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Environmental Factor, June 2012

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Genistein exposure linked to abnormal immune response and infertility

By Robin Arnette

Wendy Jefferson, Ph.D.

Wendy Jefferson (Photo courtesy of Steve McCaw)

Carmen Williams, M.D., Ph.D.

Carmen Williams (Photo courtesy of Steve McCaw)

Previous research by NIEHS scientists determined that female mouse pups exposed to the plant estrogen genistein a short time after birth grew up to be barren. In their latest work, the NIEHS team suggests that changes to the immune system are partly responsible for this genistein-induced rodent infertility.

Laboratory of Reproductive and Developmental Toxicology biologist Wendy Jefferson, Ph.D., and her colleagues working in the Reproductive Medicine Group headed by Carmen Williams, M.D., Ph.D., published their findings online in the May 2 issue of the journal Biology of Reproduction.

Physiologic doses altered gene expression in mice

Jefferson treated female pups on postnatal days 1-5 with either corn oil as a control or 50 milligrams per kilogram per day of genistein, which exposes the mouse pups to the same amount of genistein present in the bloodstream of human babies following ingestion of soy-based infant formulas. She then examined the mice as adults, looking at gene expression in the oviducts, also known as the Fallopian tubes, which transport embryos to the uterus or womb. She found that a large number of immune response genes were different in the genistein-exposed mice. Jefferson said her group also observed that half of their embryos died in the oviduct, and the ones that survived didn’t develop like the controls.

“We can’t for sure say the immune response changes caused the embryos to develop abnormally,” Jefferson maintained, “although we think it’s pretty likely.”

Williams explained that if genistein caused the oviduct to become inflamed, it made sense that infertility would be the likely result.

“We know that in humans, inflammation of the oviducts greatly decreases the chance of a woman becoming pregnant because fluid from the inflamed tubes hurts the embryos,” she said.

Intake of relatively low levels of plant estrogens occur through the diet, but much higher amounts can be ingested through nutritional supplements or soy-based infant formulas. Because the human reproductive tract develops over a long period of time, beginning in the womb and continuing into adolescence, the study’s results suggest that exposure to high plant estrogen levels during these times of development could affect fertility in women.

Citation: Jefferson WN, Padilla-Banks E, Phelps JY, Cantor AM, Williams CJ. 2012. Neonatal phytoestrogen exposure alters oviduct mucosal immune response to pregnancy and affects preimplantation embryo development in the mouse. Biol Reprod; doi:10.1095/biolreprod.112.099846 [Online 2 May 2012].

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