132infertility. We use this mouse model to define stages of gametogenesis impaired by deficient BRCA2 expression and find evidence for a role in meiosis and gametogenic success in both males and females. Materials and methods Isolation and characterization of BACsHuman genomic BAC library filters obtained from Roswell Park Cancer Institute (now available at BACPAC Resource Center at the Children's Hospital Oakland Research Institute in Oakland, California) were screened using probes derived from PCR amplified DNA fragments from the 5′ (nucleotides 331-850) and 3′ (nucleotides 9852-10420) ends of the human BRCA2 cDNA (NM 000059). Thirteen clones were obtained from the human BAC library and seven were hybridized to both end probes. To identify the clone with the largest upstream and downstream regions, the T7 and SP6 ends of each BAC clone were sequenced and compared with the published sequence of human BRCA2 region. Human BRCA2 BAC, RP11-777I19 was selected to generate transgenic mice. The insert size (~165 kb) was confirmed by pulsed field gel electrophoresis of NotI-digested BAC DNA.

The aryl hydrocarbon receptor (AhR) regulates the toxicity of environmental contaminants such as 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD). As the physiological role of the AhR in the ovary is unknown, the purpose of this study was to test the hypothesis that the AhR regulates the appearance and numbers of ovarian follicles. Ovaries were harvested from AhR-deficient (AhRKO) and wild-type mice on gestational day 18 (GD 18) and postnatal days (PND) 2-3, 8, 32-35, and 53. Complete serial sections of ovaries were evaluated histologically for the presence of germ cells and follicles. On GD 18, there was no difference in the number of germ cells per ovary between AhRKO and wild-type fetuses. However, by PND 2-3, AhRKO mice had significantly more fully formed primordial follicles (AhRKO = 38,440 +/- 3632 versus wild-type = 21,120 +/- 2688) and fewer single germ cells than wild-type mice (AhRKO = 12,696 +/- 1192 vs. wild-type = 18,160 +/- 720). On PND 8 and 32-35, there was no difference in the number of follicles between AhRKO and wild-type mice but by PND 53, AhRKO mice had significantly fewer antral follicles than wild-type (AhRKO = 3416 +/- 480 vs. wild-type = 6776 +/- 1024). Taken together, these results suggest that the AhR may play a role in the formation of primordial follicles and the regulation of antral follicle numbers.

Future studies are needed to confirm previous findings and to identify additional risk factors for hot flashes. Such studies will increase our understanding of the etiology of hot flashes and may lead to better treatments and preventive measures for this condition.

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) mice have fewer preantral and antral follicles than wild-type (WT) mice during postnatal life. Thus, the first objective of the present study was to test the hypothesis that AhR deficiency reduces the numbers of preantral and antral follicles by slowing growth and/or increasing atresia of follicles. Because alterations in follicular growth or atresia can affect the ability to ovulate, the second objective was to test whether AhR deficiency reduces the number of ovulated eggs. To test these hypotheses, follicular growth was compared in WT and AhRKO ovaries using morphometric techniques and by measuring the ability of the ovary and follicles to grow in response to eCG. Atresia was compared in WT and AhRKO ovaries using morphometric techniques, TUNEL assays, and 3'-end labeling of fragmented DNA. Ovulation was compared in WT and AhRKO mice by assessing the number of corpora lutea per ovary. The results indicate that follicular growth and ovulation were reduced in AhRKO ovaries compared to WT ovaries. The WT ovaries had a 1.5-fold increase in the number of preantral and antral follicles between Postnatal Days 32 and 45, were more responsive to eCG, and contained more corpora lutea than AhRKO ovaries. In contrast, no significant difference was observed in the incidence of atresia in WT and AhRKO ovaries. Taken together, these results suggest that the AhR may regulate growth, but not atresia, of preantral and antral follicles in the mouse ovary.