Abstract
The current study was designed to investigate the actions of Anti-Müllerian Hormone (AMH) on primordial follicle assembly. Ovarian primordial follicles develop from the breakdown of oocyte nests during fetal development for the human and immediately after birth in rodents. AMH was found to inhibit primordial follicle assembly and decrease the initial primordial follicle pool size in a rat ovarian organ culture. The AMH expression was found to be primarily in the stromal tissue of the ovaries at this period of development, suggesting a stromal-epithelial cell interaction for primordial follicle assembly. AMH was found to promote alterations in the ovarian transcriptome during primordial follicle assembly with over 200 genes with altered expression. A gene network was identified suggesting a potential central role for the Fgf2/Nudt6 antisense transcript in the follicle assembly process. A number of signal transduction pathways are regulated by AMH actions on the ovarian transcriptome, in particular the transforming growth factor – beta (TGFß) signaling process. AMH is the first hormone/protein shown to have an inhibitory action on primordial follicle assembly. Due to the critical role of the primordial follicle pool size for female reproduction, elucidation of factors, such as AMH, that regulate the assembly process will provide insights into potential therapeutics to manipulate the pool size and female reproduction.
Highlights
The functional unit within mammalian ovaries is the ovarian follicle
We investigate the role of AntiMullerian hormone (AMH), referred to as Mullerian Inhibitory Substance (MIS), on the follicle assembly process
The number of oocytes that had been assembled into follicles was determined, as was the number of oocytes that remained un-assembled in nests
Summary
The functional unit within mammalian ovaries is the ovarian follicle. Each follicle has one oocyte that is surrounded by granulosa cells and theca cells [1,2]. When ovarian follicles are first formed, they are formed as primordial follicles. The number of follicles in the primordial follicle pool is an important determinant of the reproductive lifespan of a female. Primordial follicles have an oocyte arrested in the diplotene stage of prophase I of meiosis, surrounded by flattened pre-granulosa cells [1,2]. These primordial follicles may stay in their arrested state for months, or even years in long-lived mammals, before undergoing the primordial to primary follicle transition. Once the pool of primordial follicles is depleted, reproduction ceases and women undergo menopause [4,5,6,7]
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