Different environmental chemicals can affect the reproductive capability of a variety of organisms, depending on the timing and dose of exposure, and are thought to impact human reproduction as well. One example is the phytoestrogen, genistein, which when given to neonatal female mice has long-term effects on their ability to reproduce. The underlying causes of their infertility, however, are not known. We are using the neonatal genistein model of infertility to determine how estrogenic compounds affect female reproductive tract development and function, and how these compounds influence embryo development within the female reproductive tract through the time of implantation. These studies are relevant to human fertility because genistein levels similar to those reached in our mouse model are measured in babies on soy-based infant formula. Female mice treated neonatally with the phytoestrogen genistein are infertile because of deficiencies in embryo development in the oviduct and defects in implantation. During the past year we performed a series of experiments to characterize the abnormalities in the oviduct. We found significant alterations in morphology and permanently altered patterns of gene expression of factors known to modulate female reproductive tract development. This work was published in Environmental Health Perspectives. We also found that the abnormal oviduct environment causes abnormalities in blastocyst development that are likely a consequence of alterations in the oviduct mucosal immune response to pregnancy;however, these abnormalities do not preclude successful term development after embryo transfer. These studies will be continued. There is evidence in rodents that prenatal exposure to environmentally relevant doses of bisphenol A (BPA) causes abnormal ovarian and female reproductive tract development. Although the rodent studies have raised concerns regarding human exposure to BPA, there is minimal information regarding the effects of BPA on development in humans or non-human primate models. Dr. Patricia Hunt (Washington State Univ.) and Dr. Cathi VandeVoort (UC Davis Primate Center) initiated a study to examine the effects of maternal BPA exposure during either the 2nd or 3rd trimesters of pregnancy on development of female Rhesus monkey fetuses. The monkeys were treated using 2 different BPA dosing strategies, and all tissues have been collected. We are evaluating the morphology and gene expression in the female reproductive tract. This project will generate a gene expression profile of developing normal Rhesus monkey oviduct and uterus, and also provide evidence regarding whether there are differences in the gene expression profiles and histology when comparing control and BPA-treated groups.

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Li, Yin; Hamilton, Katherine J; Wang, Tianyuan et al. (2018) DNA methylation and transcriptome aberrations mediated by ER? in mouse seminal vesicles following developmental DES exposure. Proc Natl Acad Sci U S A 115:E4189-E4198
Jefferson, Wendy N; Kinyamu, H Karimi; Wang, Tianyuan et al. (2018) Widespread enhancer activation via ER? mediates estrogen response in vivo during uterine development. Nucleic Acids Res 46:5487-5503
Suen, Alisa A; Jefferson, Wendy N; Williams, Carmen J et al. (2018) Differentiation Patterns of Uterine Carcinomas and Precursor Lesions Induced by Neonatal Estrogen Exposure in Mice. Toxicol Pathol 46:574-596
Williams, Carmen J; Chu, Alison; Jefferson, Wendy N et al. (2017) Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis, mimicking features of human placental insufficiency. J Pathol 242:246-259
Ho, Shuk-Mei; Cheong, Ana; Adgent, Margaret A et al. (2017) Environmental factors, epigenetics, and developmental origin of reproductive disorders. Reprod Toxicol 68:85-104
Suen, Alisa A; Jefferson, Wendy N; Wood, Charles E et al. (2016) SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer. Mol Cancer Res 14:849-58
Winuthayanon, Wipawee; Bernhardt, Miranda L; Padilla-Banks, Elizabeth et al. (2015) Oviductal estrogen receptor ? signaling prevents protease-mediated embryo death. Elife 4:e10453
Jensen, E T; Daniels, J L; Stürmer, T et al. (2015) Hormonal contraceptive use before and after conception in relation to preterm birth and small for gestational age: an observational cohort study. BJOG 122:1349-61
Heindel, Jerrold J; Newbold, Retha R; Williams, Carmen J et al. (2015) Lou Guillette--in memorandum. Mol Reprod Dev 82:Fmi-v
Jensen, E T; Daniels, J L; Stürmer, T et al. (2014) Maternal hormonal contraceptive use and offspring overweight or obesity. Int J Obes (Lond) 38:1275-81

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