A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia  

作　　者：Shin-ichi Tomizawa Kazushige Kuroha Michio Ono Kuniko Nakajima Kazuyuki Ohbo 

机构地区：[1]Department of Histology and Cell Biology,Yokohama City University School of Medicine,Yokohama 236-0004,Japan

出　　处：《Asian Journal of Andrology》2025年第1期37-43,共7页亚洲男性学杂志(英文版)

基　　金：partly supported by Grant-in-Aid for Scientific Research on Innovative Areas funding from the Ministry of Education,Culture,Sports,Science,and Technology(MEXT)KAKENHI(No.22H04677 to KO);a grant from the Japan Society for the Promotion of Science KAKENHI(No.20K09543 to ST,No.20K07228 to KK,and No.19KK0183 to KO);the Takeda Science Foundation(2021 to KK).

摘　　要：Mouse spermatogenesis entails the maintenance and self-renewal of spermatogonial stem cells(SSCs),which require a complex web-like signaling network transduced by various cytokines.Although brain-derived neurotrophic factor(BDNF)is expressed in Sertoli cells in the testis,and its receptor tropomyosin receptor kinase B(TrkB)is expressed in the spermatogonial population containing SSCs,potential functions of BDNF for spermatogenesis have not been uncovered.Here,we generate BDNF conditional knockout mice and find that BDNF is dispensable for in vivo spermatogenesis and fertility.However,in vitro,we reveal that BDNF-deficient germline stem cells(GSCs)exhibit growth potential not only in the absence of glial cell line-derived neurotrophic factor(GDNF),a master regulator for GSC proliferation,but also in the absence of other factors,including epidermal growth factor(EGF),basic fibroblast growth factor(bFGF),and insulin.GSCs grown without these factors are prone to differentiation,yet they maintain expression of promyelocytic leukemia zinc finger(Plzf),an undifferentiated spermatogonial marker.Inhibition of phosphoinositide 3-kinase(PI3K),mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK),and Src pathways all interfere with the growth of BDNF-deficient GSCs.Thus,our findings suggest a role for BDNF in maintaining the undifferentiated state of spermatogonia,particularly in situations where there is a shortage of growth factors.

关 键 词：BDNF SPERMATOGENESIS SPERMATOGONIA stem cells 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]