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BOR - Papers in Press, published online ahead of print September 28, 2005.
Biol Reprod 2005, 10.1095/biolreprod.105.045724
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BIOLOGY OF REPRODUCTION 74, 161–168 (2006)
DOI: 10.1095/biolreprod.105.045724
© 2006 by the Society for the Study of Reproduction, Inc.


Research Article

Neonatal Genistein Treatment Alters Ovarian Differentiation in the Mouse: Inhibition of Oocyte Nest Breakdown and Increased Oocyte Survival1

Wendy Jefferson 2 34 , Retha Newbold 3, Elizabeth Padilla-Banks 3, and Melissa Pepling 5

Developmental Endocrinology and Endocrine Disruptor Section,3 Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, NIH/DHHS, Research Triangle Park, North Carolina 27709 Department of Environmental and Molecular Toxicology,4 North Carolina State University, Raleigh, North Carolina 27605 Department of Biology,5 Syracuse University, Syracuse, New York 13210

ABSTRACT

Early in ovarian differentiation, female mouse germ cells develop in clusters called oocyte nests or germline cysts. After birth, mouse germ cell nests break down into individual oocytes that are surrounded by somatic pregranulosa cells to form primordial follicles. Previously, we have shown that mice treated neonatally with genistein, the primary soy phytoestrogen, have multi-oocyte follicles (MOFs), an effect apparently mediated by estrogen receptor 2 (ESR2, more commonly known as ERbeta). To determine if genistein treatment leads to MOFs by inhibiting breakdown of oocyte nests, mice were treated neonatally with genistein (50 mg/kg per day) on Days 1–5, and the differentiation of the ovary was compared with untreated controls. Mice treated with genistein had fewer single oocytes and a higher percentage of oocytes not enclosed in follicles. Oocytes from genistein-treated mice exhibited intercellular bridges at 4 days of age, long after disappearing in controls by 2 days of age. There was also an increase in the number of oocytes that survived during the nest breakdown period and fewer oocytes undergoing apoptosis on Neonatal Day 3 in genistein-treated mice as determined by poly (ADP-ribose) polymerase (PARP1) and deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL). These data taken together suggest that genistein exposure during development alters ovarian differentiation by inhibiting oocyte nest breakdown and attenuating oocyte cell death.

developmental biology, environment, mechanisms of hormone action, ovary


FOOTNOTES

1 This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

2 Correspondence: Wendy Jefferson, NIEHS, 111 Alexander Dr., Research Triangle Park, NC 27709. FAX: 919 541 4634; jeffers1{at}niehs.nih.gov




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