Volume 21, Issue 1 (January 2023)                   IJRM 2023, 21(1): 71-82 | Back to browse issues page

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Shaaban Z, Derakhshanfar A, Jafarzadeh Shirazi M R, Zamiri M J, Moayedi J, Vahedi M et al . The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study. IJRM 2023; 21 (1) :71-82
URL: http://ijrm.ir/article-1-2477-en.html
The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study
Zahra Shaaban1 , Amin Derakhshanfar * 2, Mohammad Reza Jafarzadeh Shirazi1 , Mohammad Javad Zamiri1 , Javad Moayedi3 , Mahjoob Vahedi4 , Abouzar Valizadeh4
1- Department of Animal Sciences, College of Agriculture, Shiraz University, Shiraz, Iran.
2- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. , derakhshanfar@sums.ac.ir
3- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
4- Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Abstract:   (1053 Views)
Background: Intrauterine endocrine abnormalities have profound effects on the development of physiological disorders.
Objective: This study aimed to assess the effects of in utero exposure to letrozole (an aromatase inhibitor) and its late consequences on the reproductive and metabolic performance of an adult male offspring.
Materials and Methods: 15 pregnant Sprague-Dawley rats (8 wk, 155 gr) were randomly assigned into 5 experimental groups (n = 3/each) and orally received either letrozole at doses of 0.25, 0.75, 1.00, and 1.25 mg/kg body weight (BW) or vehicle (control) on the gestation days of 16, 17, and 18. Pregnancy outcome, sexual behaviors on postnatal day 60, serum biochemical features, and the histopathology of testes were assessed in male offspring.
Results: Compared to control group, delayed labor (21.83 vs. 24.25, p < 0.0001) and reduced litter size (n = 12.25 vs. n = 2, p < 0.0001) were recorded in 1.25 mg/kg BW group. A reduction in high-density lipoprotein level and the elevation of testes weight, BW gain, anogenital distance, as well as the serum concentrations of testosterone, triglycerides, cholesterol, and glucose were observed in 1.25 mg/kg BW (p < 0.0001) and 1.00 mg/kg BW (p < 0.0001) groups in comparison to control. A larger number of anogenital female sniffing, pursuit, and mounting behaviors were also observed in 1.25 mg/kg BW group in comparison to control (p < 0.0001). Severe testicular defects including necrosis and disruption of the epithelium of seminiferous tubules, sloughing of epithelial cells, and spermatogenesis arrest were observed in letrozole-treated groups, in a dose-dependent manner.
Conclusion: Maternal exposure to letrozole can adversely affect the reproductive and metabolic performance of male offspring rats, suggesting an incomplete sex differentiation.
Keywords: Androgens, Aromatase inhibitors, Rat, Sexual activities, Testes histopathology.
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Type of Study: Original Article | Subject: Reproductive Physiology
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