EPAS1 is required for spermatogenesis in the postnatal mouse testis

Michaela Gruber, Lijoy K. Mathew, Anja C. Runge, Joseph A. Garcia, M. Celeste Simon

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Spermatogenesis, a process involving the differentiation of spermatogonial stem cells into mature spermatozoa, takes place throughout masculine life. A complex system in the testis, including endocrine signaling, physical interactions between germ and somatic cells, spermatocyte meiosis, and timely release of spermatozoa, controls this cycle. We demonstrate herein that decreased O2 levels and Epas1 activation are critical components of spermatogenesis. Postnatal Epas1 ablation leads to male infertility, with reduced testis size and weight. While immature spermatogonia and spermatocytes are present in Epas1Delta/Delta testes, spermatid and spermatozoan numbers are dramatically reduced. This is not due to germ cell-intrinsic defects. Rather, EpasDelta/Delta Sertoli cells exhibit decreased ability to form tight junctions, thereby disrupting the blood-testis barrier necessary for proper spermatogenesis. Reduced numbers of tight junction complexes are due to decreased expression of multiple genes encoding tight junction proteins, including TJP1 (ZO1), TJP2 (ZO2), and occludin. Furthermore, Epas1Delta/Delta testes exhibit disrupted basement membranes surrounding the seminiferous tubules, causing the premature release of incompletely differentiated germ cells. We conclude that low O2 levels in the male gonad regulate germ cell homeostasis in this organ via EPAS1.

Original languageEnglish (US)
Pages (from-to)1227-1236
Number of pages10
JournalBiology of reproduction
Issue number6
StatePublished - Jun 2010


  • Developmental biology
  • Hypoxia
  • Sertoli cells
  • Signal transduction
  • Sperm
  • Spermatogenesis
  • Testis
  • Tight junctions

ASJC Scopus subject areas

  • Reproductive Medicine


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