PDF(Pubmed)
Abstract：
The ovarian follicle is a complex structure that protects and helps in the maturation of the oocyte, and then releases it through the controlled molecular and structural remodeling process of ovulation. The progesterone receptor (PGR) has been shown to be essential in regulating ovulation-related gene expression changes. In this study, we found disrupted expression of the cellular adhesion receptor gene Sema7A in the granulosa cells of PGR-/- mice during ovulation. We subsequently found that expression of Sema7A in preovulatory follicles is promoted by gonadotropins and hypoxia, establishing an asymmetrical pattern with the SEMA7A protein enriched at the apex of large antral follicles. Sema7A expression was downregulated through a PGR-dependent mechanism in the periovulatory period, the abundance of SEMA7A protein was reduced, and the asymmetric pattern became more homogeneous after an ovulatory stimulus. Receptors for Sema7A can either repel or promote intercellular adhesion. During ovulation, striking inverse regulation of repulsive Plxnc1 and adhesive Itga5/Itgb1 receptors likely contributes to dramatic tissue remodeling. The adhesive receptor Itga5 was significantly increased in periovulatory granulosa cells and cumulus-oocyte complexes (COCs), and functional assays showed that periovulatory granulosa cells and COCs acquire increased adhesive phenotypes, while Sema7A repels granulosa cell contact. These findings suggest that the regulation of Sema7A and its associated receptors, along with the modulation of integrin α5, may be critical in establishing the multilaminar ovarian follicle structure and facilitating the remodeling and apical release of the cumulus-oocyte complex during ovulation.
摘要：
卵泡是一个复杂的结构，可以保护和帮助卵母细胞的成熟，然后通过受控的排卵分子和结构重塑过程释放它。孕激素受体（PGR）已被证明在调节排卵相关基因表达变化中至关重要。在这项研究中,我们发现排卵过程中PGR-/-小鼠颗粒细胞中细胞粘附受体基因Sema7A的表达被破坏。我们随后发现，促性腺激素和缺氧促进了Sema7A在排卵前卵泡中的表达，建立一个不对称的模式与SEMA7A蛋白富集在大腔卵泡的顶点。Sema7A表达在排卵期通过PGR依赖性机制下调，SEMA7A蛋白的丰度降低，不对称模式在排卵刺激后变得更加均匀。Sema7A的受体可以排斥或促进细胞间粘附。在排卵期间,排斥性Plxnc1和粘附性Itga5/Itgb1受体的惊人反向调节可能有助于剧烈的组织重塑。在排卵周期颗粒细胞和卵丘-卵母细胞复合物（COCs）中，粘附受体Itga5显着增加，和功能测定表明，围排卵颗粒细胞和COCs获得增加的粘附表型，而Sema7A排斥颗粒细胞接触。这些发现表明，Sema7A及其相关受体的调节，与整合素α5的调节一起，可能对于建立多层卵泡结构以及促进排卵过程中卵丘-卵母细胞复合物的重塑和顶端释放至关重要。
