Phytoestrogen in soy impedes egg, embryo growth, finds mouse study.

Jul 28, 2009

Chan, W-H. 2009. Impact of genistein on maturation of mouse oocytes, fertilization and fetal development. Reproductive Toxicology 28:52-58.




2009-0715 tofu salad
FotoosVanRobin, Flickr.

Women who are having difficulty conceiving may want to cut back on their soy consumption after a mouse study reveals that dietary exposure to genistein, a compound found in soy foods, can reduce the odds of a successful pregnancy in multiple ways. The study examined the impact of genistein exposure on oocytes, or eggs, from adult mice and found it can impair oocyte maturation, reduce their potential to become fertilized and hamper the growth of the newly formed embryo. The results reveal how natural compounds like genistein may have both risks – it can act as an endocrine disruptor to affect female reproduction – and benefits - such as protecting the heart.

 

Context

Oocytes are the female germ cell or “egg.” They reside in a multi-cellular structure called a follicle in the ovary. Humans ovulate one oocyte per month as part of the menstrual cycle. Mice ovulate several oocytes every 4 to 5 days, but the overall structure of the mouse follicle and the human follicle is very similar.

Phytoestrogens are a class of estrogen-like compounds produced by plants, most notably soybeans and other legumes.  They are also found in seeds, nuts, and some vegetables.  Consumption of a diet rich in foods containing phytoestrogens is associated with a lower risk of developing heart diease and obesity.

Genistein is an isoflavone phytoestrogen that is commonly found in soy and soy-based foods including soy milk, tofu, dietary supplements and soy infant formula. Infants reared on soy formula consume approximately 6-9 milligrams per kilograms of isoflavones per day. Adults eating a traditional Asian diet or meeting the FDA recommendation of 25 g of soy per day consume less than half of that.

Genistein is structurally similar to the hormone estrogen and can interact with estrogen receptors. Numerous prior studies have found that it can interfere with estrogen and affect the development of the female reproductive system in laboratory animals.  Thus there is some concern that genistein could act like an endocrine disruptor in some cases.

What did they do?

For one set of experiments, mice were exposed to genistein for 4 days through their drinking water. Their oocytes were then collected and cultured in petri dishes.  For the remaining experiments, the oocyctes were collected from animals that did not eat genistein and then exposed to 1, 5 or 10 micromoles (µM) of genistein in the petri dishes.  In both cases, the oocyte collection and culturing procedure was similar to how in vitro fertilization is done in humans.

Blood levels in people eating soy-rich diets are generally in the range of 1-5 µM, so the exposure levels used in this study are similar to what a human fetus could be exposed to.

What did they find?

In both experiments, genistein affected oocyte maturation, fertilization rates and embryo development.

Exposure to genistein impaired the ability of the oocytes to mature. The effect was dose dependent, meaning that the fewest number of oocytes matured at the highest dose of genistein.

The capacity for exposed oocytes to become fertilized and progress through early embryonic development was also significantly reduced. Again, the effect was dose dependent and fewer embryos developed at the higher the dose of genistein.

The study also found evidence of improper development including cell death, a process referred to as apoptosis, in newly formed embryos. Cell death is not normal in embryos this young. It is unclear how or why genistein exposure results in embryonic cell death.

These combined results add to a growing body of work demonstrating that genistein may reduce fertility.

What does it mean?

The findings indicate that genistein has the potential to harm mature oocytes and newly formed embryos, effects which could reduce the odds of having a successful pregnancy.

This study was conducted with oocytes collected from mice. It remains to be seen if genistein affects human eggs in similar ways.

The results add to a long list of published studies showing that genistein can act like an endocrine disruptor in laboratory animals.  It is important to recognize, however, that some groups may be more sensitive to the endocrine disrupting effects of genistein than others and that, for many people, a soy-rich diet can have many health benefits.  The data from this study suggest that genstein may be detrimental to women who are newly pregnant or attempting to become pregnant.

Prior research has found that genistein can reduce the potential for mice to become pregnant and affect how the ovary grows and develops, so this new study provides further evidence that genistein could be detrimental to the female reproductive system.

It is widely believed that soy foods have many health benefits but it is not well appreciated that genistein and other phytoestrogens in soy foods could have detrimental effects in some cases. The impact of genistein on embryonic development is significant given that rates of soy consumption are increasing, especially among young women and children. Studies in humans are needed to confirm the findings of this mouse study and the hypothesis that women who are pregnant or trying to conceive may be at more risk from the phytoestrogen than others.

For now, though, the findings suggest that women who are having difficulty conceiving may want to cut back on their soy consumption.

Resources

Ovary 101. About.com: Women's Health

Phytoestrogens. e.hormone, Tulane University.

Jefferson, W, R Newbold, E Padilla-Banks and M Pepling. 2006. Neonatal genistein treatment alters ovarian differentiation in the mouse: inhibition of oocyte nest breakdown and increased oocyte survival. Biology of Reproduction 74(1): 161-168.

Jefferson, WN, E Padilla-Banks and RR Newbold. 2005. Adverse effects on female development and reproduction in CD-1 mice following neonatal exposure to the phytoestrogen genistein at environmentally relevant doses. Biology of Reproduction 73(4): 798-806.

Kuhnle, GG, C Dell'Aquila, SM Aspinall, SA Runswick, AA Mulligan and SA Bingham. 2008. Phytoestrogen content of beverages, nuts, seeds, and oils. Journal of Agricultural and Food Chemistry 56: 7311-7315.

 

 

 

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