PARENT SESSION
SLIDE SESSION 18: HORMONE RECEPTORS, STEROID HORMONE ACTION
Chairs: Terry Nett, Leslie Heckert, Dustin Vale-Cruz (Trainee)
Univ Ottawa-Arts Hall 257
1:30 PM-3:30 PM
449
PARTIAL DISRUPTION OF THE FSH RECEPTOR GENE CAUSES PREMATURE OVARIAN FAILURE IN MICE.
Danilovich, Natalia1, Sairam, M. Ram, 1
ABSTRACT- Reproductive aging in female mammals is characterized by a progressive decline in fertility and fecundity. The most important alteration resulting from elevated FSH and decreased inhibin B levels during mid-life in women is depletion of the oocyte pool. Loss of ovarian follicles affects ovarian steroidogenesis, decreases the implantation rate, and causes complications in pregnancy. In this study the overall reproductive performance and structural changes in the ovary of heterozygous (+/-) FOllitropin Receptor KnockOut (FORKO) and wild type mice of different ages were compared. For this purpose estrous cyclicity, the size and composition of follicle population, steroid profiles (T and E2), and ovarian responsiveness (ovulation rate) to gonadotropins were examined at different ages. Gonadotropin concentrations in plasma and pituitary were determined. Selected marker genes (PR-A/PR-B, LH receptor, inhibin, and aromatase) were analyzed by the polymerase chain reaction, Western blotting, and immunohistochemistry using specific antibodies. Heterozygous mice had irregular cyclicity, reduced fertility and fecundity typically resulting in premature reproductive senescence, which occurred by the age of 7 months. The number of ova released into oviducts after superovulation decreased. The plasma steroid and gonadotropin levels exhibited changes associated with ovarian aging. Our findings demonstrate that the loss of even one allele of the FSH receptor gene in heterozygous FORKO mice causes the premature exhaustion of the gonadal reserves accompanied by the age-related changes in the hypothalamic-pituitary axis. These features of FORKO (+/-) mice resemble reproductive failure in middle age women. Therefore, further studies in this model might provide useful insights into the mechanisms underlying ovarian aging. (Supported by the Canadian Institutes of Health Research).
KEY WORDS: Ovarian aging, Ovulation, Gonadotropins, FSH receptor