Abstract
Folliculogenesis is the process of the activation, development, and atresia (degeneration) of the ovarian follicle, the structure that assists oocyte development. It is essential for ovarian function, as it facilitates ovulation and hormone synthesis, including steroid hormones and Anti-Müllerian Hormone (AMH). AMH is widely used as a serum biomarker to predict primordial follicle numbers, which represent the number of quiescent oocytes remaining in the ovary. AMH is produced in the granulosa cells of follicles and is deemed to inhibit the activation of the primordial follicle, the beginning of follicle development. However, recent studies suggest that AMH could also act on the developing follicles and thus influences the number of developing follicles in the ovary. The aim of this thesis was to investigate how oocyte quality and folliculogenesis were affected by AMH, and also how serum AMH levels correlate to ovarian follicle numbers.
The role of AMH on oocyte quality was examed by embryo culture from AMH-overexpressing mice and reverse transcription quantitative real-time PCR (RT-qPCR) for quantifying transcripts expression. Follicle counting in AMH-knockout mice was used to assess the influence of AMH on the rate of atresia. Serum AMH level measurements and follicle counts during the reproductive lifespan in mice were performed to assess the efficacy of AMH as a predictor of primordial follicle counts.
The in vitro embryo development indicated that elevated AMH exposure causes a moderate reduction in embryo development rates. However, the majority of the embryos derived from oocytes from AMH-overexpressing mice were normal. AMH-knockout ovaries were found to have a significantly higher rate of preantral follicle survival than wild-type mouse ovaries. The analysis of serum AMH levels with ovarian follicle counts confirmed that serum AMH levels are primarily explained by the small and medium antral follicle numbers. The correlation between primordial follicle number and AMH was weak by comparison. This can be explained by the finding that the lack of a strong correlation between antral follicle counts (the AMH producers) and primordial follicle counts.
The findings in this thesis suggest that AMH has a limited effect on oocyte quality but significantly induces follicle death during folliculogenesis. AMH has a predominant influence on small antral follicle numbers, while the AMH-mediated inhibition of primordial follicle activation was found to be a relatively minor influence. The biological function of AMH may not conserve the ovarian reserve to prolong fertility but instead, prevent the antral follicle pool from becoming too large. AMH was confirmed to be a reliable predictor of antral follicle counts but needs more consideration when using primordial follicle counts to predict primordial follicle numbers since antral and primordial follicle numbers were not strongly correlated.