Platform Session 16. Dying - The Price of Maturation and Aging
Tuesday, July 26, 2005
2:00 PM–4:00 PM
Location: CCQ 204AB
(124) OVARIAN TRANSPLANTATION IN FOLLITROPIN RECEPTOR KNOCKOUT (FORKO) MICE: POTENTIAL REVERSAL OF ENDOCRINE ABNORMALITIES.
Tiwari-Pandey, Rashmi 1, Yang, Yinzhi 1, Aravindakshan, Jayaprakash 1, Sairam, M. Ram 1, 1 Molecular Reproduction Research Laboratory, Clinical Research Institute of Montréal, Montreal, QC, Canada
ABSTRACT- Ovarian transplantation is considered an acceptable alternative for women of reproductive age to preserve or restore fertility during the sterilizing effects of various treatments. The procedure is also used in management of rare wild life. In this investigation we considered the possibility that syngenic transplantation of a normal ovary could restore hormonal balance in an infertile follitropin receptor knockout (FORKO) mouse. Loss of the FSH-R also induces hypergonadotropic-hypogonadism. We have previously demonstrated that female FORKO mice with degenerating ovaries have hormonal imbalances including loss of estrogen and hyperandrogenemia. A single ovary from 3-4 week old wild type mouse was subcutaneously transplanted in the flank of 6-8 weeks old FORKO females. After 15-20 days, vaginal smears were checked at regular intervals and animals were sacrificed after one, two and three months (Gr I, II, and III) in order to investigate the appropriate time for establishment of successful transplantation and restoration of normal endocrine functions. The grafted and host ovaries, uterine horns, blood samples and other organs were collected for various histological, physiological, hormonal and biochemical evaluations. The FSH-R in the grafted wild type ovary responded promptly to pituitary hormones that had been upregulated in host FORKO mice including evidence of super ovulation. The restoration of estrous cycles and response of the previously atrophic host uterus indicated adequate circulating hormones from the graft. In the long term, the grafted ovary continued its function to restore some degree of normalcy in the host ovary. Reduction in atretic follicles in the host ovary and correction of adipose tissue mass also indicated direct estrogenic effects. Cyclin D2, a marker of granulosa cell proliferation marker increased in grafted as well as host ovaries. Ovarian androgen Receptor (AR) protein expression was diminished in Gr III recipients with no change in mRNA. There was also a beneficial effect on ER expression in the ovary. In conclusion, our data indicate that circulating gonadotropins in FORKO mice are fully functional and ovarian transplantation corrects in part the loss of estrogen and diminishes the deleterious effects of hyperandrogenemia on the ovary and other tissues (Supported by CIHR).
KEY WORDS: Transplantation, ovary, follitropin receptor knockout