Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.
Mice lacking TYRO3, 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 TYRO3. 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.
Chen
Yongmei
Y
Department of Cell Biology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, People's Republic of China.
Wang
Huizhen
H
Qi
Nan
N
Wu
Hui
H
Xiong
Weipeng
W
Ma
Jing
J
Lu
Qingxian
Q
Han
Daishu
D
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D012708:Sertoli Cells / Q000378:metabolism / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology; D013094:Spermatozoa / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase
D011518:Proto-Oncogene Proteins; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; C513478:Tyro3 protein, mouse; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; C000722290:AXL receptor tyrosine kinase, mouse