Document Detail

Neonatal phytoestrogen exposure alters oviduct mucosal immune response to pregnancy and affects preimplantation embryo development in the mouse.
MedLine Citation:
PMID:  22553218     Owner:  NLM     Status:  MEDLINE    
Treatment of neonatal mice with the phytoestrogen genistein (50 mg/kg/day) results in complete female infertility caused in part by preimplantation embryo loss in the oviduct between Days 2 and 3 of pregnancy. We previously demonstrated that oviducts of genistein-treated mice are "posteriorized" as compared to control mouse oviducts because they express numerous genes normally restricted to posterior regions of the female reproductive tract (FRT), the cervix and vagina. We report here that neonatal genistein treatment resulted in substantial changes in oviduct expression of genes important for the FRT mucosal immune response, including immunoglobulins, antimicrobials, and chemokines. Some of the altered immune response genes were chronically altered beginning at the time of neonatal genistein treatment, indicating that these alterations were a result of the posteriorization phenotype. Other alterations in oviduct gene expression were observed only in early pregnancy, immediately after the FRT was exposed to inflammatory or antigenic stimuli from ovulation and mating. The oviduct changes affected development of the surviving embryos by increasing the rate of cleavage and decreasing the trophectoderm-to-inner cell mass cell ratio at the blastocyst stage. We conclude that both altered immune responses to pregnancy and deficits in oviduct support for preimplantation embryo development in the neonatal genistein model are likely to contribute to infertility phenotype.
Wendy N Jefferson; Elizabeth Padilla-Banks; Jazma Y Phelps; Amy M Cantor; Carmen J Williams
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-07-01
Journal Detail:
Title:  Biology of reproduction     Volume:  87     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-11-30     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10, 1-10     Citation Subset:  IM    
Reproductive Medicine Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
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MeSH Terms
Animals, Newborn
Embryonic Development / drug effects*,  genetics,  immunology,  physiology
Gene Expression Regulation, Developmental / drug effects
Genes, MHC Class II / drug effects
Genistein / administration & dosage,  toxicity*
Immunity, Mucosal / drug effects*,  genetics
Infertility, Female / chemically induced,  genetics,  immunology,  metabolism
Inflammation Mediators / metabolism
Oviducts / drug effects*,  immunology*,  metabolism,  pathology
Phytoestrogens / administration & dosage,  toxicity*
Grant Support
Reg. No./Substance:
0/Inflammation Mediators; 0/Phytoestrogens; 446-72-0/Genistein

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