BMP15 blocking peptide

In addition to somatic cell-derived growth factors, oocyte-derived growth differentiation factor (GDF)9 and bone morphogenetic protein (BMP) 15 play essential roles in female fertility. However, few studies have investigated their effects on human ovarian steroidogenesis, and fewer still have examined their differential effects or underlying molecular determinants. In the present study, we used immortalized human granulosa cells (SVOG) and human granulosa cell tumor cells (KGN) to compare the effects of GDF9 and BMP15 on steroidogenic enzyme expression and investigate potential mechanisms of action. In SVOG cells, neither GDF9 nor BMP15 affects the mRNA levels of P450 side-chain cleavage enzyme or 3 beta-hydroxysteroid dehydrogenase. However, treatment with BMP15, but not GDF9, significantly decreases steroidogenic acute regulatory protein (StAR) mRNA and protein levels as well as progesterone production. These suppressive effects, along with the induction of Sma and Mad-related protein (SMAD) 1/5/8 phosphorylation, are attenuated by cotreatment with 2 different BMP type I receptor inhibitors (dorsomorphin and DMH-1). Furthermore, depletion of activin receptor-like kinase (ALK)3 using small interfering RNA reverses the effects of BMP 15 on SMAD1/5/8 phosphorylation and StAR expression. Similarly, knockdown of ALK3 abolishes BMP15-induced SMAD1/5/8 phosphorylation in KGN cells. These results provide evidence that oocyte-derived BMP15 down-regulates StAR expression and decreases progesterone production in human granulosa cells, likely via ALK3-mediated SMAD1/5/8 signaling. Our findings suggest that oocyte may play a critical role in the regulation of progesterone to prevent premature luteinization during the late stage of follicle development.

Ovary development is a complex process involving numerous genes; the molecular mechanism underlying the ovary development of carp is still unknown. Here we used Illumina HiSeg (TM) 2500 to explore the transcriptome of undifferentiated gland (PG), juvenile ovary (OJ) and adult ovary (OA) of Yellow River carp (Cyprinus carpio). A total of 58,749 unigenes were obtained, comprising 45,707 known genes and 13,042 new genes. We identified differentially-expressed genes (DEGs) during development and characterized the functional properties of DEGs by comparison with the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes databases. qRT-PCR was used to analyze the expression of 22 DEGs and the results corresponded with those of RNA-Seq. Among DEGs between PG and OJ, some upstream regulators of gonad development were upregulated in PG, such as cypi9a and sox9, while some oocytespecific genes were upregulated in OJ, such as nobox, bmp15 and zp2. Among DEGs between OJ and OA, many oocyte physiological function-related genes were upregulated in OA, such as fern-1 and foxl2. GO analysis showed a higher number of DEGs from PG OJ analysis were assigned to reproduction terms. Furthermore, our investigation has also revealed DEGs identified from PG OJ analysis were enriched in several important functional pathways, such as Fanconi anemia and the notch signal pathway. These data suggested a dynamic shift in gene expression during ovary development, and DEGs between PG and OJ provided crucial candidate gene data for the study of ovarian differentiation. Additionally, a total of 1,776,769 single nucleotide polymorphisms and 157,279 INDEs were revealed from transcriptome data. This result will contribute to knowledge of ovary differentiation of Yellow River carp. (C) 2017 Elsevier Inc. All rights reserved.