The disinfection of drinking water was an important public health achievement of the 20th century because it significantly reduced the numbers of deaths and illnesses from drinking contaminated water. The disinfection process, however, leads to the production of water disinfection by-products (DBPs), which have been linked to toxicity in numerous systems. A major chemical class of DBPs includes the haloacetic acids (HAAs) such as iodoacetic acid (IAA), bromoacetic acid (BAA), and chloroacetic acid (CAA). Although previous studies indicate that some HAA exposures are associated with increased cancer risk, virtually nothing is known about the effects of adult exposure to IAA, BAA, and CAA on the ovary and female fertility. It is important to determine whether adult exposure to HAAs causes ovarian toxicity because women are exposed to HAAs daily, and ovarian toxicity often leads to female subfertility or infertility. Thus, we examined the effects of IAA, BAA, and CAA on the main functional unit of the ovary, the antral follicle. Our preliminary data indicate that environmentally relevant levels of IAA, BAA, and CAA significantly inhibit growth of antral ovarian follicles and the ability of antral follicles to produce the sex steroid hormone estradiol (E2). Slow follicle growth and low E2 levels are of concern because they are linked to increased atresia (death of follicles) and subfertility/infertility. Although preliminary data suggest that the selected HAAs may reduce fertility, they do not directly determine whether this is the case because they were obtained from in vitro studies. Thus, the goal of the proposed studies is to test the hypothesis that IAA, BAA, and CAA lead to gene/protein changes in the ovary to cause female subfertility/infertility. To test his hypothesis, these studies will: 1) determine whether and how HAAs (IAA, BAA, and CAA) inhibit ovarian follicle growth and cause female subfertility/infertility and 2) identify the molecular factors that are altered by HAAs (IAA, BAA, and CAA) and determine their relationship to altered follicle growth and female subfertility/infertility. This will be the first work to examine the effects of adult exposure to HAAs on the ovary and female fertility. As such, it will open a new area of research, which is critical for helping determine whether the selected HAAs are female reproductive health hazards and should be considered for regulation of use in adult women.

The results of this study will provide a better understanding of the effects of selected disinfection by- products on female reproduction. This ultimately may lead to the development of preventive strategies and/or new treatments for disinfection by-product-induced toxicity in women.