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Submitted on August 23, 2004
Accepted on February 17, 2005
and ER
null mice indicate a role for ER in follicular maturation
Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Biostatistics Branch, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
* To whom correspondence should be addressed. E-mail: korach{at}niehs.nih.gov.
Both estrogen receptor 
and 
(ER and ER) are expressed within the ovary and lack of either of these receptors affects ovarian function. In this study, the role of ER and ER in folliculogenesis and ovulation was further analyzed. Evaluation of ovarian follicle populations in wild-type and ER knockout (ERKO) ovaries revealed reduced late antral growth and ovulatory capacity of ERKO 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, ER knockout (ERKO) and ERKO ovarian follicles. ERKO follicles exhibited wild-type like growth and ovulation rates but an increased capacity to synthesize estradiol. In contrast, ERKO 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, ERKO follicles showed reduced expression of Cyp19 mRNA during follicle maturation and reduced Lhcgr and Ptgs2 mRNA expression after hCG stimulus. Luteinization occurs normally in ERKO and ERKO follicles, shown by increased progesterone secretion and increased cdkn1b mRNA expression after hCG. Collectively, these data indicate that ER, but not ER, plays a direct role in folliculogenesis. ER appears to facilitate follicle maturation from the early antral to the preovulatory stage.
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