Reproductive and Toxicological Genetics

Individual humans, as well as, strains of laboratory animals differ markedly in sensitivity to fertility drugs, estrogens and environmental toxicants. The tremendous variability between individuals in sensitivity to hormonally active compounds presents major problems to regulating fertility and improving reproductive health. While studies in laboratory animals have shown that much of the individual variability in sensitivity to reproductive hormones and endocrine disruptors is genetic, few of the genes controlling these traits have been identified.

This site is dedicated to improving reproductive health and achieving the desired level of fertility by identifying genetic markers for sensitivity to fertility drugs, estrogens and endocrine disruptors. Identification of genetic markers for sensitivity to reproductive hormones will enable hormonal treatments to be tailored to each individual's genotype, thereby enhancing reproductive health and achieving the desired level of fertility while minimizing deleterious hormonal side-effects. Identification of genetic markers for sensitivity to endocrine disruptors will also enhance the detection, prevention and treatment of environmentally induced infertility and reproductive disease.

Genetic Sensitivity to Fertility Drugs: Genetic markers for sensitivity to the induction of ovulation by fertility drugs, i.e. gonadotropins, is key to optimizing fertility treatments while avoiding the serious health risks of ovarian hyperstimulation and multiple pregnancy. Studies in our laboratory have discovered major 6 to 16-fold genetic differences between strains of mice in sensitivity to the hormonal induction of ovulation, estrogen production and aromatase activity. We have used the laboratory mouse to map genes and develop congenic strain models uniquely suited for identifying genes controlling normal variation in the induction of ovulation and ovarian estrogen production. Please click on the above section title to learn more.

Genetic Susceptibility to Endocrine Disruption by Estrogen and Environmental Estrogens : Several studies have shown that many environmental chemicals can mimic estrogens and disrupt reproductive development and fertility. We have discovered and characterized major genetic differences in sensitivity to estrogen. This includes greater than 16 fold-differences between strains of mice in susceptibility to the disruption of sperm maturation and male / female reproductive development by estrogens. This also includes strain differences in sensitivity to the effects of Bisphenol A on reproductive development. These and other published studies have raised concern that environmental estrogens may be disrupting reproductive development and reducing fertility, especially in sensitive individuals. Please click on the above section title to learn more.

Genetic Sensitivity to Estrogens: Genetic markers for sensitivity to Estrogens and/or Selective Estrogen Receptor Modulators (SERMs) are needed to enhance the optimization of contraceptive treatments in young women and Hormone Replacement Therapy (HRT) in postmenopausal women. To enhance these studies, Dr. Spearow has, in collaboration with Dr. Susan Nagel, bred the Estrogen Receptor action INdicator (ERIN) reporter transgene on to estrogen sensitive and on to estrogen resistant mouse strain genetic backgrounds. Please click on the above section title to learn more.

Effects of Environmental Tobacco Smoke on Sperm Genetic and Oxidative Damage: Environmental exposure to several different chemicals has been associated with developmental defects or infertility. Current studies are being conducted in the laboratories of Dr. Cathy Vandevoort and Dr. Marion Miller examining the effects of Environmental Tobacco Smoke on Sperm Genetic and Oxidative Damage endpoints.

Contributions to this Research

Please note that this site is still under construction.

Note that the information and opinions stated on this web site do not represent the position of the California EPA.