Professor, Environmental and Occupational Health
Public Health

Secondary appointment, Developmental & Cell Biology
School of Biological Sciences

Secondary appointment, Medicine
School of Medicine

Director, Center for Occupational and Environmental Health

Reproductive toxicology, developmental toxicology, ovary, reproductive biology

Jean Spencer Felton Award for Excellence in Scientific Writing, 2017, Western Occupational and Environmental Medicine Association

Diplomate, American Board of Internal Medicine, 1996, 2006
American Board of Preventive Medicine in Occupational and Environmental Medicine, 2000, 2010, 2020

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 2010-2015

California Developmental and Reproductive Toxicant Identification Committee, member since 2012; Chair 2019-present

Our research aims to elucidate the mechanisms by which toxicants and ionizing radiation disrupt reproductive function and to uncover protective mechanisms that prevent reproductive dysfunction. Our earlier work demonstrated a role for reactive oxygen species in mediating spontaneous apoptosis in ovarian follicles deprived of hormonal support and apoptosis of follicles caused by exposure to chemical toxicants.
Ongoing projects include:
Reactive oxygen species, glutathione and ovarian function: Reactive oxygen species, (ROS) are produced during normal ovarian function, and they are also be produced during metabolism of chemical toxicants. We previously discovered that mice genetically deficient in synthesis of the antioxidant tripeptide glutathione (GSH) have accelerated ovarian aging and poor oocyte quality that results in preimplantation embryonic demise. Our recent work has shown that oocytes of GSH deficient mice have elevated levels of mitochondrial ROS, decreased mitochondrial membrane potential, and decreased lipid droplet content. In addition, these mice have an altered serum lipidome, which may be a cause of the decreased oocyte lipid content.
Mechanisms by which in utero exposure to the ubiquitous environmental pollutant benzo[a]pyrene destroys germ cells (eggs) in the developing ovaries of directly exposed embryos and in subsequent generations: We discovered that prenatal exposure to the environmental pollutant benzo[a]pyrene (BaP) induced apoptotic destruction of ovarian germ cells, accelerating reproductive senescence and causing epithelial ovarian tumors in the female offspring. Further, GSH deficiency potentiated the ovarian toxicity of BaP. Most recently, we have shown that ovarian germ cell depletion due to prenatal exposure is transmitted across generations. Specifically, the directly exposed daughters, as well as the great-grand-daughters of females exposed during pregnancy have significantly decreased numbers of ovarian germ cells and the transcriptomes (gene expression) of those ovarian germ cells are masculinized. Current work is focused on deciphering the mechanisms mediating these transgenerational effects.
Effects of space radiation on the ovary: We are investigating the effects of heavy ions, which are components of space radiation, on the ovary. We found that iron and oxygen ions rapidly induced DNA strand breaks, oxidative lipid and protein damage, and apoptosis in ovarian follicles leading to dose-dependent depletion of ovarian follicles, premature ovarian failure, and high prevalence of epithelial ovarian tumors later in life. Currently we are investigating the effects of mixed beams of multiple heavy ions on ovarian tumorigenesis.

Prenatal exposure to benzo[a]pyrene depletes ovarian reserve and masculinizes embryonic ovarian germ cell transcriptome transgenerationally. 2023 Lim J, Shioda T, Malott K, Shioda K, Odajima J, Leon Parada K, Nguyen Julie, Getze S, Lee M, Nguyen Jonathon, Reshel Blakeley S, Trinh V, Truong HA, Luderer U. Scientific Reports online

Best Reproductive and Developmental Toxicology paper of 2023 in Toxicological Sciences
Adolescent exposure to low-dose delta9-tetrahydrocannabinol (THC) depletes the ovarian reserve in female mice. 2023 Lim J, Lee, H-L, Nguyen Julie, Shin J, Getze S, Quach C, Squire E, Jung K-M, Mahler SV, Mackie K, Piomelli D, Luderer U. Toxicological Sciences 193(1): 31-47. online

Malott K, Ortiz L, Lee M, Leon K, Swanson E, Chen J, Lim J, Luderer U. 2022 Gestational Benzo[a]pyrene Exposure Destroys F1 Ovarian Germ Cells via the Mitochondrial Apoptosis Pathway and Diminishes Surviving Oocyte Quality. Toxicological Sciences online

Glutathione Deficiency Decreases Mouse Oocyte Lipid Droplet Stores and Increases Oxidative Stress, Reducing Oocyte Competence. 2022. Malott KF, Reshel S, Ortiz L, Chen J, Lim J, Luderer U. Biology of Reproduction 106(6): 1218-1231 online

Best Paper of the Year 2022 in Particle and Fibre Toxicology
Exposure to Environmentally Relevant Concentrations of Ambient Fine Particulate Matter (PM2.5) Depletes the Ovarian Follicle Reserve and Causes Sex-Dependent Cardiovascular Changes in Apolipoprotein E Null Mice. 2022 Luderer U, Lim J, Ortiz L, Nguyen JD, Shin JH, Allen BD, Liao LS, Malott K, Perraud V, Wingen L, Arechavala RJ, Bliss B, Herman DA, Kleinman MT. Particle and Fibre Toxicology. 19:5 Open access

Sex Difference in Embryonic Gonad Transcriptomes and Benzo[a]pyrene Metabolite Levels after Transplacental Exposure. 2022 Lim J, Ramesh A, Shioda T, Leon Parada K, Luderer U. Endocrinology 163(1). Epub ahead of print, November 3, 2021. doi: 10.1210/endocr/bqab228
(online)

Toxicant effects on mammalian oocyte mitochondria. 2021 Malott KF, Luderer U. Biology of Reproduction. 104(4): 784-793. https://doi.org/10.1093/biolre/ioab002 (online)

Antioxidant Supplementation Partially Rescues Accelerated Depletion of Ovarian Reserve, but Not Oocyte Quality, of Glutathione-Deficient Gclm-/- Mice. 2020 Lim J, Ali S, Liao LS, Nguyen ES, Ortiz L, Reshel S, Luderer U. Biology of Reproduction. 102(5): 1065-1079. https://doi.org/10.1093/biolre/ioaa009 (online)

Reproductive Hazards of Space Travel in Women and Men. Mishra B, Luderer U. Nature Reviews Endocrinology. Published online 14 October 2019. (online).

Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment. 2019. Luderer U, Eskenazi B, Hauser R, Korach KS, McHale CM, Moran F, Rieswijk L, Solomon G, Udagawa O, Zhang L, Zlatnik M, Zeise L, Smith MT. Environmental Health Perspectives. 127(7). DOI: 10.1289//EHP4971 (online)
(Link to webinar on Key Characteristics of Reproductive Toxicants)

In Utero Exposure to Benzo[a]pyrene Induces Ovarian Mutations at Doses that Deplete Ovarian Follicles in Mice. 2019. Luderer U, Meier MJ, Lawson GW, Beal MA, Yauk CL, Marchetti F. Environmental and Molecular Mutagenesis. 60(5):410-420. DOI: 10.1002/em.22261 (online)

Glutathione Deficiency Sensitizes Cultured Embryonic Mouse Ovaries to Benzo[a]pyrene-Induced Germ Cell Apoptosis. 2018. Lim J, Luderer U. Toxicology and Applied Pharmacology. 352:38-45. (online)

Charged Iron Particles Are Potent Inducers of Epithelial Ovarian Tumors. Mishra B, Lawson GW, Ripperdan R, Ortiz L, Luderer U. Radiation Research. 2018. 190(2):142-150. (online)

Associations between Urinary Biomarkers of Polycyclic Aromatic Hydrocarbon Exposure and Reproductive Function in Women. Luderer U, Christensen F, Johnson WO, She J, Ip HSI, Zhou J, Alvaran J, Krieg EF Jr, Kesner JS. Environment International. 2017; 100: 110-120. PMC5291797
(online)

Ovarian Effects of Prenatal Exposure to Benzo[a]pyrene: Roles of Embryonic and Maternal Glutathione Status. Luderer U, Myers MB, Banda M, McKim KL, Ortiz L, Parsons BL. Reproductive Toxicology. 2017, 69:187-195 (online)

Very Low Doses of Heavy Oxygen Ion Radiation Induce Apoptosis in Ovarian Follicles, Causing Premature Ovarian Failure. Mishra B, Ripperdan R, Ortiz L, Luderer U. Reproduction. 2017, 154(2):123-133 (online)

Transitions in Pregnancy Planning in Women Recruited for a Large Prospective Cohort Study. Luderer U, Li T, Fine JP, Hamman RF, Stanford JB, Baker D. Human Reproduction, 2017, 32(6):1325-1333. (online)

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

Exposure to Charged Iron Particles Typical of Space Radiation Induces Premature Ovarian Failure in Mice. Mishra B., Ortiz L, Luderer U. Human Reproduction. 2016; 31(8): 1816-26. DOI: 10.1093/humrep/dew126
(online)

Greater Sensitivity of the Mouse Fetal Ovary than the Fetal Testis to Benzo[a]pyrene-Induced Germ Cell Death. Lim J, Kong W, Lu M, Luderer U. Toxicological Sciences. 2016. 152(2): 372-81. DOI: 10.1093/toxsci/kfw083.
(online)

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

Spatial Characterization of Bioenergetics and Metabolism of Primordial to Preovulatory Follicles in Whole Ex Vivo Murine Ovary. Cinco R, Digman MA, Gratton R, Luderer U. Biology of Reproduction. Epub on September 28, 2016. DOI:10.1095/biolreprod.116.142141
(online)

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; 223(2):260-7. (online)

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

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. (online)

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. (online)

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

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 (online)

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

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.

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

Additional publications: (online)

NIH R01ES020454 Developmental Gene-Environment Interactions and Premature Ovarian Failure

NASA 80NSSC19K1620 Ovarian Cancer and Space Radiation.

NIH R21HD097541 Interactions of Glutathione, Reactive Oxygen Species, and Lipids on Oocyte Mitochondrial Function

Society of Toxicology

American College of Occupational and Environmental Medicine

Endocrine Society

Society for the Study of Reproduction

Cellular and Molecular Biosciences

Environmental Health Sciences

Center for Occupational & Environmental Health

Chao Family Comprehensive Cancer Center

Link to this profile
https://faculty.uci.edu/profile/?facultyId=4535

Last updated
05/24/2024