Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey

Patricia A Hunt; Crystal Lawson; Mary Gieske; Brenda Murdoch; Helen Smith; Alyssa Marre; Terry Hassold; Catherine A VandeVoort

doi:10.1073/pnas.1207854109

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Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey

Journal article

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Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey

Patricia A Hunt, Crystal Lawson, Mary Gieske, Brenda Murdoch, Helen Smith, Alyssa Marre, Terry Hassold and Catherine A VandeVoort

Proceedings of the National Academy of Sciences - PNAS, Vol.109(43), pp.17525-17530

10/23/2012

DOI: https://doi.org/10.1073/pnas.1207854109

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https://hdl.handle.net/2376/105737

PMCID: PMC3491481

PMID: 23012422

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Abstract

Benzhydryl Compounds

Administration, Oral

Ovarian Follicle - embryology

Macaca mulatta

Maternal Exposure

Dose-Response Relationship, Drug

Meiosis - drug effects

Ovarian Follicle - drug effects

Animals

Mitosis - drug effects

Female

Phenols - administration & dosage

Mice

Oogenesis - drug effects

Phenols - pharmacology

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.

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Title: Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey
Creators: Patricia A Hunt - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA. pathunt@vetmed.wsu.edu
Crystal Lawson
Mary Gieske
Brenda Murdoch
Helen Smith
Alyssa Marre
Terry Hassold
Catherine A VandeVoort
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.109(43), pp.17525-17530
Academic Unit: Center for Reproductive Biology; Molecular Biosciences, School of
Publisher: United States
Grant note: R01 ES013527 / NIEHS NIH HHS R01 ES016770 / NIEHS NIH HHS P51 OD011107 / NIH HHS P51 RR000169 / NCRR NIH HHS OD011107 / NIH HHS ES016770 / NIEHS NIH HHS ES013527 / NIEHS NIH HHS HD21341 / NICHD NIH HHS R01 HD021341 / NICHD NIH HHS RR00169 / NCRR NIH HHS R37 HD021341 / NICHD NIH HHS
Identifiers: 99900547071901842
Language: English
Resource Type: Journal article