Neonatal phytoestrogen exposure alters oviduct mucosal immune response to pregnancy and affects preimplantation embryo development in the mouse

Biol Reprod. 2012 Jul 1;87(1):10, 1-10. doi: 10.1095/biolreprod.112.099846. Print 2012 Jul.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Embryonic Development / drug effects*
  • Embryonic Development / genetics
  • Embryonic Development / immunology
  • Embryonic Development / physiology
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Genes, MHC Class II / drug effects
  • Genistein / administration & dosage
  • Genistein / toxicity*
  • Immunity, Mucosal / drug effects*
  • Immunity, Mucosal / genetics
  • Infertility, Female / chemically induced
  • Infertility, Female / genetics
  • Infertility, Female / immunology
  • Infertility, Female / metabolism
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Oviducts / drug effects*
  • Oviducts / immunology*
  • Oviducts / metabolism
  • Oviducts / pathology
  • Phytoestrogens / administration & dosage
  • Phytoestrogens / toxicity*
  • Pregnancy


  • Inflammation Mediators
  • Phytoestrogens
  • Genistein