title: Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey.
abstract: Widespread use of the endocrine disrupting chemical bisphenol A (BPA) in consumer products has resulted in nearly continuous human exposure. In rodents, low-dose exposures have been reported to adversely affect two distinct stages of oogenesis in the developing ovary: the events of prophase at the onset of meiosis in the fetal ovary and the formation of follicles in the perinatal ovary. Because these effects could influence the reproductive longevity and success of the exposed individual, we conducted studies in the rhesus monkey to determine whether BPA induces similar disturbances in the developing primate ovary. The routes and levels of human exposure are unclear; hence, two different exposure protocols were used: single daily oral doses and continuous exposure via subdermal implant. Our analyses of second trimester fetuses exposed at the time of meiotic onset suggest that, as in mice, BPA induces subtle disturbances in the prophase events that set the stage for chromosome segregation at the first meiotic division. Our analyses of third-trimester fetuses exposed to single daily oral doses during the time of follicle formation revealed an increase in multioocyte follicles analogous to that reported in rodents. However, two unique phenotypes were evident in continuously exposed animals: persistent unenclosed oocytes in the medullary region and small, nongrowing oocytes in secondary and antral follicles. Because effects on both stages of oogenesis were elicited using doses that yield circulating levels of BPA analogous to those reported in humans, these findings raise concerns for human reproductive health.
authors.affiliation: School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA. pathunt@vetmed.wsu.edu
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Hunt
authors.forename: Crystal
authors.initials: C
authors.lastname: Lawson
authors.forename: Mary
authors.initials: M
authors.lastname: Gieske
authors.forename: Brenda
authors.initials: B
authors.lastname: Murdoch
authors.forename: Helen
authors.initials: H
authors.lastname: Smith
authors.forename: Alyssa
authors.initials: A
authors.lastname: Marre
authors.forename: Terry
authors.initials: T
authors.lastname: Hassold
authors.forename: Catherine A
authors.initials: CA
authors.lastname: VandeVoort
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D018811:Maternal Exposure; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009866:Oogenesis / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects* / Q000196:embryology; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds