Effect of HIF-1a/VEGF signaling pathway on plasma progesterone and ovarian prostaglandin F₂a secretion during luteal development of pseudopregnant rats.
The corpus luteum is a temporary endocrine structure in mammals that plays an important role in the female reproductive cycle and is formed from a ruptured and ovulated follicle with rapid angiogenesis. Vascular endothelial growth factor (VEGF) is thought to be vital in normal and abnormal angiogenesis in the ovary, but the molecular regulation of luteal VEGF expression during corpus luteum development in vivo is still poorly understood at present. Therefore, we examined whether hypoxia-inducible factor-1a (HIF-1a) is induced and regulates VEGF expression and luteal function in vivo using a pseudopregnant rat model treated with a small-molecule inhibitor of HIF-1a, echinomycin. Corpus luteum development in the pseudopregnant rat ovary was determined after measuring plasma progesterone concentration and ovarian prostaglandin F2a content to reflect changes in HIF-1a and VEGF on different days of this developmental process. At day 7, the corpus luteum was formed and the expression of HIF- 1a/VEGF reached a maximum, while a significant decrease in HIF-1a/ VEGF expression was observed when luteolysis occurred at day 13. Additionally, echinomycin blocked luteal development by inhibiting VEGF expression mediated by HIF-1a and following luteal function by detecting the progesterone changes at day 7. These results demonstrated that HIF-1a-mediated VEGF expression might be an important mechanism regulating ovarian luteal development in mammals in vivo, which may provide new strategies for fertility control and for treating some types of ovarian dysfunction, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, and ovarian neoplasia.
Provincial Key Laboratory for Developmental Biology and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou, China.
X Y
XY
Pan
Provincial Key Laboratory for Developmental Biology and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou, China.
Z H
ZH
Zhang
Department of Pathophysiology, Maternal and Child Health Hospital of Fujian Province, Fuzhou, China.
L X
LX
Wu
Provincial Key Laboratory for Developmental Biology and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou, China.
Z C
ZC
Wang
D000818:Animals; D003338:Corpus Luteum / Q000254:growth & development* / Q000378:metabolism; D003340:Corpus Luteum Maintenance; D015237:Dinoprost / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D010053:Ovary / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood*; D011555:Pseudopregnancy / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D011374:Progesterone; D015237:Dinoprost