Relevance of “SCOTS' PARADOX” for reproductive biology?

embryo transfer, women were sedentary a median of 9.9 waking hours/day (IQR: 8.9-11.1) and participated in moderate/vigorous activity for a median of 15.3 minutes/day (IQR: 7.3-24.4). Time spent sedentary or in moderate/vigorous activity following embryo transfer did not differ by IVF outcome. CONCLUSION: Physical activity following embryo transfer does not appear to differ between those that will or will not conceive; however, women, who are more active in the year preceding IVF are significantly more likely to conceive. Supported by: NIH UL1RR025747. O-103 Monday, October 22, 2012 04:45 PM DEVELOPMENTAL VITAMIN D3 DEFICIENCY DIFFERENTIALLY AFFECTS OVARIAN GENE EXPRESSION PATTERNS IN ADULT FEMALE MICE. J. B. Davis,a Z. Merhi,d B. Tolga-Suntay,b G. Neal-Perry.c aOB/GYN, Montefiore Medical Center, Bronx, NY; bOB/ GYN, Bronx Lebanon Hospital, Bronx, NY; cOB/GYN, Albert Einstein College of Medicine, Bronx, NY; dOB/GYN, University of Vermont College of Medicine, Burlington, VT. OBJECTIVE: To test the hypothesis that early life (in utero + pre-weaning) and peripubertal (early adulthood) diet induced vitamin D3 (VD3) deficiency differentially disrupt AMH, AMH receptor (AMH-R), aromatase (AROM), and vitamin D3 receptor (VDR) gene expression in the ovary. DESIGN: VD3 and its receptor VDR are hypothesized to have key roles in ovarian physiology. It is hypothesized that VDR signaling may regulate AMH and AROM expression. This study uses RT PCR to assess the effect in early vs. peripubertal VD3 deficiency on mouse estrous cyclicity and ovarian gene expression of AROM, AMH, AMH-R and VDR. MATERIALS AND METHODS: Experiments used female mice born to dams fed a VD3 sufficient (VD3+) or deficient diet (VD3-) during early life. Females exposed to early VD3- were weaned onto VD3+ diets throughout puberty and adulthood. Females exposed to early VD3+ were either weaned onto VD3+ (control) or weaned onto a VD3- diet during the peripuberty. All mice were monitored for estrous cyclicity, killed between 8-10 wks of age, ovaries collected, and RNA extracted for RT-PCR (n¼2-9). RESULTS: Females exposed to early or peripubertal VD3- have extended estrous cycles, oligovulation, and early stage follicular arrest. VD3 dietary supplementation post puberty restored estrous cyclicity in adult females exposed to peripubertal but not early VD3-. Compared to controls early VD3results in a 13% increase in AROM, 40% and 38% decrease in VDR and AMH, respectively, and no change in AMH-R expression. Peripubertal VD3 deficiency results in a 23%,109%, and 210% increase in AMH, AMH-R, and VDR, respectively, and a 70% decrease in AROM expression. CONCLUSION: These preliminary data suggest that the developmental stage in which VD3- occurs has an adverse but differential effect of VD3on female reproductive physiology and ovarian gene expression. VD3- restricted to early life appears to impose adverse reproductive axis changes not readily overcome by dietary VD3 supplementation. Supported by: HD066355 and the New England Fertility Society. O-104 Monday, October 22, 2012 05:00 PM DEVELOPMENTAL DIOXIN EXPOSURE PROMOTES A HYPER-INFLAMMATORY PERITONEAL MICROENVIRONMENT WHICH MAY CONTRIBUTE TO THE ENDOMETRIOSIS-LIKE PHENOTYPE. D. R. Glore,a K. L. Bruner-Tran,a K. L. Boyd,b J. A. Lucas,a K. G. Osteen.a aWomen’s Reproductive Health Research Center, Vanderbilt University Medical Center, Nashville, TN; bPathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN. OBJECTIVE: Dioxin is an environmental toxicant that has been associated with reproductive disorders, including infertility and endometriosis. Since mammals are most sensitive to toxicants during development, we established a murine model of in utero dioxin exposure and examined the adult female (F1) offspring. In previous studies F1 females exhibited an endometriosis-like uterine phenotype (reduced progesterone response, heightened inflammatory response and subfertility). Herein, we examined the impact of early life dioxin exposure on the response of the adult peritoneum to an inflammatory challenge and evaluated the impact of peritoneal inflammation on the uterus. DESIGN: Laboratory based study. MATERIALS AND METHODS: C57bl/6 mice were given a single oral dose of dioxin (10ug/kg) on embryonic day 15.5 and allowed to spontaneously deliver. Young adult females (F1; N¼12 and controls N¼12) were challenged with lipopolysaccharide by IP injection (LPS; 200ug/kg). Perito-

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neum, omentum and uteri were collected 0 and 6 hrs after LPS and tissues fixed/frozen for immunohistochemistry and qRT-PCR. RESULTS: Peritoneal wall expression of toll-like receptor-4 (TLR-4) and chemokine ligand 1 (CXCL1) was markedly increased in dioxin-exposed females compared to controls following an LPS challenge. The omentum also exhibited an increased immune cell infiltrate in F1 females, even in the absence of an inflammatory challenge. Immunohistochemical analysis revealed an increase in macrophages within the omentum of F1 mice compared to controls. Enhanced peritoneal inflammation in F1 mice correlated with increased uterine expression of both TLR-4 and nuclear factor kappa. CONCLUSION: Our studies demonstrate that developmental dioxin exposure leads to a heightened peritoneal inflammatory response, which subsequently affects inflammatory markers within the uterus. These studies further suggest that altered peritoneal-uterine communication may contribute to reproductive disorders. Supported by: NIH HD055648, ES014942, AT006245 and The Endometriosis Association. O-105 Monday, October 22, 2012 05:15 PM RELEVANCE OF ‘‘SCOTS’ PARADOX’’ FOR REPRODUCTIVE BIOLOGY? L. Pal,a N. Kidwai,b W. Grant.c aObstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT; bUniversity of Connecticut, Storrs, CT; cSunlight, Nutrition, and Health Research Center (SUNARC), San Francisco, CA. OBJECTIVE: Per Scott’s paradox, exposure to sunshine impacts on a population’s propensity for disease. Population studies suggest that reproductive competence may benefit of sunshine exposure. In humans, solar UVB is a major source of endogenous vitamin D. Vitamin D deficiency related procreative compromise is described in animals; its relevance in humans is unclear. UVB exposure across North America (NA) varies by season and by location. Given that increasing UVB intensity is apparent moving from NorthEast (NE) towards SouthWest (SW) in NA, we studied if the geographical location of IVF centers impacts on success of donor egg IVF (DE-IVF) embryo transfer (ET) cycles. DESIGN: Cross-sectional analyses of SART 2007 data on fresh (FRET) & frozen (FET) DE-IVF cycles. MATERIALS AND METHODS: Annual # cycles,% live birth (LB) following FRET & FET, average # ET, & IVF center’s zip code (lesser numbers reflecting locations in NE with progressively increasing numbers towards SW) was collected from published DE IVF SART 2007 (444 IVF centers). Global coordinates for the reporting IVF center (latitude, longitude & altitude) were obtained (www.wunderground.com). Relationships between LB following DE-FRET & DE-FET with IVF site location & coordinates were assessed. Multivariable regression analyses adjusted for # ET & annual # cycles. Sensitivity analyses restricted analyses to centers undertaking >25 DE & >100 IVF cycles. RESULTS: In SART 2007 data, LB rate following DE FRET and FET cycles was observed to vary by the geographical location of participating clinics in NA. Adjusting for #ET, live birth rates following DE-ET were significantly higher for FRET and FET cycles undertaken in IVF centers located in the SW (region of highest annual UVB exposure) compared to the NE (region of lowest UVB exposure), P<0.05. CONCLUSION: Ecological influences may impact on reproductive success following DE-IVF. Future studies are needed to better elucidate the mechanisms that could explain the observed associations.

O-106 Monday, October 22, 2012 05:30 PM IN THE FETAL RHESUS MONKEY UTERUS, IN UTERO EXPOSURE TO WHOM IT MAY CONCERN: BISPHENOL A (BPA) IS ASSOCIATED WITH CHANGES IN GENE EXPRESSION AND ACCELERATED ADENOGENESIS. K. Calhoun,a E. Padilla-Banks,b C. VandeVoort,d P. Hunt,c C. J. Williams.b aOb/Gyn, Division of Reproductive Endocrinology, UNC Chapel Hill, Chapel Hill, NC; bReproductive Medicine Group, National Institute for Environmental Health Sciences, Research Triangle Park, NC; cMolecular BioSciences, Washington State University, Pullman, WA; dOb/Gyn, UC Davis, Davis, CA. OBJECTIVE: To determine whether daily exposure to BPA during late gestation causes histologic or gene expression changes in the fetal non-human primate (NHP) uterus. DESIGN: Controlled exposure trial in NHP.

Vol. 98, No. 3, Supplement, September 2012