Xi Guangyin, An Lei, Jia Zhenwei, Tan Kun, Zhang Jiaxin, Wang Zhuqing, Zhang Chao, Miao Kai, Wu Zhonghong, Tian Jianhui
National Engineering Laboratory for Animal Breeding, College of Animal Sciences and Technology, China Agricultural University, Beijing 100193, China.
National Engineering Laboratory for Animal Breeding, College of Animal Sciences and Technology, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, Inner Mongolia University for the Nationalities, Inner Mongolia 028000, China.
Theriogenology. 2018 Jan 15;106:198-209. doi: 10.1016/j.theriogenology.2017.09.003. Epub 2017 Sep 28.
Meiosis is of prime importance for successful gametogenesis, and insufficient maintenance of oocyte meiotic arrest compromises oocyte developmental competence. Recent studies have demonstrated that the C-type natriuretic peptide (CNP)-Natriuretic peptide receptor 2 (NPR2) pathway can inhibit mammalian oocyte meiotic resumption. In mouse and porcine, the inhibitory effect of mural granulosa cell (MGC)-derived CNP on oocyte meiotic resumption is mediated by NPR2 localized in cumulus cells (CCs) surrounding the oocytes. However, in the present study, we identified a novel mechanism for CNP-induced meiotic arrest that appears to be unique to bovine oocytes. Unlike mouse and porcine, bovine NPR2 not only localizes in CCs, but also in oocyte membranes. We also showed that CNP can directly activate intra-oocyte cGMP production via NPR2 localized in oocyte membranes, in parallel with the CC-mediated pathway. Furthermore, we demonstrated that Npr2 expression in bovine CCs and oocytes were synergistically regulated by estradiol and oocyte-derived growth factors. Finally, based on the profound inhibitory effect of CNP on meiotic resumption, we established a natural factor synchronized in vitro oocyte maturation (NFSOM) system, which can significantly improve the developmental competence of matured oocytes, thereby resulting in higher in vitro embryo production efficiency. Taken together, our study not only provides new insight into understanding the crosstalk between oocytes and follicular somatic cells in mammals, but also presents a promising strategy for improving the in vitro oocyte maturation systems of assisted reproductive technology (ART).
减数分裂对于成功的配子发生至关重要，而卵母细胞减数分裂阻滞维持不足会损害卵母细胞的发育能力。最近的研究表明，C型利钠肽（CNP）-利钠肽受体2（NPR2）途径可抑制哺乳动物卵母细胞减数分裂恢复。在小鼠和猪中，壁颗粒细胞（MGC）衍生的CNP对卵母细胞减数分裂恢复的抑制作用是由定位于卵母细胞周围卵丘细胞（CCs）中的NPR2介导的。然而，在本研究中，我们发现了一种CNP诱导减数分裂阻滞的新机制，这似乎是牛卵母细胞所特有的。与小鼠和猪不同，牛NPR2不仅定位于CCs，还定位于卵母细胞膜。我们还表明，CNP可通过定位于卵母细胞膜中的NPR2直接激活卵母细胞内cGMP的产生，与CC介导的途径并行。此外，我们证明了牛CCs和卵母细胞中Npr2的表达受雌二醇和卵母细胞衍生生长因子的协同调节。最后，基于CNP对减数分裂恢复的显著抑制作用，我们建立了一种自然因子同步体外卵母细胞成熟（NFSOM）系统，该系统可显著提高成熟卵母细胞的发育能力，从而提高体外胚胎生产效率。综上所述，我们的研究不仅为理解哺乳动物卵母细胞与卵泡体细胞之间的相互作用提供了新的见解，也为改进辅助生殖技术（ART）的体外卵母细胞成熟系统提供了一种有前景的策略。
