Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis

Gaurav Tyagi; Kay Carnes; Carla Morrow; Natalia V Kostereva; Gail C Ekman; Daryl D Meling; Chris Hostetler; Michael Griswold; Kenneth M Murphy; Rex A Hess; Marie-Claude Hofmann; Paul S Cooke

doi:10.1095/biolreprod.108.075200

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Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis

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Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis

Gaurav Tyagi, Kay Carnes, Carla Morrow, Natalia V Kostereva, Gail C Ekman, Daryl D Meling, Chris Hostetler, Michael Griswold, Kenneth M Murphy, Rex A Hess, …

Biology of reproduction, Vol.81(2), pp.258-266

08/2009

DOI: https://doi.org/10.1095/biolreprod.108.075200

Handle:

https://hdl.handle.net/2376/104128

PMID: 19369650

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Abstract

Immunohistochemistry

Proto-Oncogene Proteins c-ret - metabolism

Testis - metabolism

Cell Proliferation

Spermatogenesis - genetics

Germ Cells - transplantation

Microdissection

Transcription Factors - deficiency

Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism

Male

RNA, Messenger - metabolism

Recombinant Fusion Proteins - metabolism

DNA-Binding Proteins - deficiency

Spermatogonia - metabolism

DNA-Binding Proteins - metabolism

Testis - embryology

Gene Expression Regulation, Developmental

Sertoli Cells - cytology

Fibroblast Growth Factor 2 - metabolism

Germ Cells - cytology

Germ Cells - metabolism

Spermatogonia - cytology

Recombinant Fusion Proteins - administration & dosage

Animals, Newborn

Sertoli Cells - metabolism

Cells, Cultured

Transcription Factors - genetics

DNA-Binding Proteins - genetics

Fibroblast Growth Factor 2 - administration & dosage

Testis - growth & development

Glial Cell Line-Derived Neurotrophic Factor - administration & dosage

Glial Cell Line-Derived Neurotrophic Factor Receptors - genetics

Mice, Knockout

Transcription Factors - metabolism

Animals

Glial Cell Line-Derived Neurotrophic Factor Receptors - administration & dosage

Mice

Proto-Oncogene Proteins c-ret - genetics

Mice that are ets variant gene 5 (ETV5) null (Etv5(-/-)) undergo the first wave of spermatogenesis but lose all spermatogonial stem cells (SSCs) during this time. The SSC loss in Etv5(-/-) mice begins during the neonatal period, suggesting a role for ETV5 in SSC self-renewal during this period. Herein, we show that Etv5 mRNA was present in perinatal mouse testis and that ETV5 was expressed in fetal Sertoli cells and by germ cells and Sertoli cells during the neonatal period. Transplantation of Etv5(-/-) germ cells failed to establish spermatogenesis in W/W(v) mice testes, indicating that germ cell ETV5 has a key role in establishment or self-renewal of transplanted SSCs. The SSC self-renewal is stimulated by glial cell-derived neurotrophic factor (GDNF) acting through the RET/GDNF family receptor alpha 1 (GFRA1) receptor complex in SSCs. Immunohistochemistry, quantitative PCR, and laser capture microdissection revealed decreased RET mRNA and protein expression in spermatogonia of neonatal Etv5(-/-) mice by Postnatal Days 4-8, indicating that disrupted GDNF/RET/GFRA1 signaling may occur before initial spermatogonial stem/progenitor cell decrease. Etv5(-/-) spermatogonia had reduced proliferation in vivo and in vitro. Decreased cell proliferation may cause the observed decreases in the number of type A spermatogonia (Postnatal Day 17) and daily sperm production (Postnatal Day 30) in Etv5(-/-) mice, indicating quantitative impairments in the first wave of spermatogenesis. In conclusion, ETV5 is expressed beginning in fetal Sertoli cells and can potentially have effects on neonatal Sertoli cells and germ cells. In addition, ETV5 has critical effects on neonatal spermatogonial proliferation, which may involve impaired signaling through the RET receptor.

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Title: Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis
Creators: Gaurav Tyagi - Department of Veterinary Biosciences and Pathobiology, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
Kay Carnes
Carla Morrow
Natalia V Kostereva
Gail C Ekman
Daryl D Meling
Chris Hostetler
Michael Griswold
Kenneth M Murphy
Rex A Hess
Marie-Claude Hofmann
Paul S Cooke
Publication Details: Biology of reproduction, Vol.81(2), pp.258-266
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: T32 ES007326 / NIEHS NIH HHS HD44543 / NICHD NIH HHS Howard Hughes Medical Institute R01 HD044543 / NICHD NIH HHS K02 HD054607 / NICHD NIH HHS C06 RR016515 / NCRR NIH HHS C06RR16515 / NCRR NIH HHS
Identifiers: 99900547092201842
Language: English
Resource Type: Journal article