☆ 4.6 Article

Elevated level of 17β-estradiol is associated with overexpression of FSHR, CYP19A1, and CTNNB1 genes in porcine ovarian follicles after prenatal and neonatal flutamide exposure

THERIOGENOLOGY (2012)

期刊

THERIOGENOLOGY

卷 78, 期 9, 页码 2050-2060

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ELSEVIER SCIENCE INC

DOI: 10.1016/j.theriogenology.2012.07.026

关键词

FSHR; beta-catenin; Aromatase; Flutamide; Ovary; Pig

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Reproductive Biology Veterinary Sciences

资金

DS/MND/WBi [Z/IZ/3/2012]
Jagiellonian University within the SET project
European Union within the European Social Fund

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摘要

Recent studies suggest that disturbed androgen action during gestational and neonatal periods leads to reprogramming of the trajectory of ovarian development, manifested by altered follicular functioning in adulthood. In this study, we tested whether prenatal and neonatal exposure to antiandrogen flutamide affected ovarian 17 beta-estradiol (E-2) synthesis and the associated gene expression in large antral follicles of adult pigs. Flutamide was injected into pregnant gilts between Days 80 and 88 of gestation and into female piglets between Days 2 and 10 postnatally. After animals reached sexual maturity, the ovaries were collected from treated and nontreated (control) pigs. The analysis of E-2 concentration in follicular tissues, as well as FSH and LH levels in plasma of control and flutamide-treated animals were conducted. In addition, the expression of mRNAs and proteins for FSH receptor (FSHR), cytochrome P450 aromatase (CYP19A1) and beta-catenin (CTNNB1) was examined in large antral follicles of adult pigs. The E-2 concentration was greater in response to flutamide administered prenatally (P < 0.05) and neonatally (P < 0.01), whereas there was no changes in plasma gonadotropin concentration. Real-time polymerase chain reaction analysis revealed significant upregulation of FSHR, CYP19A1, and CTNNB1 at the mRNA level after maternal (P < 0.001, P < 0.01, P < 0.05, respectively) and neonatal (P < 0.001, P < 0.001, P < 0.01, respectively) flutamide exposure. The expression of FSHR protein was higher (P < 0.01) only after neonatal exposure to flutamide, whereas CYP19A1 and CTNNB1 proteins were upregulated in response to both prenatal (P < 0.01) and neonatal (P < 0.001) flutamide administration. Furthermore, membranous CTNNB1 immunolocalization indicates that it is not involved in regulation of FSH-mediated CYP19A1 activity as a transcription factor, but rather contributes to the intercellular adhesion. Concluding, it appears that the higher E-2 level in response to flutamide treatments is a result of the intensified aromatization and local E-2 action at the ovary level. The observed changes might influence the normal follicle development and pig fertility as a consequence. (C) 2012 Elsevier Inc. All rights reserved.

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Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries

Morgane Le Rolle, Filippo Massa, Pam Siggers, Laurent Turchi, Agnes Loubat, Bon-Kyoung Koo, Hans Clevers, Andy Greenfield, Andreas Schedl, Marie-Christine Chaboissier, Anne-Amandine Chassot

Summary: This study shows that germ cell-intrinsic beta-catenin activity in mouse embryonic ovaries is essential for maintaining pluripotency and its repression is crucial for differentiation and meiosis entry. The interaction of beta-catenin with the pluripotent-associated factor POU5F1 in the nucleus is associated with germ cell pluripotency, and its exit from the nucleus correlates with germ cell differentiation. These findings highlight the role of beta-catenin as a central gatekeeper in ovarian differentiation and gametogenesis.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)