Cargando…
The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study
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 o...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Knowledge E
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982319/ https://www.ncbi.nlm.nih.gov/pubmed/36875502 http://dx.doi.org/10.18502/ijrm.v21i1.12669 |
_version_ | 1784900305476911104 |
---|---|
author | Shaaban, Zahra Derakhshanfar, Amin Reza Jafarzadeh Shirazi, Mohammad Javad Zamiri, Mohammad Moayedi, Javad Vahedi, Mahjoob Valizadeh, Abouzar |
author_facet | Shaaban, Zahra Derakhshanfar, Amin Reza Jafarzadeh Shirazi, Mohammad Javad Zamiri, Mohammad Moayedi, Javad Vahedi, Mahjoob Valizadeh, Abouzar |
author_sort | Shaaban, Zahra |
collection | PubMed |
description | 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 [Formula: see text] 0.0001) and reduced litter size (n = 12.25 vs. n = 2, p [Formula: see text] 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 [Formula: see text] 0.0001) and 1.00 mg/kg BW (p [Formula: see text] 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 [Formula: see text] 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. |
format | Online Article Text |
id | pubmed-9982319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Knowledge E |
record_format | MEDLINE/PubMed |
spelling | pubmed-99823192023-03-04 The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study Shaaban, Zahra Derakhshanfar, Amin Reza Jafarzadeh Shirazi, Mohammad Javad Zamiri, Mohammad Moayedi, Javad Vahedi, Mahjoob Valizadeh, Abouzar Int J Reprod Biomed Original Article 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 [Formula: see text] 0.0001) and reduced litter size (n = 12.25 vs. n = 2, p [Formula: see text] 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 [Formula: see text] 0.0001) and 1.00 mg/kg BW (p [Formula: see text] 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 [Formula: see text] 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. Knowledge E 2023-02-08 /pmc/articles/PMC9982319/ /pubmed/36875502 http://dx.doi.org/10.18502/ijrm.v21i1.12669 Text en Copyright © 2023 Shaaban et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Shaaban, Zahra Derakhshanfar, Amin Reza Jafarzadeh Shirazi, Mohammad Javad Zamiri, Mohammad Moayedi, Javad Vahedi, Mahjoob Valizadeh, Abouzar The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study |
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 | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982319/ https://www.ncbi.nlm.nih.gov/pubmed/36875502 http://dx.doi.org/10.18502/ijrm.v21i1.12669 |
work_keys_str_mv | AT shaabanzahra theeffectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT derakhshanfaramin theeffectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT rezajafarzadehshirazimohammad theeffectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT javadzamirimohammad theeffectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT moayedijavad theeffectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT vahedimahjoob theeffectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT valizadehabouzar theeffectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT shaabanzahra effectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT derakhshanfaramin effectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT rezajafarzadehshirazimohammad effectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT javadzamirimohammad effectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT moayedijavad effectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT vahedimahjoob effectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy AT valizadehabouzar effectsofletrozoleinducedmaternalhyperandrogenismonsexualbehaviorstesticularhistologyandserumbiochemicaltraitsinmaleoffspringratsanexperimentalstudy |