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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 Dec; 78(9):2050-60.T

Abstract

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 17β-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 β-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.

Authors+Show Affiliations

Department of Endocrinology, Institute of Zoology, Jagiellonian University, Krakow, Poland. malgorzata.durlej@uj.edu.plNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23043943

Citation

Grzesiak, M, et al. "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, vol. 78, no. 9, 2012, pp. 2050-60.
Grzesiak M, Knapczyk-Stwora K, Duda M, et al. 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;78(9):2050-60.
Grzesiak, M., Knapczyk-Stwora, K., Duda, M., & Slomczynska, M. (2012). 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, 78(9), 2050-60. https://doi.org/10.1016/j.theriogenology.2012.07.026
Grzesiak M, et al. 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;78(9):2050-60. PubMed PMID: 23043943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Grzesiak,M, AU - Knapczyk-Stwora,K, AU - Duda,M, AU - Slomczynska,M, Y1 - 2012/10/05/ PY - 2012/07/04/received PY - 2012/07/23/revised PY - 2012/07/29/accepted PY - 2012/10/10/entrez PY - 2012/10/10/pubmed PY - 2013/4/3/medline SP - 2050 EP - 60 JF - Theriogenology JO - Theriogenology VL - 78 IS - 9 N2 - 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 17β-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 β-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. SN - 1879-3231 UR - https://www.unboundmedicine.com/medline/citation/23043943/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0093-691X(12)00442-6 DB - PRIME DP - Unbound Medicine ER -