Contribution of hypoxia‐inducible factor‐1α to transcriptional regulation of vascular endothelial growth factor in bovine developing luteal cells

Zhang, Zhenghong; Yin, Dingzhong; Wang, Zhengchao

doi:10.1111/j.1740-0929.2010.00832.x

Cited by 39 publications

(61 citation statements)

References 37 publications

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“…The ruptured follicle, which occurs immediately following ovulation is considered to be under hypoxia conditions due to bleeding and immature vasculature (6). Previous studies have indicated that hypoxia is important for establishing the vascular system during luteal development (5), which induces the expression of hypoxia-inducible factor (HIF)-1α in luteal cells (7)(8)(9)(10)(11). When vascular endothelial factor (VEGF) is regulated by hypoxia, there is an upregulation of specific transcription factors, notably HIF-1α (7,8,12).…”

Section: Introductionmentioning

confidence: 99%

Expression and contribution of the HIF‑1α/VEGF signaling pathway to luteal development and function in pregnant rats

Zhang

Pan

et al. 2015

Mol Med Report

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Abstract. Vascular endothelial growth factor (VEGF) is vital in normal and abnormal angiogenesis in the ovary, particularly during the early development of the corpus luteum in the ovary. However, the molecular regulation of the expression VEGF during luteal development in vivo remains to be fully elucidated. As the expression of VEGF is mediated by hypoxia-inducible factor (HIF)-1α in luteal cells cultured in vitro, determined in our previous study, the present study was performed to confirm the hypothesis that HIF-1α is induced and then regulates the expression of VEGF and VEGF-dependent luteal development/function in vivo. This was investigated using a pregnant rat model treated with a small-molecule inhibitor of HIF-1α, echinomycin (Ech). The development of the corpus luteum in the pregnant rat ovary was identified via performing assays of the serum progesterone, testosterone and estradiol concentrations by radioimmunoassay, accompanied with determination of the changes in the expression levels of HIF-1α and VEGF by reverse transcription-quantitative polymerase chain reaction at different days of the developmental process. On day 5, serum progesterone levels were markedly increased, whereas serum levels of testosterone and estradiol did not change significantly. On day 17, the highest level of serum progesterone was observed, however, this was not the case for testosterone and estradiol. Further analysis of the expression levels of HIF-1α and VEGF revealed that their changes were consistent with the changes in serum levels of progesterone, which occurred in the development of the corpus luteum in the ovaries of pregnant rats. Further investigation demonstrated that Ech inhibited luteal development through inhibiting the expression of VEGF, mediated by HIF-1α, and subsequent luteal function, which was determined by detecting changes in serum progesterone on days 8 and 14. Taken together, these results demonstrated that HIF-1α-mediated expression of VEGF may be one of the important mechanisms regulating ovarian luteal development in mammals in vivo, which may provide novel strategies in treatment for fertility control and for certain types of ovarian dysfunction, including polycystic ovarian syndrome, ovarian hyperstimulation syndrome and ovarian neoplasia.

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Section: Introductionmentioning

confidence: 99%

Expression and contribution of the HIF‑1α/VEGF signaling pathway to luteal development and function in pregnant rats

Zhang

Pan

et al. 2015

Mol Med Report

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“…Furthermore, hypoxia-induced increase of HIF-1α implies that transcriptional regulation of VEGF may be mediated through activation of HIF-1α because this hypoxia-induced upregulation of VEGF mRNA was suppressed by HIF-1α inhibition with ferrous ammonium sulfate in luteal cells (4,7). Thus, O 2 appears to be a major regulator of VEGF expression in the bovine (7,8), ovine (3), and caprine ovaries during the periovulatory period.…”

Section: Discussionmentioning

confidence: 99%

“…During ovulation and early CL formation, VEGF mRNA expression increased significantly under hypoxia, indicating that the hypoxia-induced increase of HIF-1α regulated the transcription of VEGF (7,8). Although VEGF and HIF-1α have key roles in angiogenesis in the ovary by which VEGF is upregulated by HIF-1α under gonadotropin-stimulated conditions, the expression of these angiogenic factors during the periovulatory period remains speculative, except for a handful of species such as sheep (3) and cows (7).…”

Section: Introductionmentioning

confidence: 99%

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Expression of vascular endothelial growth factor and hypoxia-inducible factor-1 alpha during the periovulatory period in goats

Navanukraw¹,

Thammasiri²,

Moonmanee³

et al. 2014

Turk J Vet Anim Sci

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To evaluate the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF-1α) during the periovulatory period, goat ovaries were collected at 0, 4, 8, 12, 24, and 48 h after treatment with 300 IU hCG. Total cellular RNA was isolated and VEGF and HIF-1α were quantified using real-time RT-PCR. The mRNA levels of VEGF in thecal tissue remained unchanged prior to ovulation. However, the mRNA levels of VEGF in thecal tissues at 48 h increased to 7.5-fold of the level at 0 h (P < 0.05). In granulosa tissue, the VEGF mRNA levels were not detected in granulosa cells at 48 h. In thecal tissue, the mRNA level of HIF-1 1α at 4 h was 1.5-fold of the level at 0 h and remained unchanged during 8-24 h; however the levels were significantly increased at 48 h. The mRNA levels of HIF-1α in granulosa at 4 h was not changed but levels were increased (P < 0.05) at 8 h and at 12 h and then decreased at 24 and 48 h, respectively. These data describe the relationships of VEGF-and HIF-1α-dependent angiogenesis during the periovulatory periods by which hypoxia during ovulation is crucial for establishing the thecal new vasculature.

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“…This feature of HIF1p regulation could be unique to the ovary. It is also increasingly apparent that any induction of HIF1pstimulates VEGFA expression in luteal cells (Zhang et al 2011). What is less well known is the role of hypoxia and/or HIF1pin the regulation of FGF2.…”

mentioning

confidence: 99%

The critical importance of ovarian angiogenesis

Robinson¹

2013

Reprod. Fertil. Dev.

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Contribution of hypoxia‐inducible factor‐1α to transcriptional regulation of vascular endothelial growth factor in bovine developing luteal cells

Cited by 39 publications

References 37 publications

Expression and contribution of the HIF‑1α/VEGF signaling pathway to luteal development and function in pregnant rats

Expression and contribution of the HIF‑1α/VEGF signaling pathway to luteal development and function in pregnant rats

Expression of vascular endothelial growth factor and hypoxia-inducible factor-1 alpha during the periovulatory period in goats

The critical importance of ovarian angiogenesis

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