Environmentally relevant phthalate exposures and ovarian function

The long-term goal of this research is to facilitate risk assessment, the discovery of infertility- and phthalate-related toxicity biomarkers, and the development of treatments and prevention strategies for infertility in women by identifying and characterizing the cellular and molecular mechanisms by which environmentally relevant exposure to phthalates interact with the ovary. Studies in animal models suggest that phthalates might impair fertility through their ability to disrupt ovarian function. Ovarian follicles, the functional units of the ovary, exist in various stages of development ranging from the most immature primordial follicles to the large pre-ovulary follicles capable of sustaining ovarian steroidogenesis and ovulation. Survival and successful transition from the pre-antral to the large pre-ovulatory follicle stage are required for ovulation and depend on the positive actions of various factors including follicle-stimulating hormone (FSH), insulin-like growth factor 1 (IGF1), and 17β-estradiol (E2). In animal models, the absence of FSH, IGF1, and E2 reportedly results in a common phenotype that includes infertility due to arrest of ovarian follicles in the early antral stage, disrupted granulosa cell function, impaired aromatase expression, and increased follicular death. Therefore, the FSH-IGF1-E2 system is critical to ovarian function and any chemical exposure that alters this system has the potential to cause infertility. At relatively high doses, phthalates interfere with the FSH and E2 aspects of this system.