The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study
Abstract 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 perf...
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| Format: | Article |
| Language: | English |
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Shahid Sadoughi University of Medical Sciences
2023-01-01
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| Series: | International Journal of Reproductive BioMedicine |
| Subjects: | |
| Online Access: | https://doi.org/10.18502/ijrm.v21i1.12669 |
| _version_ | 1797924696079990784 |
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| author | Zahra Shaaban Amin Derakhshanfar Mohammad Reza Jafarzadeh Shirazi Mohammad Javad Zamiri Javad Moayedi Mahjoob Vahedi Abouzar Valizadeh |
| author_facet | Zahra Shaaban Amin Derakhshanfar Mohammad Reza Jafarzadeh Shirazi Mohammad Javad Zamiri Javad Moayedi Mahjoob Vahedi Abouzar Valizadeh |
| author_sort | Zahra Shaaban |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T15:05:03Z |
| format | Article |
| id | doaj.art-2ac9e364a7ae414f821f181199ac0e42 |
| institution | Directory Open Access Journal |
| issn | 2476-4108 2476-3772 |
| language | English |
| last_indexed | 2024-04-10T15:05:03Z |
| publishDate | 2023-01-01 |
| publisher | Shahid Sadoughi University of Medical Sciences |
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| series | International Journal of Reproductive BioMedicine |
| spelling | doaj.art-2ac9e364a7ae414f821f181199ac0e422023-02-15T05:02:33ZengShahid Sadoughi University of Medical SciencesInternational Journal of Reproductive BioMedicine2476-41082476-37722023-01-01211718210.18502/ijrm.v21i1.12669ijrm.v21i1.12669The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental studyZahra Shaaban0Amin Derakhshanfar1Mohammad Reza Jafarzadeh Shirazi2Mohammad Javad Zamiri3Javad Moayedi4Mahjoob Vahedi5Abouzar Valizadeh6 Department of Animal Sciences, College of Agriculture, Shiraz University, Shiraz, Iran. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Department of Animal Sciences, College of Agriculture, Shiraz University, Shiraz, Iran. Department of Animal Sciences, College of Agriculture, Shiraz University, Shiraz, Iran. 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. Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.Abstract 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.https://doi.org/10.18502/ijrm.v21i1.12669androgens, aromatase inhibitors, rat, sexual activities, testes histopathology. |
| spellingShingle | Zahra Shaaban Amin Derakhshanfar Mohammad Reza Jafarzadeh Shirazi Mohammad Javad Zamiri Javad Moayedi Mahjoob Vahedi Abouzar Valizadeh The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study International Journal of Reproductive BioMedicine androgens, aromatase inhibitors, rat, sexual activities, testes histopathology. |
| title | The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study |
| title_full | The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study |
| title_fullStr | The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study |
| title_full_unstemmed | The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study |
| title_short | The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study |
| title_sort | effects of letrozole induced maternal hyperandrogenism on sexual behaviors testicular histology and serum biochemical traits in male offspring rats an experimental study |
| topic | androgens, aromatase inhibitors, rat, sexual activities, testes histopathology. |
| url | https://doi.org/10.18502/ijrm.v21i1.12669 |
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