Ulrike Luderer, MD, PhD, MPH
Director, Environmental Health Sciences Graduate Program
Interim Director, Center for Occupational and Environmental Health
Interim Chief, Division of Occupational and Environmental Medicine




University of California, Irvine
Center for Occupational & Environmental Health
100 Theory, Suite 100
Irvine, CA 92617


Education & Training:

B.S., Brown University
M.D., Ph.D., Northwestern University
M.P.H., University of Washington
Internal Medicine Residency, Evanston Hospital, Northwestern University, Evanston, IL
Occupational and Environmental Medicine Residency, University of Washington, Seattle, WA

Teaching: Preceptor, Occupational and Environmental Medicine Residency Program
Faculty member and director, Environmental Health Sciences Graduate Program
Preceptor, Biological Sciences undergraduate independent study (Bio199)

Research Interests:

Reproductive toxicology, developmental toxicology


Our research is aimed at elucidating the mechanisms by which toxicants and ionizing radiation disrupt reproductive function and the protective mechanisms that prevent reproductive dysfunction. Reactive oxygen species are produced during normal ovarian function, and they may also be produced as a result of toxicant metabolism. Our earlier work demonstrated a role for reactive oxygen species in mediating spontaneous apoptosis in follicles deprived of hormonal support and apoptosis caused by exposure to ovarian toxicants. We discovered that reactive oxygen species increased in ovarian follicles cultured without gonadotropin support prior to any increase in endpoints of apoptosis and that follicle stimulating hormone stimulated synthesis of the antioxidant glutathione (GSH) and suppressed the rise in reactive oxygen species. We further showed that GSH depletion in cultured follicles reversed the protective, suppressive effect of follicle stimulating hormone on reactive oxygen species and on apoptosis. This work provides evidence that the protective effects of follicle stimulating hormone are mediated in part via upregulation of GSH synthesis. We also showed that increased generation of reactive oxygen species is an early event in the induction of apoptosis in cultured follicles or granulosa cells by dimethylbenzanthracene, a polycyclic aromatic hydrocarbon pollutant, and by the anticancer drug cyclophosphamide and ionizing radiation. Furthermore, depletion of GSH potentiated and supplementation of GSH prevented dimethylbenzanthracene, cyclophosphamide, and radiation-induced apoptosis in follicles and granulosa cells. Together these results demonstrate a critical role for GSH in preventing reactive oxygen species initiated apoptosis in ovarian follicles.

To study the roles of GSH in the ovary in vivo, we turned to a mouse model that is genetically deficient in GSH synthesis due to deletion of the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis. We discovered that Gclm null female mice have very low ovarian GSH concentrations resulting in poor oocyte quality, early preimplantation embryonic mortality with small litter sizes, and accelerated onset of ovarian senescence.

We also discovered that Gclm deficiency potentiates the transplacental gonadotoxicity of the environmental pollutant benzo[a]pyrene (BaP). Prenatal exposure to BaP destroyed ovarian germ cells, accelerated reproductive senescence, and caused epithelial ovarian cancer in the female offspring, and Gclm null females were more sensitive than Gclm wild type littermates. Prenatal BaP also impaired spermatogenesis in the male offspring and again Gclm deficient embryos were more sensitive than wild type embryos, but we found that the fetal testis is less sensitive than the fetal ovary to BaP toxicity. We are continuing to investigate the interactions between genetic deficiencies in antioxidant capacity and toxicant exposure in ovarian toxicity, reproductive aging and ovarian cancer.

Our newest project investigates the effects of charged particles, which are components of space radiation, on the ovary. We found that charged iron particles rapidly induced DNA strand breaks, oxidative lipid and protein damage, and apoptosis in ovarian follicles leading to dose-dependent depleiton of ovarian follicles and premature ovarian failure. Our results show that the ovary is exquisitely sensitive to charged iron particles, with a very low dose of 0.05 Gray depleting the ovarian follicle reserve by 50%. Ongoing studies are further investigating the mechanisms by which charged particles destroy ovarian follicles and cause ovarian tumors.

Clinical & Consulting: Occupational and Environmental Medicine and Toxicology. Special interest in reproductive and developmental toxicology.

Recent Publications:

Mishra B., Ortiz L, Luderer U. Exposure to Charged Iron Particles Typical of Space Radiation Induces Premature Ovarian Failure in Mice. Human Reproduction. 2016; Epub ahead of print. DOI: 10.1093/humrep/dew126 (online)

Lim J, Kong W, Lu M, Luderer U. Greater Sensitivity of the Mouse Fetal Ovary than the Fetal Testis to Benzo[a]pyrene-Induced Germ Cell Death. Toxicological Sciences. 2016. Epub ahead of print. DOI: 10.1093/toxsci/kfw083. (online)

Lim J, Nakamura BN, Mohar I, Kavanagh TJ, Luderer U. Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure. Endocrinology. 2015; 156(9):3329-3343. Epub June 17, 2015. DOI: 10.1210/en.2015-1206. (online)

Lim J, Ortiz L, Nakamura BN, Hoang YD, Banuelos J, Flores VN, Chan JY, Luderer U. Effects of Deletion of the Transcription Factor Nrf2 and Benzo[a]pyrene Treatment on Ovarian Follicles and Ovarian Surface Epithelial Cells in Mice. Reproductive Toxicology. 2015; 58: 24-32. Epub August 3, 2015. DOI: 10.1016/j.reprotox.2015.07.080. (online)

Ortiz L, Nakamura BN, Li X, Blumberg B, Luderer U. In Utero Exposure to Benzo[a]pyrene Increases Adiposity and Causes Hepatic Steatosis in Female Mice, and Glutathione Deficiency Is Protective. Toxicology Letters. 2013; 223(2):260-7. (online)

Luderer U, Kesner JS, Fuller JM, Krieg EF Jr, Meadows JW, Tramma SL, Yang H, Baker D. Effects of Gestational and Lactational Exposure to Heptachlor Epoxide on Age at Puberty and Reproductive Function in Men and Women. Environmental Research. 2013, 121:84-94. doi: 10.1016/j.envres.2012.11.001. Epub 2012 Nov 26.

Lim J, Lawson GW, Nakamura BN, Ortiz L, Hur JA, Kavanagh TJ, Luderer U. Glutathione-Deficient Mice have Increased Sensitivity to Transplacental Benzo[a]pyrene-Induced Premature Ovarian Failure and Ovarian Tumorigenesis.Cancer Research. 2013; 73(2):908-917.10.1210/en.2015-1206. (online)

Nakamura BN, Mohar I, Lawson GW, Hoang YD, Cortés MM, Ortiz L, Patel R, Rau BA, McConnachie L, Kavanagh TJ, Luderer U. Increased Sensitivity to Testicular Toxicity of Transplacental Benzo[a]pyrene Exposure in Male Glutamate Cysteine Ligase Modifier Subunit Knockout (Gclm-/-) Mice. Toxicological Sciences. 2012, 126(1):227-41. (online)

Devine PJ, Perreault SD, Luderer U. Roles of Reactive Oxygen Species and Antioxidants in Ovarian Toxicity. Biology of Reproduction. 2012, 86(2):27. doi: 10.1095/biolreprod.111.095224. Print 2012 Feb.

Lim J, Luderer U. Oxidative Damage Increases and Antioxidant Gene Expression Decreases with Aging in the Mouse Ovary. Biology of Reproduction. 2011, 84:775-782.

Nakamura BN, Fielder TJ, Hoang YD, Lim J, McConnachie LA, Kavanagh TJ, Luderer U. Lack of Maternal Glutamate Cysteine Ligase Modifier Subunit (Gclm) Decreases Oocyte Glutathione Concentrations and Disrupts Preimplantation Development in Mice. Endocrinology. 2011; 152: 2806-2815. (online)

Nakamura BN, Lawson G, Chan JY, Banuelos J, Cortés MM, Hoang YD, Ortiz L, Rau BA, Luderer U. Knockout of the Transcription Factor Nrf2 Disrupts Spermatogenesis in an Age-Dependent Manner. Free Radical Biology and Medicine. 2010, 49:1368-1379.

Hoang YD, Nakamura BN, Luderer U. Follicle-Stimulating Hormone and Estradiol Interact to Stimulate Glutathione Synthesis in Rat Ovarian Follicles and Granulosa Cells. Biology of Reproduction. 2009, 81:636-646.

Cortes-Wanstreet MM, Giedzinski E, Limoli CL, Luderer U. Overexpression of Glutamate Cysteine Ligase Protects Human COV434 Granulosa Tumor Cells against Oxidative and Gamma-Radiation Induced Cell Death. Mutagenesis. 2009, 24:211-224.

Tsai-Turton M, Nakamura BN, Luderer U. Induction of Apoptosis by 9,10-Dimethyl-1,2-benzanthracene (DMBA) in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione. Biology of Reproduction. 2007, 77:442-451.

Tsai-Turton M, Luong BT, Tan Y, Luderer U. Cyclophosphamide-Induced Apoptosis in COV434 Human Granulosa Cells Involves Oxidative Stress and Glutathione Depletion. Toxicological Sciences. 2007, 98: 216-230.

Tsai-Turton M, Luderer U. Opposing Effects of Glutathione Depletion and FSH on Reactive Oxygen Species and Apoptosis in Cultured Preovulatory Rat Follicles. Endocrinology. 2006, 147: 1224-1236.

Hoang YD, Avakian AP, Luderer U. Minimal Ovarian Upregulation of Glutamate Cysteine Ligase Expression in Response to Suppression of Glutathione by Buthionine Sulfoximine. Reproductive Toxicology. 2006, 21:186-196.

Tsai-Turton M, Luderer U. Gonadotropin Regulation of Glutamate Cysteine Ligase Catalytic and Modifier Subunit Expression in the Rat Ovary is Subunit and Follicle Stage-Specific. American Journal of Physiology Endocrinology and Metabolism. 2005, 289: E391-E402.

Luderer U, Bushley, A, Stover, BD, Bremner WJ, Faustman EM, Takaro TK, Checkoway H, Brodkin CA. Effects of Occupational Solvent Exposure on Reproductive Hormone Concentrations and Fecundability in Men. American Journal of Industrial Medicine. 2004, 46:614-626.

Lawson G, Luderer U. Gestational and Lactational Exposure to Heptachlor Does Not Alter Reproductive System Development in Rats. Veterinary and Human Toxicology. 2004, 46:113-118.

Lopez SG, Luderer U. Effects of Cyclophosphamide and Buthionine Sulfoximine on Ovarian Glutathione and Apoptosis. Free Radical Biology and Medicine. 2004, 36:1366-1377.

Luderer U, Tornero-Velez R, Shay T, Rappaport SM, Heyer N, Echeverria D. Temporal Association between Serum Prolactin Concentration and Exposure to Styrene. Occupational and Environmental Medicine. 2004, 61:325-333.

Luderer U, Diaz D, Faustman EM, Kavanagh TJ. Localization of Glutamate Cysteine Ligase Subunit mRNA within the Rat Ovary and Relationship to Follicular Atresia. Molecular Reproduction and Development. 2003, 65:254-261.

Luderer U, Kavanagh TJ, White CC, Faustman EM. Gonadotropin Regulation of Glutathione Synthesis in the Rat Ovary. Reproductive Toxicology. 2001, 15:495-504.

Luderer U, Morgan MS, Brodkin, CA, Kalman DA, Faustman EM. Reproductive Endocrine Effects of Acute Toluene Exposure in Men and Women, Occupational and Environmental Medicine. 1999, 56:657-666.

Luderer U, Burgess JL, Polifka JE, Robertson WO. Calls on Reproductive and Developmental Toxicants to a Regional Poison Center. Veterinary and Human Toxicology. 1999, 41: 42-46.

Luderer U, Strobl FJ, Levine JE, Schwartz NB. Differential Gonadotropin Responses to N-methyl-D,L-aspartate in Metestrous, Proestrous and Ovariectomized Rats. Biology of Reproduction. 1993, 48:857-866.