ESTROGEN RECEPTORS IN MALE REPRODUCTION

男性生殖中的雌激素受体

• 批准号: 6162298
• 负责人: E M EDDY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162298
• 关键词: estrogen receptors; fertility; follicle stimulating hormone; gene mutation; genetically modified animals; hormone regulation /control mechanism; laboratory mouse; luteinizing hormone; male; male reproductive system; reproductive development; testosterone

Summary of Work: The aim of this project is to determine the causes of infertility in male mice with a targeted mutation of the estrogen receptor gene. These studies will also help to define the role of estrogen in male gamete formation and function, and to identify estrogen-regulated genes in the testis and epididymis. The estrogen receptor is a ligand-dependent transcription factor that is essential for regulating female reproductive function, but its role in the male is poorly understood. Our studies found that in adult male estrogen receptor knock-out (ERKO) mice, serum LH and FSH levels were normal, testosterone levels were elevated, and sperm numbers, the percent of sperm that were motile, testis weights, and mating frequencies were reduced. The lumen of the seminiferous tubules were dilated by 20 days of age and began degenerating by 70-90 days of age. The dilation of the tubules may be due to reduced fluid reabsorption in the efferent ducts connecting the testis to the epididymis. Approximately 85% of the fluid leaving the testis is reabsorbed in the efferent ducts by a sodium pump mechanism and the epithelium of these tubules contains higher levels of estrogen receptor than other male reproductive tract tissues. The number and motility of sperm in the epididymis of ERKO mice declined from 8 to 16 weeks of age and the sperm were unable to fertilize eggs in vitro, indicating that infertility was due to altered sperm function, in addition to reduced sperm numbers and mating frequency. This suggests that the estrogen receptor in the male is involved in regulating spermatogenesis, reproductive behavior, and epididymal function. Differential display is being used to identify genes with different levels of expression in the testis and epididymis of juvenile and adult ERKO and wild-type mice. However, changes in gene expression defining the mechanisms that require estrogen action in male reproduction have not yet been identified. Other studies focus on maturation of sperm in the epididymis. As sperm transit the epididymis, they acquire the ability to bind to the zona pellucida of the egg, to display a vigorous and coordinated pattern of flagellar motility, and to undergo capacitation and the acrosome reaction. These processes are being examined in ERKO mice to determine if they are estrogen-regulated and if modifications in these processes are a cause of infertility in ERKO males. Future studies will examine the role of the recently identified estrogen receptor b in these processes.

工作总结： 该项目的目的是确定 雌激素靶向突变的雄性小鼠不育 受体基因 这些研究还将有助于确定 雌激素在雄配子形成和功能中的作用，并确定 睾丸和附睾中的雌激素调节基因。 雌激素 受体是一种配体依赖性转录因子， 调节女性生殖功能，但它在男性中的作用是 不太了解。 我们的研究发现成年男性的雌激素 受体敲除（ERKO）小鼠，血清LH和FSH水平正常， 睾丸激素水平升高，精子数量， 活动精子、睾丸重量和交配频率 降低 生精小管管腔在20 d时扩张 70-90日龄开始退化。 的扩张 小管可能是由于输出管中的液体重吸收减少 连接着睾丸和附睾 大约85%的液体 在输出管中被钠泵重吸收 这些小管的上皮细胞含有更高水平的 雌激素受体比其他男性生殖道组织。 数量 ERKO小鼠附睾中精子的活力从8下降到10。 16周龄，精子无法在体外使卵子受精， 表明不育是由于精子功能改变， 精子数量和交配频率也会减少 这表明 男性体内的雌激素受体参与调节 精子发生、生殖行为和附睾功能。 差异显示被用于鉴定具有不同 青少年和成年人睾丸和附睾中的表达水平 ERKO和野生型小鼠。 然而，基因表达的变化决定了 在男性生殖中需要雌激素作用的机制还没有 尚未被确认。 其他研究集中在精子的成熟， 附睾 当精子通过附睾时，它们获得了 在鸡蛋的透明膜上，显示出一种强烈的， 鞭毛运动的协调模式，并进行获能 和顶体反应。 ERKO正在研究这些过程 小鼠，以确定它们是否受雌激素调节，以及 这些过程是ERKO男性不育的原因。 未来的研究 将研究最近发现的雌激素受体B在 这些过程。