The control of estradiol and progesterone secretion by TGF-beta in bovine ovarian follicles

TGF-β对牛卵泡雌二醇和孕激素分泌的控制

• 批准号: 89678-2006
• 负责人: Carrière, Paul
• 金额: $ 1.74万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=363678
• 关键词: control; estradiol; progesterone; secretion; TGF

One of the major limiting factors in the production of embryos from cattle of high genetic merit is the variable number of recruited follicles following a standard superovulatory hormone treatment resulting in poor ovulation rates. A better understanding of the role of locally produced and circulating hormones in normal ovarian follicle development is necessary to resolve this problem. In cattle, antral follicle development from 1 to 4 mm is dependent on the action of pituitary hormones (FSH,LH); metabolic factors (IGF, insulin); and locally produced ovarian growth factors of the TGF-ß superfamily. These factors must be present to stimulate the production of estradiol which is a key hormone involved in follicle growth.  Once the follicles have reached the 4 mm threshold, they embark in a fast-growth phase lasting 5-6 days where selection of a single dominant ovulatory follicle occurs. We have shown that TGF-ß1 has multifunctional effects and can either stimulate or inhibit estradiol production by granulosa cells of the developing follicle. The objective of this research program is to understand if and how TGF-ß1 can act as a survival factor that limits proliferation and slows down follicle growth while maintaining the granulosa cell viable, and how TGF-B1 inhibits FSH-induced production of estradiol and progesterone. This will be achieved using molecular biology techniques with an in vitro model of cultured bovine granulosa cells. A better understanding of the role of TGF-ß1 and related molecules will be important to increase the pool of follicles that can respond to FSH in order to improve superovulatory response. This research is also relevant to find new ways to prevent and correct infertility problems associated with ovarian inactivity.

从具有高遗传价值的牛生产胚胎的主要限制因素之一是在标准超排卵激素治疗后募集的卵泡数量可变，导致排卵率低。更好地了解局部产生和循环激素在正常卵泡发育中的作用对解决这个问题是必要的。在牛中，1至4 mm的窦卵泡发育取决于垂体激素（FSH、LH）、代谢因子（IGF、胰岛素）和TGF-β超家族局部产生的卵巢生长因子的作用。这些因素必须存在以刺激雌二醇的产生，雌二醇是参与卵泡生长的关键激素。一旦卵泡达到4 mm阈值，它们就进入持续5-6天的快速生长期，在此期间发生选择单个优势排卵卵泡。我们已经证明TGF-β 1具有多功能作用，可以刺激或抑制发育卵泡的颗粒细胞产生雌二醇。本研究计划的目的是了解TGF-β 1是否以及如何作为一种生存因子，限制增殖和减缓卵泡生长，同时保持颗粒细胞的活力，以及TGF-β 1如何抑制FSH诱导的雌二醇和孕酮的产生。这将使用分子生物学技术和培养的牛颗粒细胞体外模型来实现。更好地理解TGF-β 1和相关分子的作用对于增加能够对FSH反应的卵泡池以改善超排卵反应将是重要的。这项研究也有助于找到新的方法来预防和纠正与卵巢不活动相关的不孕问题。