Cellular Determinants of Granulosa Cell Differentiation in Avian Ovarian Follicles

禽类卵巢卵泡颗粒细胞分化的细胞决定因素

• 批准号: 0968784
• 负责人: Alan Johnson
• 金额: $ 37.28万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0968784&HistoricalAwards=false
• 关键词: Cellular; Determinants; Granulosa; Cell; Differentiation

In female vertebrate animals that ovulate a limited number of oocytes (eggs) per ovulation cycle (e.g., mammals, birds, some reptiles), it is the process of ovarian follicle selection that represents the rate-limiting step to fecundity. Follicle selection entails the selective recruitment of one (or more) undifferentiated follicle(s) into the final stages of maturation prior to ovulation, yet the underlying mechanisms of this process are currently undefined in any vertebrate species. Ultimately, the selection mechanism determines the maximum number of offspring that can be produced within any given reproductive cycle. The present studies will test the hypothesis that the inability of undifferentiated follicles to spontaneously undergo follicle selection is normally due to the active suppression of one or more genes (e.g., the Follicle Stimulating Hormone receptor; FSHR) that are required for the differentiation of the follicle's granulosa cell layer. Importantly, it is the granulosa cell layer that nurtures the oocyte throughout follicle development. A second hypothesis to be tested is that at the time of follicle selection there is a switch from a negative regulation of FSHR gene expression to an upregulation of expression. This event is widely assumed to be prerequisite for the maturation of ovarian follicles to the preovulatory stage. The experimental design incorporates cellular and molecular techniques directed at identifying genomic mechanisms by which the expression of genes critical to this selection process in chickens is repressed or enhanced. Results from these studies are predicted to impact our ability to enhance female fertility in endangered species and domesticated food animals, and to better understand select causes of infertility in women. More broadly, the proposed research will serve to provide relevant and cutting-edge training to undergraduate and graduate students (including those from underrepresented populations) whose career goals include teaching and/or research.

在雌性脊椎动物中，每个排卵周期（例如哺乳动物，鸟类，某些爬行动物）排卵的雌性脊椎动物动物，这是卵巢卵泡选择的过程，代表了粪便限制的步骤。卵泡的选择需要在排卵前选择性募集一个（或更多）未分化的卵泡进入成熟的最后阶段，但该过程的基本机制目前在任何脊椎动物物种中都不确定。最终，选择机制决定了可以在任何给定的生殖周期内产生的最大后代数。目前的研究将检验以下假设：通常，由于没有分化的卵泡自发进行卵泡选择的能力通常是由于一个或多个基因（例如，卵泡刺激激素受体； FSHR）的主动抑制是卵泡分化的卵泡颗粒细胞层所需的。重要的是，是颗粒细胞层在整个卵泡发育中培育了卵母细胞。要测试的第二个假设是，在卵泡选择时，从FSHR基因表达的负调节转变为表达的上调。人们普遍认为，这一事件是卵巢卵泡成熟到排卵阶段的先决条件。实验设计结合了针对鉴定基因组机制的细胞和分子技术，通过这些技术，抑制或增强了对鸡在这种选择过程中至关重要的基因的表达。这些研究的结果预计会影响我们在濒危物种和驯养食用动物中增强女性生育能力的能力，并更好地了解女性不孕症的某些原因。更广泛地说，拟议的研究将有助于为本科和研究生（包括来自代表性不足的人群）提供相关和尖端的培训，其职业目标包括教学和/或研究。