Newswise -- A substance found in soy-based infant formula and over-the-counter dietary supplements affects the development of ovaries and eggs in female infant mice, according to a study conducted by researchers at the National Institutes of Health (NIH) and Syracuse University. The study, "Neonatal Genistein Treatment Alters Ovarian Differentiation in the Mouse: Inhibition of Oocyte Nest Breakdown and Increased Oocyte Survival," was published in a recent issue of the journal Biology of Reproduction. Melissa Pepling, assistant professor of biology in The College of Arts and Sciences at Syracuse University, was an investigator on the study.

Genistein, a phytoestrogen, is the primary naturally occurring estrogen in plants, which can mimic the effects of estrogen in the body. Previous research showed that female mice given genistein immediately after birth had irregular menstrual cycles, problems with ovulation, and problems with fertility in their adulthood. Researchers undertook this study to determine when this damage occurs.

Newborn female mice were given different doses of genistein during their first five days of life. The genistein was comparable to what human infants might receive in a soy-based formula (6-9 mg/kg per day). All of the mice that were treated were affected by genistein in some way. The mice that received low levels of genistein were subfertile, meaning they had fewer pups in each litter and fewer pregnancies. The mice that received the high dose were infertile, and the mice with the highest dose were infertile and had a high percentage of eggs that remained in clusters and did not develop normally. In order for an egg to be able to be fertilized, it must break down from clusters into individual eggs (oocytes). The researchers believe that genistein inhibits this process.

The largest difference between the treated and untreated mice occurred at six days of age, when untreated mice had 57 percent single or unclustered egg cells, compared to only 36 percent found in genistein-treated mice.

"It is not yet clear how genistein works and how it causes these effects," says Pepling. "This will be the focus of future studies." Although human testing has not yet been conducted, Pepling points out that pregnant or nursing mothers should be cautious when considering using soy-based products. Experiments on pregnant mice do not show effects of genistein on the ovary, but do show other developmental abnormalities.

Pepling has been working on mouse oogenesis (how eggs develop) since 1995. She became involved in the study about three and a half years ago, when she met the study's lead researcher, Wendy Jefferson of the National Institute of Environmental Health Sciences.

During the study, Jefferson injected the mice with genistein and harvested the ovaries. Pepling labeled the ovaries with markers for the oocytes, examined them using microscopy, and performed the quantitative analysis.

The research yielded mixed results, suggesting some beneficial effects as well adverse effects of genistein, depending on the timing of exposure, dose level and endpoint examined. Some studies show that exposure to genistein early in life prevents carcinogen-induced mammary gland cancer, while others show increased mammary gland cancer occurs following treatment during specific developmental windows. Others have shown improved cholesterol synthesis rates of human infants consuming soy-based formulas.

However, vegetarian diets usually contain high levels of soy, and recent epidemiology reports have shown an association of a vegetarian diet during pregnancy with an increased incidence of hypospadias (a urological birth defect) in male offspring and an increase in autoimmune disease and the use of allergy medicines in children fed soy-based infant formulas.