De Cesaro Matheus P, de Macedo Mariana P, da Rosa Paulo R A, Dos Santos Joabel T, Mea Ricardo D, da Nóbrega Janduí E, Duggavathi Raj, Gasperin Bernardo G, Gonçalves Paulo Bayard D, Bordignon Vilceu
Reproduction. 2024 Dec 9;169(1). doi: 10.1530/REP-24-0187. Print 2025 Jan 1.
The natriuretic peptide system, particularly the C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (NPR2), plays a critical role in regulating mammalian ovarian functions, including oocyte-cumulus cell communication and meiotic maturation. However, the contribution of natriuretic peptide receptor 3 (NPR3) to these processes has not been thoroughly investigated. Data from this study provide compelling evidence that NPR3 is involved in modulating gonadotropin signaling and regulating cumulus cell expansion in cattle.
The significant role of CNP and its receptor 2 (NPR2) in regulating oocyte meiotic maturation and facilitating communication between oocytes and surrounding cumulus cells has been well documented in various mammalian species including mice, cattle and swine. However, further investigation is needed to ascertain whether natriuretic peptide receptors (NPRs) are involved in regulating other essential ovarian functions. Hence, this study aimed to explore the potential involvement of NPRs in the regulation of cumulus expansion and oocyte meiotic maturation in bovine cumulus-oocyte complexes (COCs). The findings revealed that NPR3 mRNA abundance was downregulated by follicle-stimulating hormone and luteinizing hormone in cumulus cells of bovine COCs during in vitro maturation (IVM), while NPR2 mRNA levels were not affected by gonadotropins. Inhibition of the epidermal growth factor receptor (EGFR) during IVM of COCs prevented the NPR3 mRNA downregulation induced by gonadotropins in cumulus cells. Additionally, treatment of COCs during IVM with an NPR3 agonist (cANP4-23) inhibited cumulus expansion induced by gonadotropins. This inhibitory effect was further intensified when COCs were cotreated with cANP4-23 and CNP. These findings provide robust evidence indicating that normal cumulus expansion in bovine COCs involves an inhibitory effect of gonadotropins on NPR3 mRNA expression, which is mediated via EGFR signaling. The study also provides evidence that CNP and NPR3 interact synergistically to regulate cumulus expansion in response to gonadotropins.
利钠肽系统，尤其是C型利钠肽（CNP）和利钠肽受体2（NPR2），在调节哺乳动物卵巢功能中起关键作用，包括卵母细胞-卵丘细胞通讯和减数分裂成熟。然而，利钠肽受体3（NPR3）对这些过程的贡献尚未得到充分研究。本研究的数据提供了令人信服的证据，表明NPR3参与调节牛的促性腺激素信号传导和卵丘细胞扩展。
CNP及其受体2（NPR2）在调节卵母细胞减数分裂成熟以及促进卵母细胞与周围卵丘细胞之间通讯方面的重要作用，已在包括小鼠、牛和猪在内的各种哺乳动物物种中得到充分证明。然而，需要进一步研究以确定利钠肽受体（NPRs）是否参与调节其他重要的卵巢功能。因此，本研究旨在探讨NPRs在调节牛卵丘-卵母细胞复合体（COCs）中卵丘扩展和卵母细胞减数分裂成熟方面的潜在作用。研究结果显示，在体外成熟（IVM）过程中，牛COCs卵丘细胞中的NPR3 mRNA丰度受到促卵泡激素和促黄体生成素的下调，而NPR2 mRNA水平不受促性腺激素影响。在COCs的IVM过程中抑制表皮生长因子受体（EGFR）可防止促性腺激素诱导的卵丘细胞中NPR3 mRNA下调。此外，在IVM期间用NPR3激动剂（cANP4-23）处理COCs可抑制促性腺激素诱导的卵丘扩展。当COCs与cANP4-23和CNP共同处理时，这种抑制作用进一步增强。这些发现提供了有力证据，表明牛COCs中正常的卵丘扩展涉及促性腺激素对NPR3 mRNA表达的抑制作用，这是通过EGFR信号传导介导的。该研究还提供证据表明，CNP和NPR3协同相互作用以调节对促性腺激素的卵丘扩展反应。
