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The role of Brca2 in gametogenesis has been obscure because of embryonic lethality of the knockout mice. We generated Brca2-null mice carrying a human BAC with the BRCA2 gene. This construct rescues embryonic lethality and the mice develop normally. However, there is poor expression of the transgene in the gonads and the mice are infertile, allowing(More)
Although Smad 3 is known to serve as a signaling intermediate for the transforming growth factor beta (TGFbeta) family in nonreproductive tissues, its role in the ovary is unknown. Thus, we used a recently generated Smad 3-deficient (Smad 3-/-) mouse model to test the hypothesis that Smad 3 alters female fertility and regulates the growth of ovarian(More)
OBJECTIVE The purpose of this study was to evaluate whether genetic polymorphisms in selected cytochrome P450 enzymes (CYPc17alpha, CYP1A1, and CYP1B1), estradiol (E2) levels, and estrone levels were associated with hot flushes. METHODS Women with hot flushes were those aged 45-54 years who reported ever experiencing hot flushes (n = 354). Women without(More)
It is believed that the endowment of primordial follicles in mammalian ovaries is finite. Once follicles are depleted, infertility ensues. Thus, the size of the initial endowment has consequences for fertility and reproductive longevity. Follicular endowment is comprised of various processes that culminate with the incorporation of meiosis-arrested oocytes(More)
Little is known about the embryonic factors that regulate the size of the primordial follicle endowment at birth. A few studies suggest that members of the B-cell lymphoma/leukemia-2 (bcl-2) family of protooncogenes may be important determinants. Thus, the purpose of this study was to test whether bcl-2 regulates the size of the primordial follicle pool at(More)
OBJECTIVE This study was undertaken to determine whether body mass index (BMI) is associated with hot flashes and whether the mechanism by which BMI increases the risk of hot flashes is by lowering estrogen levels. STUDY DESIGN A case-control study was conducted among midlife women to examine risk factors for hot flashes. Cases were women who reported(More)
OBJECTIVE Studies suggest that African American women may have a greater risk of hot flashes compared to Caucasian women, but the reasons for this are unknown. This study tested the hypothesis that African American women have an increased risk of hot flashes due to racial differences in risk factors for hot flashes, including high body mass index (BMI) and(More)
Humans are chronically exposed to the plasticizer, Bisphenol A (BPA), that can adversely affect the normal hormonal regulation of cellular functions by mimicking the actions of estrogen. This biological response to BPA may vary according to an individual's genetic characteristics (e.g., BRCA1 mutations or deletion). In this study, both cell culture and(More)
The mammalian ovary contains antral follicles, which are responsible for the synthesis and secretion of hormones that regulate estrous cyclicity and fertility. The organochlorine pesticide methoxychlor (MXC) causes atresia (follicle death via apoptosis) of antral follicles, but little is known about the mechanisms by which MXC does so. Oxidative stress is(More)
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that binds various environmental contaminants. Despite our knowledge regarding the role of the AhR in mediating toxicity, little is known about the physiological role of the AhR. Previous studies indicate that the AhR may regulate folliculogenesis, because AhR-deficient (AhRKO)(More)