PROJECT SUMMARYApproximately 7.5 million American women are unable to become pregnant or carry a baby to term (impairedfecundity). The ovary is considered a critical target organ in infertility cases based on the large number ofwomen seeking infertility treatment who are unable to release a viable egg from their ovaries. Folliculogenesisis the process through which ovarian follicles the functional units of the ovary develop into a form capable ofsustaining hormone production and ovulating a healthy egg for fertilization. Any environmental exposure thatcauses damage to the ovarian follicle has the potential to impair fecundity in women. Most of what is knownabout toxicity to ovarian follicles has been uncovered in laboratory rodents but there is little available data ontoxicant exposure and related mechanistic toxicology studies in the nonhuman primate the closest laboratoryanimal model to humans. There is therefore a critical need to develop alternative approaches and tools thatsynergize the accessibility and versatility of laboratory rodents with the physiological relevance of thenonhuman primate to deliver high quality ovarian follicle toxicity data. To meet this need this proposal willsupport the formation of a virtual research consortium with expertise in mouse and nonhuman primate ovarianbiology toxicology and computational modeling. The proposed consortium will generate lab-based data on thephysiological and toxicant-induced behavior of ovarian follicles in both species using phthalate as a modeltoxicant to create computational models capable of effectively predicting ovarian follicle responses to chemicalinsults in nonhuman primates. The experimental measures captured in the in vitro and in vivo model will bespecifically chosen to align with the needs of the modelers. To achieve this goal the proposed consortium willcomplete three specific aims. Specifically the ovarian biology/toxicology team will quantify the physiologicaland toxicant-induced behavior of computationally useful markers of in vivo and in vitro folliculogenesis in mice(Aim 1) and nonhuman primates (Aim 2) while the computational modeling team will construct in silico modelsthat match the physiological behavior of folliculogenesis in each species and predict follicular responses tophthalate insults in both species. Our virtual consortium includes researchers from five institutions and willcreate a transdisciplinary group that includes both experimental and computational expertise. The tightcoupling of these two domains will provide the needed communication pathways to develop translationalmodels for IVIVE as well as cross-species extrapolations in reproductive toxicology.