Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice
Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice
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DOI：
10.1530/rep-09-0101
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发表时间：
2009-10-01
期刊：
影响因子：
3.8
通讯作者：
Han, Daishu
中科院分区：
文献类型：
--
作者：
Chen, Yongmei;Wang, Huizhen;Han, Daishu
缺乏TYR03、AXL和MER （TAM）受体酪氨酸激酶（RTKs）的小鼠雄性不育。TAM RTKs调节男性生育能力的机制尚不清楚。在这项研究中，我们更详细地分析了TAM三突变体（TAM(-/-)）小鼠的睾丸表型，试图了解其机制。我们发现三个TAM RTKs协同调节男性生育能力，MER似乎比AXL和TYR03更重要。TAM（-/-）睾丸显示生殖细胞从细长的精细胞逐渐丧失到精原细胞。年轻成年TAM（-/-）小鼠表现出少弱畸形精子症和精子细胞的各种形态畸形。随着小鼠年龄的增长，生殖细胞最终从精管中消失。此外，我们发现与野生型对照相比，TAM（-/-）支持细胞具有受损的吞噬活性和大量差异表达基因。相比之下，间质细胞的功能不受TAM RTKs突变的明显影响。因此，我们得出结论，支持细胞的次优功能导致TAM（-/-）小鼠精子发生受损。这些结果为TAM rtk调控男性生育能力的机制提供了新的见解。复制（2009）138 655-666
Mice lacking TYR03, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYR03. TAM(-/-) testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-) mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-) Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility. Reproduction (2009) 138 655-666