PMID- 31403678 OWN - NLM STAT- MEDLINE DCOM- 20210609 LR - 20211204 IS - 1529-7268 (Electronic) IS - 0006-3363 (Print) IS - 0006-3363 (Linking) VI - 102 IP - 1 DP - 2020 Feb 12 TI - Expression and functional analyses of ephrin type-A receptor 2 in mouse spermatogonial stem cellsdagger. PG - 220-232 LID - 10.1093/biolre/ioz156 [doi] AB - Spermatogonial stem cells (SSCs) undergo continuous self-renewal division in response to self-renewal factors. The present study identified ephrin type-A receptor 2 (EPHA2) on mouse SSCs and showed that supplementation of glial cell-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), which are both SSC self-renewal factors, induced EPHA2 expression in cultured SSCs. Spermatogonial transplantation combined with magnetic-activated cell sorting or fluorescence-activated cell sorting also revealed that EPHA2 was expressed in SSCs. Additionally, ret proto-oncogene (RET) phosphorylation levels decreased following the knockdown (KD) of Epha2 expression via short hairpin ribonucleic acid (RNA). Although the present immunoprecipitation experiments did not reveal an association between RET with EPHA2, RET interacted with FGFR2. The Epha2 KD decreased the proliferation of cultured SSCs and inhibited the binding of cultured SSCs to laminin-coated plates. The Epha2 KD also significantly reduced the colonization of testis cells by spermatogonial transplantation. EPHA2 was also expressed in human GDNF family receptor alpha 1-positive spermatogonia. The present results indicate that SSCs express EPHA2 and suggest that it is a critical modifier of self-renewal signals in SSCs. CI - (c) The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Morimoto, Hiroko AU - Morimoto H AD - Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Kanatsu-Shinohara, Mito AU - Kanatsu-Shinohara M AD - Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. AD - Agency for Medical Research and Development-Core Research for Evolutional Science and Technology, Tokyo, Japan. FAU - Orwig, Kyle E AU - Orwig KE AD - Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. FAU - Shinohara, Takashi AU - Shinohara T AD - Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. LA - eng GR - R01 HD092084/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (RNA, Small Interfering) RN - EC 2.7.10.1 (Receptors, Eph Family) SB - IM MH - Adult Germline Stem Cells/cytology/*metabolism MH - Animals MH - Cell Proliferation/physiology MH - Glial Cell Line-Derived Neurotrophic Factor/metabolism MH - Male MH - Mice MH - Phosphorylation MH - Proto-Oncogene Mas MH - RNA, Small Interfering MH - Receptors, Eph Family/genetics/*metabolism MH - Spermatogonia/cytology/*metabolism MH - Testis/*metabolism PMC - PMC7305687 OTO - NOTNLM OT - Epha2 OT - FGF2 OT - GDNF OT - spermatogenesis OT - spermatogonia EDAT- 2019/08/14 06:00 MHDA- 2021/06/10 06:00 PMCR- 2021/02/12 CRDT- 2019/08/13 06:00 PHST- 2019/04/05 00:00 [received] PHST- 2019/07/06 00:00 [revised] PHST- 2019/08/02 00:00 [accepted] PHST- 2019/08/14 06:00 [pubmed] PHST- 2021/06/10 06:00 [medline] PHST- 2019/08/13 06:00 [entrez] PHST- 2021/02/12 00:00 [pmc-release] AID - 5546742 [pii] AID - ioz156 [pii] AID - 10.1093/biolre/ioz156 [doi] PST - ppublish SO - Biol Reprod. 2020 Feb 12;102(1):220-232. doi: 10.1093/biolre/ioz156.