Soy protein renders womb unsuitable for pregnancy.

Jan 26, 2009

Jefferson WN, E Padilla-Banks, EH Goulding, SC Lao, RR Newbold and CJ Williams. 2008. Neonatal exposure to genistein disrupts ability of female mouse reproductive tract to support preimplantation embryo development and implantation. Biology of Reproduction doi:10.1095/biolreprod.108.073171.




J.P. Myers
Soy milk
A soy protein, genistein,  long known to affect fertility can change how pregnancies start and progress in female mice treated with it as newborns. The changes make it harder for fertilized eggs to implant and grow, possibly contributing to infertility. The effects were observed at levels comparable to those experienced by human infants feeding on soy formula.

Context

Phytoestrogens are found in a wide range of plants. The compounds can act like the natural female hormone estrogen in people. They produce mixed effects on the development and function of the reproductive system.

Naturally-occurring sources of phytoestrogens in the diet include soy-based food products and soy supplements, including infant formula and soy milk. Soybeans contain two major phyoestrogens: genistein and daidzein.

Previous studies suggest that soy products can affect female reproduction. For example, the vagina of baby girls fed soy formula was found to develop more tissues and was thicker than in girls fed formulas of either breast milk or cow milk. Also, women had significantly longer menstrual cycles if they were fed soy-based formulas as infants compared to girls raised on cow milk-based formulas.

These findings are consistent with the results of laboratory studies. For example, the reproductive cycle of rats and mice was altered altered by exposure to genistein early in life; treated animals also had a higher incidence of infertility and cancer of the reproductive tract as they aged.

In mammals, pregnancy occurs after a fertilized egg moves into the uterus and become intertwined with the organ's lining. This process, which is known as implantation, connects the embryo to the mother and allows for transfer of food and other materials to support development of the embryo.

A successful pregnancy depends on this important step. If implantation fails the pregnancy will be lost.

It is increasing clear from a wide range of scientific studies that exposure to contaminants before birth and in early life can lead to disease in adulthood. Body systems are believed to be reprogrammed during early development.  These changes may lead to obesity, diabetes, cancer and other illnesses later in life, as explained by the "fetal origins of disease" hypothesis.

What did they do?

Researchers from the US National Institute of Environmental Health Sciences wanted to find out why and how genistein causes infertility in rodents. To do this, they conducted a multi-part experiment.

To begin, female mice pups were injected on days 1 through 5 after birth with either corn oil for controls or genistein at 50 milligrams/kilogram of body weight. Mice fed this amount have circulating levels in the blood that are similar to those found in infants fed soy formula.

The researchers then retrieved either unfertilized eggs or fertilized embryos from the female mice to assess egg health and reproductive organ development .

They set up a series of experiments to ask several questions:

First, could unfertilized eggs grow to early development?

Second, could naturally fertilized embryos grow properly in a normal, untreated mouse?

Third, could fertilized embryos taken from untreated mice grow normally in the treated female mice?

What did they find?

Genistein impaired the implantation process in the female mice that were treated as newborns and mated after sexual maturity. After mating, the number of embryos retrieved from genistein-treated mice was about half the number of those collected from control mice.

Fewer implantation sites were present in the uterus of genistein-treated mice compared to control.

Together, these findings suggest that the reproductive tract environment in the genistein-treated mice is likely not optimal for embryonic development.

Tested in vitro, treated and control eggs were equally capable of being fertilized. However, embryos from genistein-treated females developed more slowly than controls. Over time this difference disappeared.

What does it mean?

Genistein affects the uterus and the reproductive tract -- not the egg quality -- of the adult female mice that were treated with the soy phytoestrogen while in the womb. Fertilized embryos developing in the treated females did not attach and thrive as well as embryos in the control animals, even though eggs from genistein-treated females were as healthy as those from their unexposed counterparts.

The genistein-treated mice also lost more embryos early in their development. Embryo death means fewer births and higher rates of infertility.

Together, the results suggest that the uterus may be an important factor in genistein-induced infertility.

These findings pinpoint one actual cause of the observed infertility of early life exposure to genistein. They also highlight the need for a much better understanding of how soy infant formulas and other products fed to newborns and infants may influence a developing baby's reproductive life.

Egg quality was not affected by newborn genistein treatment. The immature eggs from genistein-treated mice developed normally and produced fertile female mice just like in the controls. 

These findings add to a growing body of evidence that implies that newborns that eat soy-based products may be predisposed to lower reproductive success as adults.

Resources

Akingbemi BT, TD Braden, BW Kemppainen, KD Hancock, JD Sherrill, SJ Cook, X He and JG Supko. 2007. Exposure to phytoestrogens in the perinatal period affects androgen secretion by testicular Leydig cells in the adult rat. Endocrinology 148(9):4475-4488.

Bernbaum JC, DM Umbach, NB Ragan, JL Ballard, JI Archer, H Schmidt-Davis and WJ Rogan. 2008. Pilot studies of estrogen-related physical findings in infants. Environmental Health Perspectives 116(3):416-20.

Curtis HS,  EH Goulding, EM Eddy and KS Korach. 2002. Studies using the estrogen receptor alpha knockout uterus demonstrate that implantation but not decidualization-associated signaling is estrogen dependent. Biology of Reproduction 67(4):1268-1277.

Database on the isoflavone content of foods. US Department of Agriculture and Iowa State University.

Hoey L, IR Rowland, AS Lloyd, DB Clarke and H Wiseman. 2004. Influence of soya-based infant formula consumption on isoflavone and gut microflora metabolite concentrations in urine and on faecal microflora composition and metabolic activity in infants and children. British Journal of Nutrition 91(4):607-616.

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.

Kouki T, M Kishitake, M Okamoto, I Oosuka, M Takebe and K Yamanouchi. 2003. Effects of neonatal treatment with phytoestrogens, genistein and daidzein, on sex difference in female rat brain function: estrous cycle and lordosis. Hormone and Behavior 44(2):140-5.

Lewis RW, N Brooks, GM Milburn, A Soames, S Stone, M Hall and J Ashby. 2003. The effects of the phytoestrogen genistein on the postnatal development of the rat. Toxicological Sciences 71(1):74-83.

Newbold RR, EP Banks, B Bullock and WN Jefferson. 2001. Uterine adenocarcinoma in mice treated neonatally with genistein. Cancer Research; 61(11):4325-8.

Rozman KK, J Bhatia, AM Calafat, C Chambers, M Culty, RA Etzel, JA Flaws, DK Hansen, PB Hoyer, EH Jeffery, JS Kesner, S Marty, JA Thomas and D Umbach. 2006. NTP-CERHR expert panel report on the reproductive and developmental toxicity of genistein. Birth Defects Research Part B: Developmental and Reproductive Toxicology 77(6):485-638.

Setchell KD, L Zimmer-Nechemias, J Cai and JE Heubi. Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet 1997; 350:23-27.

Strom BL, R Schinnar, EE Ziegler, KT Barnhart, MD Sammel, GA Macones, VA Stallings, JM  Drulis, SE Nelson and SA Hanson. 2001. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. Journal of American Medical Association 286(7):807-14.

 

 

 

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