Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice

转化生长因子β -1 （TGFb1）零突变小鼠生殖损伤的机制基础。编码细胞因子转化生长因子β -1 （TGFb1）基因的零突变导致雄性和雌性小鼠不育。在最近的实验中，我们发现TGFb1缺乏与卵巢和睾丸类固醇生成受损、着床前胚胎发育受阻和乳腺形态发生中断有关。当前项目的目的是揭示TGFb1零突变小鼠生殖损伤的机制基础，并确定外源性全身递送TGFb1在减轻这种损伤中的作用。预计该项目将为TGFb1在控制雄性和雌性生殖能力中的关键作用提供新的见解，并为外源补充TGFb1以提高野生型动物的生殖性能提供前景。这种知识在牲畜养殖业、设计新的避孕疫苗战略、人类制药工业和设计新的避孕疫苗战略方面具有潜在的重要应用。

Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to unravel the mechanistic basis of the reproductive lesion in TGFb1 null mutant mice and to determine the effect of exogenous systemic delivery of TGFb1 in alleviating this lesion. It is expected that the project will provide new insight into key roles for TGFb1 in governing male and female fertility, and shed light on the prospects for exogenous supplementation of TGFb1 for improving reproductive performance in wild-type animals. This knowledge has potentially important applications in the livestock breeding industry, in devising novel contraceptive vaccine strategies, in the human pharmaceutical industry, and in devising novel contraceptive vaccine strategies.