Expression of hypoxia-inducible factor-1α during ovarian follicular growth and development in Sprague-Dawley rats

Abstract

ABSTRACT. Hypoxia-inducible factor-1α (HIF-1α) has been identified as a transcription factor that is involved in diverse physiological and pathological processes in the ovary. In this study, we examined whether HIF-1α is expressed in a cell-and stage-specific manner during follicular growth and development in the mammalian ovaries. Using immunohistochemistry and Western blot analysis, HIF-1α expression was observed in granulosa cells specifically and was significantly increased during the follicular growth and development of postnatal rats. Furthermore, pregnant mare serum gonadotropin also induced HIF-1α expression in granulosa cells and ovaries during the follicular development of immature rats primed with gonadotropin. Moreover, we also examined proliferation cell nuclear antigen, a cell proliferation marker, during follicular growth and development and found that its expression pattern was similar to that of HIF-1α protein. Granulosa cell culture experiments revealed that proliferation cell nuclear antigen expression may be regulated by HIF-1α. These results indicated that HIF-1α plays an important role in the follicular growth and development of these 2 rat models. The HIF-1α-mediated signaling pathway may be an important mechanism regulating follicular growth and development in mammalian ovaries in vivo.

HIF1 driven transcriptional activity regulates steroidogenesis and proliferation of bovine granulosa cells

“…Therefore, HIF1A levels reported in developing ovarian follicles 14,15,32 and in the cultured GC 22 could be because of the actions of FSH and IGF1 signaling. However, other endocrine factors such as pregnant mare serum gonadotropins also shown to induce HIF1A expression in ovarian follicle 13 , suggesting the physiological state of the animals plays a role in HIF1A expression in ovary.…”

“…PCNA and CCND2 are well known positive markers of cell proliferation in many cells. In the ovary, both genes might play an essential role in follicular maturation as the proliferation of GC is an essential feature of follicular growth and development 13 . Moreover, CCND2 and PCNA have been used in a number of studies to mark the www.nature.com/scientificreports www.nature.com/scientificreports/ proliferation status of GC in-vitro and in-vivo 42,50,51 .…”

“…HIF1 regulates multiple genes in GC and contributes to the ovarian follicle development and differentiation. Zhang et al (2015) have shown that knockdown of HIF1A mRNA abundance downregulates the PCNA (proliferator cell nuclear antigen) mRNA expression under normoxic conditions in rat primary GC 13 , similar to renal medullary interstitial cells of rats 5 . Alam et al (2004) reported that FSH (follicle stimulating hormone) mediated upregulation of genes involved in follicle differentiation such as VEGFA (vascular endothelial growth factor A), LHCGR (Luteinizing Hormone/Choriogonadotropin Receptor) and INHBA (inhibin-α) is dependent on HIF1 activity in rats 16 .…”

“…Transcriptome analysis in pigs indicated that HIF1A expression is downregulated in atretic follicles compared to medium sized healthy antral follicles 10 . Expression of HIF1A was reported in granulosa cells (GC) of different species including human 11 , mice 12 , rat 13 , pigs 14 and cows 15 . Kim et al (2009) have shown that HIF1 is essential for ovulation process as inhibition of HIF1 activity using echinomycin, a competitive inhibitor of HIF1, caused an anovulatory phenotype in mice 12 .…”

Bidirectional Estrogen-Like Effects of Genistein on Murine Experimental Autoimmune Ovarian Disease

“…When genistein effects relate to proliferation, it was meaningful to determine the expression profiles of proliferation markers like PCNA [39]. In the ovary, the expression of PCNA may affect follicular growth by regulating PCNA-dependent granulose cell proliferation in follicles [40]. In the present study, PCNA was mainly expressed in the ovarian follicles.…”