Cell signaling in ovarian function

细胞是生命的单位。细胞作为单个实体或群体的一部分发挥作用。细胞对其环境的适当反应非常重要，不仅对于细胞的生存，而且对于发挥生理作用也非常重要。细胞对激素刺激的反应涉及信号转导，其中通常包括作为关键参与者的环核苷酸。近几十年来，环磷酸腺苷 (cAMP) 的研究比环磷酸鸟苷 (cGMP) 多得多。在卵巢中，cAMP 的作用已被描述为对卵泡刺激素 (FSH)、黄体生成素 (LH) 的反应，并在类固醇生成中进行了研究，但是 cGMP 在卵巢卵泡细胞中的作用又如何呢？在过去的几年中，由于哺乳动物卵母细胞减数分裂恢复的抑制模型，cGMP 的贡献受到了越来越多的关注。该模型表明，cGMP 主要由颗粒细胞和卵丘细胞响应 C 型利尿钠肽而合成。颗粒细胞、卵丘细胞和卵母细胞之间通过间隙连接产生的电生理合胞体允许cGMP从颗粒细胞扩散到卵母细胞，从而抑制卵母细胞磷酸二酯酶。这种酶抑制作用会增加卵母细胞内的 cAMP，从而阻止减数分裂的恢复。然而，人们对 cGMP 在卵泡中的作用知之甚少。 cGMP 不太可能只是等待转移到卵母细胞。 cGMP 的目标是什么？ cGMP 的生理影响有哪些？ cGMP 是否调节 cAMP 反应？拟议研究计划的长期目标是加深我们对信号转导在卵泡不同生理反应中重要性的理解。由于 cAMP 介导 FSH 和 LH 反应，例如细胞分化，因此假设 cGMP 作为第二信使发挥着主要的生理作用，可能调节电生理合胞体的细胞分化。因此，除了cGMP在抑制卵母细胞减数分裂恢复中的作用外，它在卵泡细胞内的生理贡献是什么？短期目标是 1) 通过比较三个卵泡阶段来表征 cGMP 信号传导涉及的分子机制； 2) 通过研究磷酸化蛋白质组来识别cGMP靶点； 3) 使用化学激动剂和抑制剂证明 cGMP 在调节卵巢功能中的生理作用。该研究项目对当前有关在体外成熟过程中提高卵母细胞质量的知识做出了重大贡献。这将影响与雌配子质量相关的新生殖生物技术的发展，并导致猪肉行业寻求的遗传改良。最后，该研究项目评估了基本信号传导，这对于奶牛等其他物种也有有益的应用。

The cell is the unit of life. A cell functions as a single entity or as part of a group. The appropriate response of a cell to its environment is of great importance, not only for cell's survival, but for performing a physiological role. The cell's response to hormonal stimulation involves signal transduction which often includes cyclic nucleotides as key players. In recent decades, cyclic adenosine monophosphate (cAMP) has become much more studied than cyclic guanosine monophosphate (cGMP). In the ovary, the contribution of cAMP has been characterized in response to follicle-stimulating hormone (FSH), luteinizing hormone (LH), and studied in steroidogenesis, but what about the role of cGMP in the cells of ovarian follicles? Over the past few years, the contribution of cGMP has gained more attention because of the inhibitory model of oocyte meiotic resumption in mammals. This model suggests that the cGMP is synthesized mainly by the granulosa and cumulus cells in response to the C-type natriuretic peptide. The electrophysiological syncytium created between granulosa cells, cumulus cells and the oocyte by gap junctions allows cGMP to diffuse from the granulosa cells to the oocyte, and consequently inhibits oocyte phosphodiesterase. This enzymatic inhibition increases intra-oocyte cAMP that blocks meiotic resumption. However, very little is known about the role of cGMP in ovarian follicles. It is unlikely that cGMP is only waiting to move to the oocyte. What does cGMP target? What are the physiological impacts of cGMP? Does cGMP modulate cAMP response? The long-term objective of the proposed research program is to refine our understanding of the importance of signal transduction in the different physiological responses of the ovarian follicles. Since cAMP mediates FSH and LH responses such as cellular differentiation, the hypothesis is that cGMP plays a major physiological role as a second messenger, possibly modulating the cellular differentiation of the electrophysiological syncytium. Therefore, aside from the role of cGMP in the inhibition of oocyte meiotic resumption, what is its physiological contribution within the cells of the ovarian follicle? The short-term objectives are to 1) characterize the molecular machinery involved in cGMP signaling by comparing three follicular stages; 2) to identify cGMP targets by studying the phosphoproteome; and 3) to demonstrate the physiological involvement of cGMP in mediating ovarian functions using chemical agonists and inhibitors. This research program represents a major contribution to the current knowledge about improving oocyte quality during in-vitro maturation. This will impact the development of new reproductive biotechnology related to the quality of the female gamete, as well as lead to genetic improvements sought after by the pork industry. Finally, this research program assesses fundamental signaling which also has beneficial applications to other species such as dairy cattle.