This project seeks to understand the physiology and pathophysiology of ovarian follicle development and function, and to thereby develop clinical diagnostic an therapeutic applications for women with ovulatory disorders. During this period we have focused on premature ovarian failure, a condition which prematurely terminates fertility in 1% of women. We have particular interest in autoimmune-mediated ovarian failure and seek to improve our understanding of this condition through clinical research and through basic immunologic research employing a mouse model of autoimmune ovarian failure (induced by neonatal thymectomy). During this period we have demonstrated that during a 4 month observation period with serial serum estradiol measurements we can detect ovarian follicle function in approximately 50% of patients with premature ovarian failure. Furthermore, almost 20% of these patients ovulated during this observation as determined by serial progesterone levels. We completed a controlled evaluation of gonadotropin suppression as a means to induce remission in patients with ovarian failure. We demonstrated that four months of gonadotropin suppression with a gonadotropin releasing hormone agonist was no more effective than placebo in inducing return of ovarian function. During the current year we have continued our work in a mouse model of autoimmune lymphocytic oophoritis. We are defining the time course and histologic location of the ovarian lymphocytic infiltrate. We have developed and validated a technique to localize mouse lymphocytes in the ovary by using immunohistochemistry and a monoclonal antibody against a surface protein specific to mouse lymphocytes (CD45). We plan to continue to define the pathogenesis of autoimmune ovarian failure in the neonatally thymectomized mouse by using immunohistochemical techniques to characterize the initial events in this process, and by using cell culture techniques to assess T lymphocyte proliferation in response to ovarian antigens. In te coming tears we also plan to evaluate other treatments for premature ovarian failure by controlled prospective clinical trials and to assess the pathophysiologic role of the immunoglobulins and T lymphocytes in autoimmune premature ovarian failure.
| Popat, Vaishali B; Calis, Karim A; Vanderhoof, Vien H et al. (2009) Bone mineral density in estrogen-deficient young women. J Clin Endocrinol Metab 94:2277-83 |
| Hubayter, Ziad R; Popat, Vaishali; Vanderhoof, Vien H et al. (2009) A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency. Fertil Steril : |
| Kalantaridou, Sophia N; Vanderhoof, Vien H; Calis, Karim A et al. (2008) Sexual function in young women with spontaneous 46,XX primary ovarian insufficiency. Fertil Steril 90:1805-11 |
| McConkie-Rosell, Allyn; Abrams, Liane; Finucane, Brenda et al. (2007) Recommendations from multi-disciplinary focus groups on cascade testing and genetic counseling for fragile X-associated disorders. J Genet Couns 16:593-606 |
| Ventura, June L; Fitzgerald, O Ray; Koziol, Deloris E et al. (2007) Functional well-being is positively correlated with spiritual well-being in women who have spontaneous premature ovarian failure. Fertil Steril 87:584-90 |
| Wittenberger, Michael D; Hagerman, Randi J; Sherman, Stephanie L et al. (2007) The FMR1 premutation and reproduction. Fertil Steril 87:456-65 |
| Armstrong, Alicia Y; Calis, Karim A; Nelson, Lawrence M (2007) Do survivors of childhood cancer have an increased incidence of primary ovarian insufficiency? Nat Clin Pract Endocrinol Metab 3:326-7 |
| Di Pasquale, Elisa; Rossetti, Raffaella; Marozzi, Anna et al. (2006) Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab 91:1976-9 |
| Tung, Joyce Y; Rosen, Mitchell P; Nelson, Lawrence M et al. (2006) Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in infertile women and men. Reprod Biol Endocrinol 4:40 |
| Corrigan, Emily C; Nelson, Lawrence M; Bakalov, Vladimir K et al. (2006) Effects of ovarian failure and X-chromosome deletion on body composition and insulin sensitivity in young women. Menopause 13:911-6 |
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