The female germline is exceedingly sensitive to the exposure to toxicants, including those found in the environment and those used to treat diseases such as cancer. Oocytes are one of the longest living cells in the mammalian female body, and may have prolonged exposure to exogenous and endogenous toxicants that can cause DNA damage and instability. For the females of many species, perturbations caused by toxicants result not only in reproductive disorders, such as infertility and premature ovarian failure, but also in non-reproductive metabolic and health-related diseases. Of further concern is that these adverse effects can also be passed onto offspring via genetic and nongenetic (epigenetic) inherited damage sustained in the oocytes. Using a combination of genetic mouse models, chemotherapies, radiation and environmentally relevant concentrations of pesticides my work aims to i) identify mechanism’s involved in preserving fertility, ii) understand how genome integrity is maintained in oocytes and iii) determine if mechanisms used to preserve fertility are safe with respect to genome integrity and future generation’s health. Understanding the effects of life saving chemotherapies and drugs in addition to pervasive environmental toxicants on the ovary, oocytes, and female fertility is vital, as perturbations can result in reproductive disorders and systemic diseases in current and future generations.