title: Developmental programming: differential effects of prenatal exposure to bisphenol-A or methoxychlor on reproductive function.
abstract: Increased occurrence of reproductive disorders has raised concerns regarding the impact of endocrine-disrupting chemicals on reproductive health, especially when such exposure occurs during fetal life. Prenatal testosterone (T) treatment leads to growth retardation, postnatal hypergonadotropism, compromised estradiol-positive feedback, polycystic ovaries, and infertility in the adult. Prenatal dihydrotestosterone treatment failed to affect ovarian morphology or estradiol-positive feedback, suggesting that effects of prenatal T may be facilitated via conversion of T to estradiol, thus raising concerns regarding fetal exposure to estrogenic endocrine-disrupting chemicals. This study tested whether fetal exposure to methoxychlor (MXC) or bisphenol A (BPA) would disrupt cyclicity in the ewe. Suffolk ewes were administered MXC (n=10), BPA (n=10) (5 mg/kg.d sc in cotton seed oil) or the vehicle (C; n=16) from d 30 to 90 of gestation. On d 60 of treatment, maternal MXC concentrations in fat tissue and BPA in blood averaged approximately 200 microg/g fat and 37.4+/-3.3 ng/ml, respectively. Birth weights of BPA offspring were lower (P<0.05) relative to C. There was no difference in the time of puberty between groups. BPA females were hypergonadotropic during early postnatal life and ended their breeding season later, compared with C. Characterization of cyclic changes after synchronization with prostaglandin F2alpha in five C, six MXC, and six BPA females found that the onset of the LH surge was delayed in MXC (P<0.05) and the LH surge magnitude severely dampened (P<0.05) in BPA sheep. These findings suggest that prenatal BPA and MXC exposure have long-term differential effects on a variety of reproductive endocrine parameters that could impact fertility.
authors.affiliation: Department of Pediatrics, 300 North Ingalls Building, Room 1109 SW, Ann Arbor, University of Michigan 48109-0404, USA.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Savabieasfahani
authors.forename: Kurunthachalam
authors.initials: K
authors.lastname: Kannan
authors.forename: Olga
authors.initials: O
authors.lastname: Astapova
authors.forename: Neil P
authors.initials: NP
authors.lastname: Evans
authors.forename: Vasantha
authors.initials: V
authors.lastname: Padmanabhan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D001724:Birth Weight; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005865:Gestational Age; D048788:Growth and Development / Q000187:drug effects; D008297:Male; D008731:Methoxychlor / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012098:Reproduction / Q000187:drug effects*; D012741:Sexual Maturation / Q000187:drug effects; D012756:Sheep; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D008731:Methoxychlor; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds