Abstract

Pluripotent stem cells of the early embryo, and germ line cells, are essential to ensure uncompromised development to adulthood as well as species propagation, respectively. Recently, the transcription factor hypoxia inducible factor 1 alpha (Hif1α) has been shown to have important roles in embryonic stem cells; in particular, regulation of conversion to glycolytic metabolism and, as we have shown, maintenance of functional levels of telomerase. In the present study, we sought to assess whether Hif1α was also expressed in the primitive cells of the murine embryo. We observed expression of Hif1α in pre-implantation embryos, specifically the 2-cell stage, morula, and blastocyst. Robust Hif1α expression was also observed in male and female primordial germ cells. We subsequently assessed whether Hif1α was expressed in adult male and female germ cells. In the testis, Hif1α was robustly expressed in spermatogonial cells, in both juvenile (6-week old) and adult (3-month old) males. In the ovaries, Hif1α was expressed in mature oocytes from adult females, as assessed both in situ and in individual oocytes flushed from super-ovulated females. Analysis of Hif1α transcript levels indicates a mechanism of regulation during early development that involves stockpiling of Hif1α protein in mature oocytes, presumably to provide protection from hypoxic stress until the gene is re-activated at the blastocyst stage. Together, these observations show that Hif1α is expressed throughout the life-cycle, including both the male and female germ line, and point to an important role for Hif1α in early progenitor cells.

Highlights

  • Hallmark features of the primitive progenitor cells of the early embryo include both pluripotency and an extensive capacity to proliferate

  • Our results show persistent expression of Hif1α in in the early embryo, primordial germ cells (PGCs), and in both male and female adult germ cells, suggesting that Hif1α may be involved in the maintenance of germ stem cells

  • Hif1α is readily detectable in murine embryonic stem cell cultures [27]

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Summary

Introduction

Hallmark features of the primitive progenitor cells of the early embryo include both pluripotency and an extensive capacity to proliferate. The former is attributed to the expression of pluripotency factors, including transcription factors Oct, Klf, Sox and Nanog [1]. The latter is attributed to maintenance of relatively long telomeres by the enzymatic complex telomerase [2]. Much remains to be discovered to allow full elucidation of the cell and molecular mechanisms that regulate the function of these cells.

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