Our environment is widely contaminated with chemicals that act biologically as estrogen mimics (xenoestrogens). Among these are pesticides, industrial chemicals, plasticizers, and various phytoestrogens are increasingly consumed in the diet. Evidence exists that reproduction has been deleteriously affected in wildlife and domestic animals that have been exposed to xenoestrogens or that have consumed a diet high in phytoestrogens. Recent enigmatic and alarming observations suggest a decline in human sperm production and quality over the last few decades. While it is presumed that this is due to prenatal/perinatal exposure to xenoestrogens, no definitive evidence supports this assumption. Yet, it is known that a single exposure to extremely high doses of natural or synthetic estrogen can permanently disrupt reproductive function in the male rodent. However, this protocol does not profile the hormone exposure that an organism is likely to encounter due to environmental presence. Thus, the specific objective of this proposal is to examine the effect(s) of chronic, very low dose estrogen exposure upon reproductive system development in the male rat. Is there a differential degree of impairment due to prolonged exposure to different doses of hormone or is there a critical threshold dose at which defects become evident? Are potential defects due to estrogen agonist action or an androgen antagonism? Do potential developmental anomalies represent permanent, irreversible consequences or typify an interrupted, delayed maturational progression? Continuous release estrogen pellets will be subcutaneously implanted into rats at birth. Positive controls will be implanted with antiandrogen pellets; negative controls, with placebo pellets. The biological effects of such hormone exposure will be determined by assessing functional parameters of the Sertoli cell that may be developmentally important in endocrine signaling during prepubertal testis maturation. Additionally, morphometric and histologic analysis of the testis will be carried out during the prepubertal period and into early adulthood. This research will characterize and evaluate more definitively the potential for xenoestrogen disruption of male reproductive function and provide new insight about the biologic effects of environmentally relevant doses of estrogen during the critical period of testicular maturations.
