title: Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury.
abstract: Administration of exogenous epidermal growth factor (EGF) improves testicular injury after acute ischemia-reperfusion (IR) stress, but the molecular basis is poorly understood. The role of endogenous EGF in testicular recovery and the underlying intracellular signaling pathways involved were herein investigated. In mice, testicular IR injury significantly enhanced the expression level of endogenous Egf at the very beginning of reperfusion. Expression of EGF receptor (Egfr (ErbB1)) was accordingly upregulated 3  h after reperfusion. Deprivation of majority of circulated EGF by sialoadenectomy aggravated testicular detriment (especially in pachytene spermatocytes), enhanced germ cell apoptosis, and thereafter resulted in impaired meiotic differentiation after IR insult. Mechanistically, endogenous EGF signaling appeared to be indispensable for the proper maintenance of Sertoli germ cells anchoring junction dynamics during the early testicular recovery. We also provided the in vitro evidences in a well-established rat Sertoli germ cell co-cultures model that the pro-survival effect of endogenous EGF on germ cells in response to testicular IR insult is mediated, at least in part, via the phosphatidylinositol 3-kinase/pAkt pathway. Collectively, our results suggest that the augment of endogenous EGF during the early testicular recovery may act on top of an endocrinous cascade orchestrating the intimate interactions between Sertoli cells and germ cells and may operate as indispensable defensive mechanism in response to testicular IR stress. Future studies in this field would shed light on this complicated pathogenesis.
authors.affiliation: Department of Gynecology and Obstetrics, Reproductive Medicine Center, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Shun
authors.initials: S
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Juan
authors.initials: J
authors.lastname: Qu
authors.forename: Yaning
authors.initials: Y
authors.lastname: Luo
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000502:physiology*; D005260:Female; D005854:Germ Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D051381:Rats; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000503:physiopathology*; D012708:Sertoli Cells / Q000187:drug effects / Q000502:physiology*; D013737:Testis / Q000098:blood supply*; D013997:Time Factors
chemical_list: D004815:Epidermal Growth Factor