UC Irvine

ABSTRACT OF THE THESIS

By

Sanjiwani Meharda

Master of Science in Environmental Health Science

University of California, Irvine,2016

Professor Ulrike Luderer, Chair

In contrast to gametogenesis in males, oocytes in females are not continually replenished during reproductive life. Exposure to ovotoxicants during or after embryogenesis can lead to irreversible ovarian dysgenesis or premature ovarian failure (POF).

Benzo [a] pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) and a component of air pollution. PAHs are formed as a result of incomplete combustion of organic materials and are ubiquitous environmental contaminants. Found in cigarette smoke, polycyclic aromatic hydrocarbons are “toxic to and destructive to oocytes in several animal test systems.” Men and women who smoke have decreased fertility.

Our study for the first time uses the lacZ transgenic MutaTMMouse, mouse model to study female reproductive consequences of prenatal exposure to BaP

Pregnant transgenic MutaMouse were treated with 0, 10, 20 or 40 mg/kg/d BaP orally from gestational day 7 through 16, which represents the major period of organogenesis. The F1 female offspring were euthanized at 10 wk. of age and ovaries were processed for differential ovarian follicle counting.

Transplacental BaP exposure caused very significant dose-related decreases in primordial, primary and secondary follicles in the ovaries of F1 MutaMice. There was prominent ovarian tissue destruction at the higher doses of BaP exposure. Our results show that maternal exposure to BaP during gestation is highly damaging to the developing ovaries of the F1 female offspring in Muta mice as it is in other mouse strains that have been studied. Therefore, this model is an excellent model not only for observing the mutation effects but also for showing the reproductive effects.

Our findings in the mouse are relevant to humans, as ovarian development in humans and mice is very similar. Increasing evidence regarding PAH exposure and its harmful effects leads us to believe that additional regulations to reduce PAH exposure are needed at the government level. In addition, campaigns to increase awareness among the general population about PAHs are needed, as “Prevention is the key”.