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

转化生长因子β1(TGFb1)缺失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)的基因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合成受损、植入前胚胎发育受阻和乳腺形态发生障碍有关。本项目的目的是揭示TGFb1基因缺失突变小鼠生殖损伤的机制，并确定外源性全身注射TGFb1在减轻这一损伤中的作用。预计该项目将为TGFb1在调节雄性和雌性生育方面的关键作用提供新的见解，并阐明外源补充TGFb1改善野生动物繁殖性能的前景。这一知识在牲畜养殖业、设计新的避孕疫苗战略、在人类制药行业以及在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.