Deprival of testicular innervation induces apoptosis of Leydig cells via caspase-8-dependent signaling: a novel survival pathway revealed.
Leydig cells are the primary source of testosterone in adult males. Recently, a growing body of evidence has shown that testicular innervation functions as a major regulator in Leydig cell steroidogenesis. The question then arises whether this novel regulatory pathway also plays an important role in other biological behaviors of this cell type. In the present study, we selectively resected the superior spermatic nerves (SSNs) or the inferior spermatic nerves (ISNs) to investigate the effects of testicular denervation on survival of Leydig cells. After testicular denervation, Leydig cells displayed morphological characteristics of apoptosis, such as chromatin condensation, cell shrinkage and apoptotic body formation. Flow cytometry combined with TUNEL labeling demonstrated dramatic and persistent apoptosis of Leydig cells in the denervated testes 14 and 21 days after operation. Meanwhile, serum T concentrations in the SSN- or ISN-denervated rats dramatically decreased on day 14 and declined further on day 21. Plasma LH levels underwent a remarkable rise, while serum FSH levels remained unchanged. Immunofluorescent staining and flow cytometry further demonstrated that testicular denervation activated caspase-3 and caspase-8, but not caspase-9 in Leydig cells. Our data indicate that testicular innervation functions as an important survival factor for Leydig cells in vivo.
Gong
Yong-Guang
YG
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an 710016, China. gyg0207@sina.com
Wang
Yi-Qiu
YQ
Gu
Min
M
Feng
Ming-Ming
MM
Zhang
Wei
W
Ge
Ren-Shan
RS
D000818:Animals; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism*; D002470:Cell Survival; D003714:Denervation; D005640:Follicle Stimulating Hormone / Q000097:blood; D007985:Leydig Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013737:Testis / Q000166:cytology / Q000294:innervation*
D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D053181:Caspase 8