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Ulrike Luderer

Professor, Medicine
School of Medicine

Secondary appointment
School of Biological Sciences

Director, Environmental Health Sciences Graduate Program, Medicine
School of Medicine

Secondary appointment
Public Health

M.D., Northwestern University


Ph.D.,, Northwestern University, Reproductive Endocrinology


M.P.H., University of Washington

Phone: (949) 824-8641
Fax: (949) 824-2345
Email: uluderer@uci.edu

University of California, Irvine
Center for Occupational and Environmental Health
100 Theory Drive, Suite 100
Mail Code: 1830
Irvine, CA 92617

picture of Ulrike  Luderer

Research
Interests
Reproductive toxicology, developmental toxicology
   
Academic
Distinctions
Diplomate, American Board of Internal Medicine, 1996, 2006
American Board of Preventive Medicine in Occupational and Environmental Medicine, 2000, 2010

Appointments:
National Research Council, Subcommittee for the Review of the Risk Assessment of Methyl Bromide, Jul 99-May 00.

U.S. Environmental Protection Agency Science Advisory Board Environmental Health Committee, Oct 00-Sep 06.

Center for the Evaluation of Risks to Human Reproduction, National Toxicology Program, Expert Panel on 1- and 2-Bromopropane, Sept 01-Jan 02.

Center for the Evaluation of Risks to Human Reproduction, National Toxicology Program, Chair of Expert Panel on Styrene, Jan-Jun 05.

California Environmental Contaminant Biomonitoring Program Scientific Guidance Panel. Member, Aug 2007-present. Chair May 2010-present

California Developmental and Reproductive Toxicant Identification Committee, 2012-present
   
Research
Abstract
Current research interests

ANTIOXIDANT PROTECTIVE MECHANISMS IN OVARIAN FOLLICLES
Our research is aimed at elucidating the mechanisms by which toxicants disrupt reproductive function and the protective mechanisms that prevent toxicant-induced 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 (Tsai-Turton and Luderer, 2006). 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 (Tsai-Turton and Luderer, 2006). 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 was an early event in the induction of apoptosis in cultured follicles by dimethylbenzanthracene, a polycyclic aromatic hydrocarbon pollutant (Tsai-Turton et al, 2007a) and in the induction of apoptosis in cultured granulosa cells by the anticancer drug cyclophosphamide (Tsai-Turton et al, 2007b) and by ionizing radiation (Cortes-Wanstreet et al, 2008). 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.
More recently, we have utilized 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 poor oocyte quality with very low oocyte GSH concentrations and that this leads to early preimplantation embryonic mortality and small litter sizes. Prenatal exposure to the environmental pollutant benzo[a]pyrene 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 (Lim et al, 2013). We are continuing to investigate the interactions between genetic deficiencies in antioxidant capacity and toxicant exposure in ovarian toxicity, reproductive aging and ovarian cancer.
   
Publications In Utero Exposure to Benzo[a]pyrene Increases Adiposity and Causes Hepatic Steatosis in Female Mice, and Glutathione Deficiency Is Protective. Ortiz L, Nakamura BN, Li X, Blumberg B, Luderer U. Toxicology Letters. 2013. E-pub ahead of print. doi:10.1016/j.toxlet.2013.09.017
   
  Glutathione-Deficient Mice have Increased Sensitivity to Transplacental Benzo[a]pyrene-Induced Premature Ovarian Failure and Ovarian Tumorigenesis.Lim J, Lawson GW, Nakamura BN, Ortiz L, Hur JA, Kavanagh TJ, Luderer U. Cancer Research. 2013; 73(2):908-917. DOI: 10.1158/0008-5472.CAN-12-3636
   
  Effects of Gestational and Lactational Exposure to Heptachlor Epoxide on Age at Puberty and Reproductive Function in Men and Women.Luderer U, Kesner JS, Fuller JM, Krieg EF Jr, Meadows JW, Tramma SL, Yang H, Baker D. Environmental Research. 2013; 121: 84-94. DOI: 10.1016/j.envres.2012.11.001
   
  Increased sensitivity to testicular toxicity of transplacental benzo[a]pyrene exposure in male glutamate cysteine ligase modifier subunit knockout (Gclm-/-) mice. Nakamura BN, Mohar I, Lawson GW, Hoang YD, Cortés MM, Ortiz L, Patel R, Rau BA, McConnachie L, Kavanagh TJ, Luderer U. Toxicological Sciences. 2012; 126(1): 227-241. DOI: 10.1093/toxsci/kfs017.
   
  Roles of Reactive Oxygen Species and Antioxidants in Ovarian Toxicity. Devine PJ, Perreault SD, Luderer U. Biology of Reproduction. 2012; 86(2): 27, 1-10. DOI: 10.1095/biolreprod.111.095224
   
  Oxidative Damage Increases and Antioxidant Gene Expression Decreases with Aging in the Mouse Ovary. Lim J, Luderer U. Biology of Reproduction. 2011; 84: 775-782
   
  Lack of Maternal Glutamate Cysteine Ligase Modifier Subunit (Gclm) Decreases Oocyte Glutathione Concentrations and Disrupts Preimplantation Development in Mice. Nakamura BN, Fielder TJ, Hoang YD, Lim J, McConnachie LA, Kavanagh TJ, Luderer U. Endocrinology. 2011; 152: 2806-2815
   
  Knockout of the Transcription Factor Nrf2 Disrupts Spermatogenesis in an Age-Dependent Manner. Nakamura BN, Lawson G, Chan JY, Banuelos J, Cortés MM, Hoang YD, Ortiz L, Rau BA, Luderer U. 2010, Free Radical Biology and Medicine. 49:1368-1379.
   
  Follicle-Stimulating Hormone and Estradiol Interact to Stimulate Glutathione Synthesis in Rat Ovarian Follicles and Granulosa Cells. Hoang YD, Nakamura BN, Luderer U. 2009 Biology of Reproduction. 81:636-646.
   
  Overexpression of Glutamate Cysteine Ligase Protects Human COV434 Granulosa Tumor Cells against Oxidative and Gamma-Radiation Induced Cell Death. Cortes-Wanstreet MM, Giedzinski E, Limoli CL, Luderer U. 2009 Mutagenesis 24:211-224
   
  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.Tsai-Turton M, Nakamura BN, Luderer U. Biology of Reproduction. 2007, 77: 442-451.
   
  Cyclophosphamide-Induced Apoptosis in COV434 Human Granulosa Cells Involves Oxidative Stress and Glutathione Depletion. Tsai-Turton M, Luong BT, Tan Y, Luderer U. Toxicological Sciences. 2007 98: 216-230.
   
  Opposing Effects of Glutathione Depletion and FSH on Reactive Oxygen Species and Apoptosis in Cultured Preovulatory Rat Follicles. Tsai-Turton M, Luderer U. Endocrinology. 2006, 147: 1224-1236.
   
  Minimal Ovarian Upregulation of Glutamate Cysteine Ligase Expression in Response to Suppression of Glutathione by Buthionine Sulfoximine. Hoang YD, Avakian AP, Luderer U. Reproductive Toxicology. 2006, 21:186-196.
   
  Gonadotropin Regulation of Glutamate Cysteine Ligase Catalytic and Modifier Subunit Expression in the Rat Ovary is Subunit and Follicle Stage-Specific. Tsai-Turton M, Luderer U. American Journal of Physiology Endocrinology and Metabolism. 2005, 289: E391-E402.
   
  Effects of Occupational Solvent Exposure on Reproductive Hormone Concentrations and Fecundability in Men. Luderer U, Bushley, A, Stover, BD, Bremner WJ, Faustman EM, Takaro TK, Checkoway H, Brodkin CA. American Journal of Industrial Medicine. 2004, 46:614-626
   
  Gestational and Lactational Exposure to Heptachlor Does Not Alter Reproductive System Development in Rats. Lawson G, Luderer U. Veterinary and Human Toxicology. 2004, 46:113-118.
   
  Effects of cyclophosphamide and buthionine sulfoximine on ovarian glutathione and apoptosis. Lopez SG, Luderer U. Free Radical Biology and Medicine. 2004, 36:1366-1377.
   
  Temporal Association between Serum Prolactin Concentration and Exposure to Styrene. Luderer U, Tornero-Velez R, Shay T, Rappaport SM, Heyer N, Echeverria D. Occupational and Environmental Medicine. 2004, 61:325-333.
   
  Localization of Glutamate Cysteine Ligase Subunit mRNA within the Rat Ovary and Relationship to Follicular Atresia, Luderer U, Diaz D, Faustman EM, Kavanagh TJ. Molecular Reproduction and Development. 2003, 65:254-261
   
  Gonadotropin Regulation of Glutathione Synthesis in the Rat Ovary, Luderer U, Kavanagh TJ, White CC, Faustman EM, Reproductive Toxicology., 2001, 15:495-504
   
  Reproductive endocrine effects of acute toluene exposure in men and women., Luderer U, Morgan MS, Brodkin, CA, Kalman DA, Faustman EM, Occupational and Environmental Medicine, 1999, 56: 657-666
   
  Differential gonadotropin responses to N-methyl-D,L-aspartate in metestrous, proestrous and ovariectomized rats, Luderer U, Strobl FJ, Levine JE, Schwartz NB, Biology of Reproduction, 1993, 48: 857-866
   
Professional
Societies
Society of Toxicology
American College of Occupational and Environmental Medicine
Endocrine Society
Society for the Study of Reproduction
   
Graduate Programs Environmental Toxicology

Cellular and Molecular Biosciences

   
Research Centers Center for Occupational & Environmental Health
   
Chao Family Comprehensive Cancer Center
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=4535
   
Last updated 10/22/2013