br Introduction Anti Mullerian hormone AMH

Introduction Anti-Mullerian hormone (AMH), also called Mullerian-inhibiting substance (MIS), is a member of the TGF-β superfamily and is well known for its role in Mullerian duct regression during male sexual differentiation [1]. In females, AMH is mainly expressed in the granulosa football (GCs) of preantral and small antral follicles [[2], [3], [4], [5]], and AMH has been shown to inhibit the recruitment of primordial follicles. The expression levels of AMH vary during the different developmental stages of follicles. AMH expression begins in primary follicles and reaches a maximal level in small antral follicles [6]. Reports have shown that the serum/plasma AMH level can be a reliable marker of ovarian reserves and the ovarian response to gonadotropin-based stimulatory treatments in humans, bovines and goats [[7], [8], [9], [10]]. The regulation of AMH expression in follicles remains poorly understood. Several factors may affect the expression of AMH. For example, Joelle Taieb et al. [11] recently determined that AMH transcription in granulosa cells is enhanced by the FSH- and cAMP-mediated activation of the AMH promoter through protein kinase A (PKA)/p38-dependent signaling pathways. In addition, a stimulating effect of the bone morphogenetic proteins (BMPs) on AMH expression has been proven in human, hen, bovine, and ovine GCs in vitro [[12], [13], [14], [15], [16]]. Because of the importance of the BMP system in regulating the reproductive process, additional studies have focused on the mechanism underlying the contribution of BMPs to ovarian function. BMPs also belong to the TGF-β superfamily and play important roles as autocrine and/or paracrine factors in regulating the development of follicles [17]. In particular, BMP15, which is produced by oocytes, has been shown to be involved in the regulation of follicular [18,19] and cumulus cell function [[20], [21], [22], [23]], and BMP15 is found in the oocytes of all types of follicles and in the GCs from primary follicles onward [24]. In addition, BMP15 mutations are related to reproductive activity. As components of the TGF-β superfamily, small mothers against decapentaplegic (SMAD) proteins, when phosphorylated, have been found to be related to BMP function [17]. Studies have shown that BMP15 and BMP4 activate the SMAD1/5/8 signaling pathway by inducing the phosphorylation of the SMAD proteins, which are then transferred to the nucleus to activate the transcription of target genes [26,27]. Recently, several reports have shown that BMPs may regulate AMH via the SMAD signaling pathway [16,25]. The p38 MAPK protein is expressed in oocytes and GCs and regulates oocyte maturation and fertilization [28]. And the phosphorylation of the p38 MAPK pathway plays an important role in the regulation of follicular growth and development. It has been found that the second messenger cAMP of LH and FSH can stimulate the transcription of AMH, and some of the genes involved in this process pass through the p38 MAPK pathway to impact the promoter region of AMH. This suggests that BMP15 may also affect the expression of AMH through the p38 MAPK pathway. Therefore, we hypothesized in this research that BMP15 can regulate AMH expression via the p38 MAPK pathway. If this hypothesis is true, AMH expression in goat GCs will change when the goat GCs are treated with an inhibitor of p38 MAPK and an siRNA specific for p38 MAPK in vitro.
Materials and methods
Results
Discussion Taieb et al. [11] showed that gonadotropins and cAMP could stimulate AMH transcription by activating the AMH promoter through protein kinase A (PKA)/p38-dependent signaling pathways in human GCs. Our study found that BMP15 enhanced the transcription and secretion of AMH and that an inhibitor of p38 MAPK significantly reduced the expression of AMH. Thus, it was shown that the p38 MAPK signaling pathway affected BMP15-induced AMH expression.