title: Slc15a1 is involved in the transport of synthetic F5-peptide into the seminiferous epithelium in adult rat testes.
abstract: Spermiation and BTB restructuring, two critical cellular events that occur across seminiferous epithelium in mammalian testis during spermatogenesis, are tightly coordinated by biologically active peptides released from laminin chains. Our earlier study reported that F5-peptide, synthesized based on a stretch of 50 amino acids within laminin-γ3 domain IV, could reversibly induce the impairment of spermatogenesis, disruption of BTB integrity, and germ cell loss, and thus is a promising male contraceptive. However, how F5-peptide when administered intratesticularly enters seminiferous tubules and exerts effects beyond BTB is currently unknown. Here we demonstrated that Slc15a1, a peptide transporter also known as Pept1, was predominantly present in peritubular myoid cells, interstitial Leydig cells, vascular endothelial cells and germ cells, while absent in Sertoli cells or BTB site. The steady-state protein level of Slc15a1 in adult rat testis was not affected by F5-peptide treatment. Knockdown of Slc15a1 by in vivo RNAi in rat testis was shown to prevent F5-peptide induced disruptive effects on spermatogenesis. This study suggests that Slc15a1 is involved in the transport of synthetic F5-peptide into seminiferous epithelium, and thus Slc15a1 is a novel target in testis that could be genetically modified to improve the bioavailability of F5-peptide as a prospective male contraceptive.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Su
authors.affiliation: Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Population Council, Center for Biomedical Research, New York, NY 10065, USA.
authors.forename: Yan C
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Will M
authors.initials: WM
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, China.
authors.forename: Keping
authors.initials: K
authors.lastname: Ye
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001814:Blood-Testis Barrier / Q000378:metabolism; D003272:Contraceptive Agents, Male / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005854:Germ Cells / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D000074011:Peptide Transporter 1; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology; D027981:Symporters / Q000378:metabolism*
chemical_list: D003272:Contraceptive Agents, Male; D007797:Laminin; D000074011:Peptide Transporter 1; D010455:Peptides; C489940:Slc15a1 protein, rat; D027981:Symporters