Proteomic analysis of testis biopsies in men treated with transient scrotal hyperthermia reveals the potential targets for contraceptive development.
Mild testicular heating safely and reversibly suppresses spermatogenesis. In this study, we attempted to clarify the underlying molecular mechanism(s) involved in heat-induced spermatogenesis suppression in human testis. We conducted global proteomic analyses of human testicular biopsies before, and at 2 and 9 wk after heat treatment. Thirty-one and Twenty-six known proteins were identified with significant differential expression at 2 and 9 wk after heat treatment, respectively. These were used to characterize the cellular and molecular events in the testes when seminiferous epithelia became damaged (2 wk) and recovered (9 wk). At 2 wk post-treatment, the changed expression of a series of proteins could promote apoptosis or suppress proliferation and cell survival. At 9 wk post-treatment, the changed expression of proteins mainly promoted cell proliferation, differentiation and survival, but resisted cell apoptosis. Among those heat-regulated proteins, HNRNPH1 was selected for the further functional study. We found that HNRNPH1 was an anti-apoptosis protein that could regulate the expression of other heat-induced proteins. In conclusion, heat-induced reversible suppression of spermatogenesis occurred by modulating the expression of proteins related to proliferation, differentiation, apoptosis and cell survival pathways. These differentially expressed proteins were found to be key molecular targets affecting spermatogenesis after heat treatment.
Zhu
Hui
H
Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, P. R. China.
Cui
Yugui
Y
Xie
Jin
J
Chen
Ling
L
Chen
Xiangxiang
X
Guo
Xuejiang
X
Zhu
Yefei
Y
Wang
Xinghai
X
Tong
Jiansun
J
Zhou
Zuomin
Z
Jia
Yue
Y
Lue
Yan-He
YH
Hikim
Amiya Sinha
AS
Wang
Christina
C
Swerdloff
Ronald S
RS
Sha
Jiahao
J
D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D002460:Cell Line; D005786:Gene Expression Regulation; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism*
D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D020543:Proteome; D034741:RNA, Small Interfering