THE DISRUPTION OF THE BLOOD FOLLICLE BARRIER IN OVARIAN FOLLICULAR CYST DEVELOPMENT: REGULATION BY NITRIC OXIDE
Cystic formation of ovarian follicles is the leading cause of infertility among livestock and humans. In livestock, primarily dairy cattle and swine, the disorder is referred to as Cystic Ovarian Disease (COD) and in humans it is known as Polycystic Ovary Syndrome (PCOS). Features of ovarian cyst disorders include chronic anovulation, increased luteinizing hormone (LH) levels, hyperandrogenism, and multiple ovarian follicular cysts that have surpassed ovulatory size, but have failed to ovulate. Although the cause of this disorder is unknown, emerging evidence from human blood flow studies has implicated the ovarian vasculature in the pathogenesis of COD/PCOS. To this end, we created a mouse model by chronic infusion of human chorionic gonadotropin (hCG) to investigate the blood follicle barrier (BFB) in the pathogenesis of follicular cyst disorders. These mice exhibited multiple follicular cysts, elevated testosterone levels, and altered ovulatory capacity. The BFB of cystic follicles was unresponsive to ovulatory surges and thereby defective. Because the BFB was responsive to exogenous nitric oxide, it was hypothesized that Nitric Oxide (NO) plays a role in the vasculature of follicular cysts. Subsequently, mice were co-infused with hCG and Nitric Oxide Synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), to inhibit NO production. In these mice, complete cystic formation and loss of BFB reactivity was prevented and testosterone and NO levels were reduced. Thus, this mouse model has proven to be a successful laboratory tool to study COD/PCOS. From these studies, it is clear that the vasculature is involved in cystic formation and one of the key vasoactive components is nitric oxide. These results suggest that diminishing or eliminating NO synthesis may serve as a meaningful therapy for COD/PCOS patients. In conclusion, these studies have made a valuable contribution to the endocrine field and may have a significant impact on future investigations of COD/PCOS and related disorders.
School:University of Cincinnati
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:ovary blood follicle barrier nitric oxide polycystic syndrome cystic ovarian disease
Date of Publication:01/01/2000