Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study

Abstract Background: Increased levels of kisspeptin are associated with hypothalamus-pituitary-ovary axis dysfunction. It may lead to the development of polycystic ovary syndrome (PCOS). Objective: We aimed to investigate the effect of prenatal kisspeptin antagonist exposure on the development of PC...

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Main Authors: Elahe Sadeghian Bakhi, Nasim Hayati Roodbari, Morteza Anvari, Fahimeh Ramezani Tehrani
Format: Article
Language:English
Published: Shahid Sadoughi University of Medical Sciences 2023-02-01
Series:International Journal of Reproductive BioMedicine
Subjects:
Online Access:https://doi.org/10.18502/ijrm.v21i2.12801
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author Elahe Sadeghian Bakhi
Nasim Hayati Roodbari
Morteza Anvari
Fahimeh Ramezani Tehrani
author_facet Elahe Sadeghian Bakhi
Nasim Hayati Roodbari
Morteza Anvari
Fahimeh Ramezani Tehrani
author_sort Elahe Sadeghian Bakhi
collection DOAJ
description Abstract Background: Increased levels of kisspeptin are associated with hypothalamus-pituitary-ovary axis dysfunction. It may lead to the development of polycystic ovary syndrome (PCOS). Objective: We aimed to investigate the effect of prenatal kisspeptin antagonist exposure on the development of PCOS in prenatally androgenized rats in adulthood. Materials and Methods: In this experimental study, pregnant rats were injected with free testosterone (T, 5 mg/day) or T+P271 (kisspeptin antagonist) on the 20 th day of the pregnancy period (n = 5 in each group), while rats in the control group received solvent. Female offspring were examined in terms of anogenital distance (AGD), anovaginal distance (AVD), vaginal opening, serum total testosterone (TT) levels, ovarian follicles, and the regularity of estrous cycles in adulthood. AGD and AVD were measured using a vernier caliper. TT levels were measured using the enzyme-linked immunosorbent assay method. Ovaries were fixed in 10% formalin, tissue processing was done by a standard protocol, and then ovaries embedded in paraffin. 5 μm-thickness ovarian sections mounted on a glass slide, deparaffinized, and stained using Harris's Hematoxylin and Eosin Y. Results: AGD, AVD (p < 0.001), TT levels (p = 0.02), and the numbers of preantral and antral follicles (p < 0.001) in the ovaries were significantly decreased in prenatally T-P271-exposed rats compared to prenatally T-exposed rats. The age of vaginal opening was early in T-P271-exposed rats compared to prenatally T-exposed rats (p < 0.001). The number of corpora lutea was significantly increased in T-P271-exposed rats (p < 0.001). No cystic follicles were observed in the ovaries of prenatally T-P271-exposed rats. Prenatally T-P271-exposed rats had regular estrous cycles compared to prenatally T-exposed rats. Conclusion: Prenatal exposure to kisspeptin antagonist can prevent PCOS development in prenatally androgenized rats in adulthood.
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spelling doaj.art-1184ecfeb2c24c9eb6d073a729199ddf2023-04-05T04:56:14ZengShahid Sadoughi University of Medical SciencesInternational Journal of Reproductive BioMedicine2476-41082476-37722023-02-012129911010.18502/ijrm.v21i2.12801ijrm.v21i2.12801Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental studyElahe Sadeghian Bakhi0Nasim Hayati Roodbari1Morteza Anvari2Fahimeh Ramezani Tehrani3 Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran. Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran. Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Abstract Background: Increased levels of kisspeptin are associated with hypothalamus-pituitary-ovary axis dysfunction. It may lead to the development of polycystic ovary syndrome (PCOS). Objective: We aimed to investigate the effect of prenatal kisspeptin antagonist exposure on the development of PCOS in prenatally androgenized rats in adulthood. Materials and Methods: In this experimental study, pregnant rats were injected with free testosterone (T, 5 mg/day) or T+P271 (kisspeptin antagonist) on the 20 th day of the pregnancy period (n = 5 in each group), while rats in the control group received solvent. Female offspring were examined in terms of anogenital distance (AGD), anovaginal distance (AVD), vaginal opening, serum total testosterone (TT) levels, ovarian follicles, and the regularity of estrous cycles in adulthood. AGD and AVD were measured using a vernier caliper. TT levels were measured using the enzyme-linked immunosorbent assay method. Ovaries were fixed in 10% formalin, tissue processing was done by a standard protocol, and then ovaries embedded in paraffin. 5 μm-thickness ovarian sections mounted on a glass slide, deparaffinized, and stained using Harris's Hematoxylin and Eosin Y. Results: AGD, AVD (p < 0.001), TT levels (p = 0.02), and the numbers of preantral and antral follicles (p < 0.001) in the ovaries were significantly decreased in prenatally T-P271-exposed rats compared to prenatally T-exposed rats. The age of vaginal opening was early in T-P271-exposed rats compared to prenatally T-exposed rats (p < 0.001). The number of corpora lutea was significantly increased in T-P271-exposed rats (p < 0.001). No cystic follicles were observed in the ovaries of prenatally T-P271-exposed rats. Prenatally T-P271-exposed rats had regular estrous cycles compared to prenatally T-exposed rats. Conclusion: Prenatal exposure to kisspeptin antagonist can prevent PCOS development in prenatally androgenized rats in adulthood.https://doi.org/10.18502/ijrm.v21i2.12801androgen, kisspeptin antagonist, polycystic ovary syndrome, rat.
spellingShingle Elahe Sadeghian Bakhi
Nasim Hayati Roodbari
Morteza Anvari
Fahimeh Ramezani Tehrani
Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study
International Journal of Reproductive BioMedicine
androgen, kisspeptin antagonist, polycystic ovary syndrome, rat.
title Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study
title_full Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study
title_fullStr Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study
title_full_unstemmed Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study
title_short Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study
title_sort prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally androgenized rats in adulthood an experimental study
topic androgen, kisspeptin antagonist, polycystic ovary syndrome, rat.
url https://doi.org/10.18502/ijrm.v21i2.12801
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