Prenatal Phthalate Exposure Adversely Affects Male Genital Development;

Pesticides & Fungicides Have Transgenerational Affects on Male Fertility

San Diego, CA - June 3, 2005 - Two studies were released today that have identified transgenerational effects on male genital development and fertility due to mothers’ exposure to common phthalates and pesticides/fungicides in the environment. The studies were presented at The Forum on Endocrine Disrupting Chemicals, developed by The Endocrine Society.

The Study for Future Families Research Team, led by 19 doctors from around the country, presented “Prenatal Phthalate Exposure is Associated with Decreased Anogenital Distance (a marker of fetal androgen action) in Human Infant Males.” This is the first study to examine the anogenital distance (AGD) in relation to intrauterine phthalate exposure in humans. Phthalates have been used in wide variety of products for almost a century and are found in products such as perfume and nail polish.

In the study, 85 human mother-son pairs were evaluated to compare neonatal phthalate exposure, as measured by mother’s urine concentration of four phthalate metabolites and infant male (2 to 30 months) AGD measurements, which were standardized for weight to form an anogenital index (AGI).

Comparing the MBP concentration in the highest to lowest quartile, the odds ratio for a shorter-than-predicted AGI was 10.2 (95% CI2.5-42.2). Adjusted AGI also decreased significantly with increases in a score that reflects joint exposure to four key phthalate metabolites. These shortened AGIs occurred in male infants who were exposed prenatally to phthalate metabolites at concentrations found in one quarter of the female population of the United States.

The study, published in the journal Environmental Health Perspectives, supports the hypothesis that prenatal phthalate exposure can adversely affect the male reproductive tract development in male infants at phthalate levels that are found in the general population in the United States.

In another study, published in the journal Science, on endocrine disrupting chemicals, Dr. Michael K. Skinner, Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, discussed a study entitled: “Epigenetic Transgenerational Effects of Endocrine Disrupting Chemicals on the Male Germ-Line and Consequences on Male Fertility and Other Diseases.”

The study researched how endocrine disruptors can interfere with embryonic testes development. The estrogenic pesticide methoxychlor and anti-androgenic fungicide vinclozolin were used as the disruptors. Previous studies have shown that methoxychlor and vinclozolin both interfere with embryonic testes cord formation, and cause increased spermatogenic cell disintegration in the adult teste.

However, this study also found that exposure to these two disruptors by mothers at the time of male sex determination caused a transgenerational characteristic of sperm creation and sub-fertility in the male offspring. This appears to happen by a mechanism involving altered DNA methylation and permanent re-programming of the male germ-line. A series of genes with altered DNA methylation and imprinting were identified.

“In essence, fetal exposure to an endocrine disruptor results in abnormal germ cell differentiation that subsequently influences adult sperm creating capacity and male fertility,” said Skinner. “This phenotype spans several generations through the male germ-line.”

In addition to effects on male fertility, other disease states were observed associated with premature aging, prostate disease, kidney disease and tumor development. The novel observations of transgenerational epigenetic endocrine disruptor actions on male reproduction and other diseases critically impact the potential hazards of these compounds as environmental toxins.

The ability of an environmental compound to induce an epigenetic disease state spanning several generations has significant implications for the study of disease origins, and for areas such as evolutionary biology.

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Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Md. To learn more about the Society, and the field of endocrinology, visit our web site at www.endo-society.org.