In Vitro Growth and Ovulation of Follicles from Ovaries of Estrogen Receptor (ER)α and ERβ Null Mice Indicate a Role for ERβ in Follicular Maturation

Abstract

AbstractBoth estrogen receptor (ER) α and β are expressed within the ovary and lack of either of these receptors affects ovarian function. In this study, the role of ERα and ERβ in folliculogenesis and ovulation was further analyzed. Evaluation of ovarian follicle populations in wild-type and ERβ knockout (βERKO) ovaries revealed reduced late antral growth and ovulatory capacity of βERKO follicles, indicated by reduced numbers of large antral follicles and corpora lutea and increased atresia of large antral follicles. An in vitro culture system was used to study growth, rupture, and luteinization of wild-type, ERα knockout (αERKO) and βERKO ovarian follicles. αERKO follicles exhibited wild-type-like growth and ovulation rates but an increased capacity to synthesize estradiol. In contrast, βERKO follicles showed a significant lack of progression from early antral to large antral stage, decreased estradiol production, and reduced ovulation. Expression patterns of several genes involved in follicle maturation and ovulation were analyzed in follicles grown in vitro. Ar, Pgr, and Has2 mRNA expression levels were the same among the three genotypes. However, βERKO follicles showed reduced expression of Cyp19 mRNA during follicle maturation and reduced Lhcgr and Ptgs2 mRNA expression after human chorionic gonadotropin stimulus. Luteinization occurs normally in αERKO and βERKO follicles, shown by increased progesterone secretion and increased cdkn1b mRNA expression after human chorionic gonadotropin. Collectively, these data indicate that ERβ, but not ERα, plays a direct role in folliculogenesis. ERβ appears to facilitate follicle maturation from the early antral to the preovulatory stage.