Effect of Prenatal and Neonatal Anti-Androgen Flutamide Treatment on Aquaporin 5 Expression in the Adult Porcine Ovary

Reprod Domest Anim. 2016 Feb;51(1):105-13. doi: 10.1111/rda.12652. Epub 2015 Dec 10.

Abstract

The growth of ovarian follicles is accompanied by fluid-filled antrum formation. Water movement within the follicular wall is predominantly transcellular via membranous water channels named aquaporins (AQPs). Androgens are important regulators of mammalian folliculogenesis, and their prenatal and/or neonatal deficiency affects female fertility in adulthood. Therefore, this study was performed to determine whether gestational or neonatal exposure to the anti-androgen flutamide influences androgen-dependent AQP5 expression in pre-antral and 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 post-natally. The ovaries were collected from flutamide-treated and non-treated (control) sexually mature pigs. In pre-antral follicles, AQP5 mRNA and protein levels were both downregulated following maternal (p < 0.01 and p < 0.01, respectively) and neonatal (p < 0.01 and p < 0.01, respectively) flutamide exposure. Likewise, the expression of mRNA (p < 0.01 and p < 0.001, respectively) and protein (p < 0.05 and p < 0.01, respectively) for AQP5 were diminished in large antral follicles in both groups. Immunohistochemistry showed decreased intensity of AQP5 immunoreaction in pre-antral (p < 0.01) and large antral (p < 0.001) follicles following flutamide treatment. Moreover, radioimmunological analysis revealed that changes observed in AQP5 expression corresponded with diminished follicular androgens production after both maternal (p < 0.05 and p < 0.05, respectively) and neonatal (p < 0.05 and p < 0.01, respectively) flutamide administration. Therefore, AQP5 appears to be a potential regulator of follicular fluid accumulation, under androgen control, and may be a key factor in antral follicle growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Animals
  • Animals, Newborn*
  • Aquaporin 5 / analysis
  • Aquaporin 5 / genetics*
  • Aquaporin 5 / physiology
  • Female
  • Flutamide / administration & dosage
  • Flutamide / pharmacology*
  • Gene Expression / drug effects
  • Immunohistochemistry
  • Maternal-Fetal Exchange
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / embryology
  • Ovarian Follicle / physiology
  • Ovary / chemistry
  • Ovary / drug effects
  • Ovary / metabolism*
  • Pregnancy
  • RNA, Messenger / analysis
  • Sus scrofa*

Substances

  • Androgen Antagonists
  • Aquaporin 5
  • RNA, Messenger
  • Flutamide