Abstract
The predisposition for the initiation of folliculogenesis in mammals including humans is programmed to start at fetal life and continues until reproductive capacity. The follicles grow from a pool of primordial follicles which retain the major functions in the entire reproductive life of a female. Anti-müllerian hormone (AMH), a glycoprotein belonging to the transforming growth factor-beta family, has an inhibitory effect on ovarian follicle development. The key regulatory target genes in primordial follicle development are of paramount importance in reproductive biology of female. A systems biology method was used to find regulatory genes performing critical role in primordial follicle development. A complete in-depth bioinformatics analysis was performed to investigate the changes in transcriptome of preantral to small antral mouse follicles treated for 12 h and 24 h with two different concentrations; 50 and 200 ng/ml of AMH, and thereby identify candidate genes in time and concentration manner. Firstly, we found differentially expressed genes that were time and concentration dependent in response to AMH. The network analysis of these differentially expressed genes provided new candidate genes and pathways associated with inhibitory action of AMH on the primordial follicle development. To further emphasize the function of AMH, the key identified genes’ protein-protein docking was analyzed and found the intracellular and extracellular protein-protein interaction. This study elucidates one of the novel mechanisms of AMH involvement in inhibition of ovarian follicle development which may lead to prolong productive life in female.
Highlights
The mechanism of activation of primordial follicle to a healthy preantral follicle is of pronounced interest and their interpretation is critical requirement to use the primordial follicle and enhance its efficiency in mammals
differentially expressed www.oncotarget.com genes (DEGs) under a set of defined conditions lead us to the proposition of genes working in network to carry out a certain function, we figured out DEGs to further illustrate its role primordial follicle development. (DEGs list can be found in Supplementary Table 2)
It was clear that the samples in each group were divided into two types (AMH treated and control), which indicating that DEGs in each group had obvious different expression patterns
Summary
The mechanism of activation of primordial follicle to a healthy preantral follicle is of pronounced interest and their interpretation is critical requirement to use the primordial follicle and enhance its efficiency in mammals. The transition of primordial follicle www.oncotarget.com to primary follicle involves the change in the histology of granulosa cells from round to cuboidal epithelial and increase in the oocytes diameter. The transition of primordial pool to primary follicle is regulated by certain paracrine and/or autocrine growth factors. The extracellular hormones/proteins have been investigated and found of critical importance in primordial follicular pool in female reproduction, Anti-müllerian hormone (AMH) performs inhibitory role in follicle transition [8] and chemokine which binds to functionally signaling G-protein-coupled receptors and complete their action [9]. It is reported that oocytes of primordial and primary follicles express stromal derived factor -1 (SDF-1) (chemokine) and when ovaries were cultured with stromal derived factor-1 reveal decrease in follicular diameter as compared with control, suggesting an inhibitory effect of primordial to primary follicle transition [10]
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