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

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.

Reduced Glycolysis Contributed to Inhibition of Testis Spermatogenesis in Rats After Chronic Methamphetamine Exposure

“…HIF1α is closely related to oxidative stress [15] and regulates the glycolysis involved in testicular spermatogenesis [16]. GLUT1 is a transmembrane protein involved in the regulation of cellular glucose metabolism in the testis, which is also regulated by HIF1α [17].…”

HYPOXIA AND REPRODUCTIVE HEALTH: Hypoxia and ovarian function: follicle development, ovulation, oocyte maturation

“…An evaluation of HIF1A protein indicates its presence in granulosa cells of numerous animal models: mouse (Kim et al 2009), rat (Zhang et al 2015), bovine (Berisha et al 2017), porcine (Boonyaprakob et al 2005) and human (Herr et al 2004, Henríquez et al 2017. Furthermore, HIF1A is expressed in mature mouse oocytes and continues to be expressed after fertilisation, from the 2-cell to blastocyst stage (Takahashi et al 2016).…”

Regulation of primordial follicle formation, dormancy, and activation in mice

“…In the female germline, HIF1 is expressed in all stages of fetal oogonia in newborn oocytes in mice. In particular, in the P5 ovary, high levels of HIF1 are expressed in the small oocytes located in the cortical region [ 32 ]. In addition, the ovarian cortex is surrounded by collagen embedded in the primordial follicles [ 33 ].…”