Ulrike Luderer, M.D., Ph.D.
Assistant Professor

5201 California Avenue (suite 100)
University of California Irvine
Irvine, CA 92697

Lab Tel: (949) 824-3389
Office Tel: (949) 824-8081
Email: uluderer@uci.edu

Reproductive toxicology, developmental toxicology - Research in my laboratory centers on the mechanisms by which chemical toxicants damage the ovary, potentially causing infertility and ovarian cancer, and in understanding differences in ovarian susceptibility to toxicants. We are particularly interested in oxidative stress as a mechanism of ovarian injury and in the modulation of susceptibility to ovarian injury by biotransformation enzymes and antioxidants.

Many known ovarian toxicants are conjugated by the tripeptide glutathione (GSH), and GSH is also a critical detoxification mechanism for reactive oxygen species. Work in my laboratory has demonstrated roles for oxidative stress in mediating both spontaneous and toxicant-induced apoptosis in granulosa cells of ovarian follicles. We showed that biochemical depletion of GSH significantly increased apoptotic follicles in the ovaries of adult rats. We also showed that GSH depletion in cultured follicles reversed the protective, suppressive effect of follicle stimulating hormone on reactive oxygen species and on apoptosis. Our work suggests that the protective effects of follicle stimulating hormone are mediated in part via upregulation of GSH synthesis. Using cultured follicles and granulosa cells, we have shown that increased generation of reactive oxygen species is an early event in the induction of apoptosis by polycyclic aromatic hydrocarbons and by the anticancer drug cyclophosphamide and that depletion of GSH sensitizes to these agents. Ongoing studies are using genetically modified mouse models with specific deficits in GSH synthesis or with more globally decreased antioxidant and biotransformation capacity to understand the roles these play in ovarian susceptibility to toxicant-induced ovarian damage and ovarian cancer.

Recent Publications