Grant: Operating Grant

Humans are exposed to chemicals from the environment and their diet throughout life, starting at conception. Many environmental chemicals are called endocrine disruptors because they mimic or disrupt natural hormones, including estrogens and androgens. Fetal exposure to environmental chemicals has been correlated with negative effects on male reproduction in human and animals, and it is believed to play a role in the rise of infertility and testicular cancers in humans. However, most studies carried out on animals use high levels of single compounds, rather than the mixtures of chemicals in low doses to which humans are usually exposed. To determine the real impact of environmental chemicals, we propose to examine the reproductive effects of combinations of compounds using low doses reflecting human exposures. One particular area of concern is the exposure of the unborn babies to chemicals through their mothers. Thus, we will study the consequences of exposing pregnant rats to chemicals, alone or in combination, using low doses corresponding to levels encountered by mothers and their babies. We will use a plant estrogen abundant in food and a ubiquitous plasticizer which has anti-androgenic properties. Both chemicals have been found in the amniotic fluid of pregnant women, confirming that they reach the fetus. In preliminary studies, we found that adult rats that were exposed as fetuses to such mixtures developed testicular fibrosis, an abnormal accumulation of fibrous tissue in the testis, later in life. Because fibrosis is linked to infertility in men, we propose to determine the origins of these changes, and to examine whether the mixture is worst than each compound alone for the reproductive system of the rats. We will investigate if treating rats with an anti-fibrosis drug can prevent these negative effects. These studies should help predict the risks created by chemical mixtures in the environment to the reproductive system of men.