Roles of Retinoic Acid and CYP26B1 in Regulating Ovarian Follicle Development

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 561-585-Ovarian & Uterine Function II
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-567
Shruti Kmath*, Mike Akroush, Michael Demczuk and Jingjing Kipp
DePaul University, Chicago, IL
Retinoic acid (RA), an active metabolite of vitamin A, is involved in tissue organization, patterning and growth. Although RA has been shown to regulate granulosa cell differentiation and oocyte development in domestic animals, information on its roles in ovarian follicle development is very limited. CYP26B1 is a key enzyme that degrades RA. We have demonstrated that RA and the CYP26 inhibitor R115866 stimulate granulosa cell growth. To further investigate the functions of RA and CYP26B1 in the ovary, we examined their roles in follicle growth/survival using an ex vivo follicle culture system and an in vivo dietary vitamin A-deprivation animal model. Secondary follicles isolated from CD-1 mice were cultured and treated with DMSO (control), FSH (positive control), RA, R115866, or liarozole, an RA metabolism inhibitor, for 4 days with follicle diameters measured daily. FSH and liarozole both significantly induced follicle growth. R115866 also stimulated follicle growth dose-dependently. The effect of RA was less robust as compared to R115866, suggesting high activity of RA degrading enzymes in these follicles. To investigate in vivo functions of RA, CD-1 pregnant females were fed with either a vitamin A deficient diet (VA-) or a control diet, and at weaning, female pups were maintained on their respective diet. Ovary and blood samples from these female pups were collected at days-1, 6, 10, and 19 and weeks-7 and 15. Morphological studies reviewed no obvious ovarian abnormality at days 1-10 in VA- ovaries. At day 19, total follicle numbers were reduced while atretic follicle numbers were increased in VA- ovaries. At week 7 or 15, the number of corpora lutea was significantly lower in the VA- group as compared to control. In addition, cystic ovarian bursa in all animals, hemorrhagic antral follicles in some animals, increased serum testosterone levels and decreased serum FSH levels were also observed in the VA- group at week 15. We are currently examining mechanisms underlying the observed ovarian pathologies. Overall, this study suggests that RA is critical for follicle growth/survival at later stages of follicle development and ovulation and CYP26B1 inhibits the growth of secondary follicles. We conclude that RA and CYP26B1 are important factors that play a role in the regulation of ovarian follicle development and ovarian functions.

Kipp JL, Golebiowski A, Rodriguez G, Demczuk M, Kilen S, and Mayo KE. (2011) Gene Expression Profiling Reveals Cyp26b1 to be an Activin Regulated Gene Involved in Ovarian Granulosa Cell Proliferation. Endocrinology. 152(1):303-12.

Nothing to Disclose: SK, MA, MD, JK

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Sources of Research Support: Supported by Kipp Start Up Fund and URC/Summer Research/Graduate Student Research Grants from DePaul University.