Selected excerpts (no abstract)
Based on these considerations, we hypothesized that the accumulation and function of these cells appeared to be driven by elevated LH, and that the fibrosis suppressed follicular development. To analyze this hypothesis, 6-month-old gcNrg1KO and 12-month-old WT mice were treated for 8-days with a GnRH-antagonist; ovarian histology showed that this regimen caused both the aberrant endocrine cells and fibrotic cells to disappear. Moreover, by 4 days after final GnRH treatment, follicular development had proceeded to the antral stages. The treated mice regained normal, recurrent estrous cycles and continuously delivered pups for at least for 3 months, suggesting that LH-induced fibrosis in the ovarian stroma appears to alter the follicular-stroma microenvironment and restricts follicle growth at the secondary stage. That long-term GnRH antagonist treatment normalized the endocrine functions and matrix conditions of the ovary and improved the fertility documents that the ovarian defects are LH-dependent. Thus, GnRH antagonist treatments might provide a new, noninvasive strategy for improving fertility in a subset of aging women before menopause.