Hypoxia Inducible Factor 1 Alpha Is Expressed in Germ Cells throughout the Murine Life Cycle

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 (Hif1 alpha) 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 Hif1 alpha was also expressed in the primitive cells of the murine embryo. We observed expression of Hif1 alpha in pre-implantation embryos, specifically the 2-cell stage, morula, and blastocyst. Robust Hif1 alpha expression was also observed in male and female primordial germ cells. We subsequently assessed whether Hif1 alpha was expressed in adult male and female germ cells. In the testis, Hif1 alpha was robustly expressed in spermatogonial cells, in both juvenile (6-week old) and adult (3-month old) males. In the ovaries, Hif1 alpha was expressed in mature oocytes from adult females, as assessed both in situ and in individual oocytes flushed from super-ovulated females. Analysis of Hif1 alpha transcript levels indicates a mechanism of regulation during early development that involves stockpiling of Hif1 alpha 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 Hif1 alpha is expressed throughout the life-cycle, including both the male and female germ line, and point to an important role for Hif1 alpha in early progenitor cells.