesarean scar and its successful treatment with multiple dose systemic methotrexate after suction curettage. J Obstet Gynaecol 2017; 37: 392-394.##15. Dagdeviren EG, Dur R, Fadiloglu E, Demirdag E, Ozturk C, Altay M. Molar pregnancy in cesarean section scar: A case report. Turk J Obstet Gynecol 2017; 14: 249-251.##16. Liu GL, He SC, Shan WJ, Chen HY. Repetitive hydatidiform mole in the cesarean scar: A case report and literature review. Clin Exp Obstet Gynecol 2020; 4: 607-610. ##17. Jiang H-R, Shi W-W, Liang X, Zhang H, Tan Y. Hydatidiform mole in a scar on the uterus: A case report. World J Clin Cases 2020; 26: 1547-1553.##18. Cain A, Breen MT, Holtz M, Williams-Brown MY. Robotic-assisted laparoscopic hysterectomy for management of cesarean scar ectopic concerning for a molar pregnancy. J Minim Invasive Gynecol 2022; 29: S37-S86.##19. Kriplani I, Srivastava V, Bhardwaj K, Jai N, Kriplani A. Laparoscopic management of partial molar caesarean scar ectopic pregnancy. J Minim Invasive Gynecol 2022; 29: 1221-1223.##20. Hfaiedh I, Jaafar W, Mallouli F, Ben Mbarek C, Chiba Y, Khalifa N, et al. A molar pregnancy as a cesarean scar pregnancy: About the ninth case and literature review. Am J Surg Case Rep 2023; 4: 0114-0116.## ##