title: Developmental programming: prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep.
abstract: Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5mg/kgBW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess preovulatory hormonal changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean number or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2-3mm, 4-5mm, and ≥6mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Veiga-Lopez
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Beckett
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: B
authors.initials: B
authors.lastname: Abi Salloum
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA; The Reproductive Sciences Program, University of Michigan, Ann Arbor, MI, USA. Electronic address: vasantha@umich.edu.
authors.forename: V
authors.initials: V
authors.lastname: Padmanabhan
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D052244:Endocrine Disruptors / Q000633:toxicity*; D030762:Estrous Cycle / Q000097:blood / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects; D005865:Gestational Age; D007247:Infertility, Female / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D007986:Luteinizing Hormone / Q000097:blood*; D018811:Maternal Exposure; D006080:Ovarian Follicle / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D012756:Sheep; D013997:Time Factors; D014463:Ultrasonography; D015854:Up-Regulation; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D052244:Endocrine Disruptors; D007986:Luteinizing Hormone; D010636:Phenols; D011374:Progesterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Follicular dynamics; Infertility