Abstract
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is an extracellular matrix metalloproteinase that plays an important role in the process of ovulation. According to previous studies, the expression level of ADAMTS1 in the granulosa cells of polycystic ovarian syndrome (PCOS) patients and the mechanism for regulating oocyte quality and embryonic development potential are still unclear. Our research clarified that ADAMTS1 was significantly increased in granulosa cells of PCOS patients as compared to ovulatory controls. After silencing ADAMTS1 in granulosa cells, cell proliferation and E2 secretion were significantly inhibited, which may be related to the down-regulation of B-cell lymphoma 2 (Bcl2) family genes and key genes involved in E2 synthesis. Through retrospective analysis of the clinical data, it was found that the expression level of ADAMTS1 was significantly positively correlated to the oocyte maturation rate and good-quality embryo rate in PCOS patients. The downregulation of ADAMTS1 in primary granulosa cells lead to the changes in the expression of marker genes for oocyte and embryonic quality. By using immunofluorescence staining, it was found ADAMTS1 was expressed in various stages of pre-implantation embryo but its expression level gradually decreases with the development of the embryo. In addition, the silence of ADAMTS1 in 3PN zygotes significantly prolonged the development time of the zygote to the morula stage. This is, to our knowledge, the first time to explored the mechanism by which ADAMST1 is involved in affecting the quality of oocytes and embryonic development potential, which will provide new evidence for further understanding of the follicular microenvironment and embryo development.
Highlights
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a family of extracellular proteases consisting of 19 mammalian members (Dubail and Apte, 2015)
The estimation of the mRNA (Figure 1A) and protein level (Figure 1B) of ADAMTS1 in the human primary granulosa cells between the two groups revealed that the level of ADAMTS1 was significantly higher in the polycystic ovarian syndrome (PCOS) patients than the ovulatory controls (p < 0.0001)
An immunofluorescence assay was conducted to investigate the expression and localization of ADAMTS1 in granulosa cells, and the results showed that ADAMTS1 was mainly expressed in the cytoplasm of granulosa cells, and the staining intensity of ADAMTS1 in granulosa cells from PCOS patients was stronger as compared with the ovulatory controls (Figure 1C)
Summary
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a family of extracellular proteases consisting of 19 mammalian members (Dubail and Apte, 2015). Previous studies demonstrated that ADAMTS1 participates in the morphogenesis and function maintenance of female reproductive organs through the dynamic shaping of ECM (Shindo et al, 2000) It plays a major role in regulating follicle development and gametogenesis. The knockout of ADAMTS1 in mice limited the expansion of cumulus-oocyte complex (COCs), trapped the oocytes in the follicle wall, and significantly reduced the rates of ovulation and fertilization (Brown et al, 2010) These phenomena could be attributed to the abnormal localization and expression of many key components of ECM, which are the substrates of ADAMTS1. It is speculated that ADAMTS1 is closely related to ovarian function
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