College of Science and Health Theses and Dissertations

Date of Award

Spring 6-13-2014

Degree Type


Degree Name

Master of Science (MS)



First Advisor

Margaret Silliker, Ph.D.

Second Advisor

Jingjing Kipp, Ph.D.

Third Advisor

Carolyn Martineau, Ph.D.


The active metabolite of vitamin A, retinoic acid, is vital to several physiological functions, and is most notably associated with vision and organ development Its role in the male reproductive system is well understood, but studies in female reproduction are lacking. Recent studies show that Cyp26b1, a retinoic acid degrading enzyme, is expressed highly in the Day1-10 mouse ovary. This time point correlates with establishment of the primordial follicle pool. In vitro studies show that both retinoic acid and R115866, an agent that blocks retinoic acid metabolism, increase cell proliferation. Because of this, we hypothesized that retinoic acid plays a critical role in the development of the mouse ovary.

To test this hypothesis, we placed female mice on a vitamin A deficient diet over a time course beginning from gestation. Endogenous retinoic acid levels were also increased by injection of R115866 at either 0.5 or 1.0 mg/kg during the first 7 days after birth when the levels of Cyp26b1 expression are high. At day 19, week 7, and week 15, ovaries were harvested for morphological and RT-PCR studies. Our results show that animals on a vitamin A-deficient diet or injected with R115866 developed a variety of ovarian pathologies at day 19, week 7, and week 15. Long term pathologies were also observed in mice that were placed on a vitamin A-deficient diet for 16 weeks then allowed to recover for one year Overall, our results indicate that retinoic acid plays an important role in the development ofthe mouse ovary and that balanced retinoic acid

levels early in development are needed for the health of ovaries. In addition, the effect of early vitamin A deficiency has long lasting consequences that cannot be corrected by a subsequent normal diet