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首页> 外文期刊>Endocrinology >Inhibition of vascular endothelial growth factor in the primate ovary up-regulates hypoxia-inducible factor-1alpha in the follicle and corpus luteum.
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Inhibition of vascular endothelial growth factor in the primate ovary up-regulates hypoxia-inducible factor-1alpha in the follicle and corpus luteum.

机译：抑制灵长类卵巢中的血管内皮生长因子可上调卵泡和黄体中的缺氧诱导因子-1α。

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Vascular endothelial growth factor (VEGF)-dependent angiogenesis is crucial for follicular growth, and corpus luteum formation and function, in the primate ovary. In the ovary VEGF can be hormonally regulated, but in other systems, the main regulator of VEGF expression is hypoxia. We hypothesized that hypoxia was involved in the regulation of angiogenesis in the cycling ovary. We therefore used immunohistochemistry to localize hypoxia-inducible factor (HIF)-1alpha in the marmoset ovary across the ovarian cycle. We also investigated the effect of VEGF inhibition, using VEGF Trap (aflibercept), on HIF-1alpha localization during the follicular and luteal phases of the cycle. Finally, we studied the effect of chorionic gonadotropin stimulation of the corpus luteum during early pregnancy. Nuclear HIF-1alpha staining was largely absent from normally growing preantral and antral follicles. However, there was marked up-regulation of nuclear HIF-1alpha in the granulosa cells at ovulation that persisted into theearly corpus luteum. Mature corpora lutea and those collected during early pregnancy had minimal nuclear HIF-1alpha staining. The inhibition of VEGF in the mid-luteal stage resulted in a time-dependent up-regulation of luteal nuclear HIF-1alpha staining (P 0.05). There was never any nuclear HIF-1alpha in the theca cells of the follicle, but VEGF Trap treatment during the follicular (P 0.001) or luteal (P 0.001) phase increased the proportion of antral follicles with nuclear HIF-1alpha staining in the granulosa cells. These results indicate that HIF-1alpha is up-regulated after vascular inhibition, using VEGF Trap, in the follicle and corpus luteum. However, it is also acutely up-regulated during ovulation. This suggests a role for HIF-1alpha in both hypoxic and hormonal regulation of ovarian VEGF expression in vivo.
机译：血管内皮生长因子（VEGF）依赖性血管生成对于灵长类卵巢中的卵泡生长以及黄体的形成和功能至关重要。在卵巢中，VEGF可以被激素调节，但是在其他系统中，VEGF表达的主要调节剂是低氧。我们假设缺氧参与循环卵巢中血管生成的调节。因此，我们使用免疫组织化学在整个卵巢周期内在the猴卵巢中定位缺氧诱导因子（HIF）-1alpha。我们还研究了在周期的卵泡期和黄体期使用VEGF Trap（aflibercept）抑制VEGF对HIF-1alpha定位的影响。最后，我们研究了绒毛膜促性腺激素在妊娠早期刺激黄体的作用。正常生长的窦前和肛门窦卵泡不存在核HIF-1α染色。然而，排卵时颗粒细胞中的核HIF-1α明显上调，并持续进入黄体早期。成熟的黄体和早孕期间收集的那些细胞核HIF-1alpha染色最少。在黄体中期，VEGF的抑制导致黄体核HIF-1α染色随时间的上调（P <0.05）。在卵泡的卵泡膜细胞中从来没有任何核HIF-1alpha，但是在卵泡期（P <0.001）或黄体期（P <0.001）阶段进行VEGF陷阱治疗会增加卵泡中核HIF-1alpha染色的窦腔卵泡的比例。颗粒细胞。这些结果表明，在使用VEGF Trap的血管抑制后，HIF-1alpha在卵泡和黄体中被上调。但是，它在排卵期也急剧上调。这表明HIF-1alpha在体内缺氧和激素调节卵巢VEGF表达中均起作用。

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