Expression and contribution of the HIF-1α/VEGF signaling pathway to luteal development and function in pregnant rats.
Mol Med Rep
; 12(5): 7153-9, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26323652
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 hypoxiainducible factor (HIF)1α in luteal cells cultured in vitro, determined in our previous study, the present study was performed to confirm the hypothesis that HIF1α is induced and then regulates the expression of VEGF and VEGFdependent luteal development/function in vivo. This was investigated using a pregnant rat model treated with a smallmolecule inhibitor of HIF1α, 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 HIF1α and VEGF by reverse transcriptionquantitative 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 HIF1α 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 HIF1α, and subsequent luteal function, which was determined by detecting changes in serum progesterone on days 8 and 14. Taken together, these results demonstrated that HIF1αmediated 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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Cuerpo Lúteo
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Factor A de Crecimiento Endotelial Vascular
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Pregnancy
Idioma:
En
Revista:
Mol Med Rep
Año:
2015
Tipo del documento:
Article