Expression And Elementary Study Of HIF-1α To Trophoblast Invasion Of Placenta In Pregnancy Induced Hypertension

Objective: Hypertension disorder complicating pregnancy is the peculiar disease in pregnancy. It is leading cause of maternal and perinatal morbidity and mortality. The major pathological change is the shallow invasion of trophoblast, but the etiology of pre-eclampsia is unclear. At the initial phase of pregnancy, embryo grows in a relatively hypoxia surrounding. The invasion of the trophoblast to the myometrium anchor the embryo to the uterus, and to the maternal spiral arteries remodel the endothelium and muscle of spiral arteries and expand the blood vessel subsequently build the maternal and fetal blood circulation. About 10 weeks of gestation, invasive trophoblast reach to the muscle of decidual uterine spiral arteries, and remodel the vessels. About 14-20 weeks of gestation, remodeling of uterine spiral arteries penetrate to the 1/3 muscle of uterus. The shallow invasion of trophoblast is the key step of hypertension disorder complicating pregnancy. The reduction of trophoblast invasion capability makes the shallow invasion, deficient remodeling of uterus spiral arteries and insufficient placenta perfusion, which cause destroy of vessel endothelium, finally lead to pre-eclampsia. By now, the mechanism of regulation about trophoblast invasion is unclear, hypoxia is the key point of the trophoblast invasion. Hypoxia could affect trophoblast invasion by inducing the expression of PAI-1,VEGF,TGF-β3 and increasing the active oxygen production; hypoxia could adjust the trophoblast invasion by stopping cytotrophblast differentiation to invasive phenotype. Thus induce the preeclampsia. Recently there are some abroad laboratories have made progress in the study of HIF-1αin the etiology of preeclampsia. Maternal G found that HIF-1αworks in ET-1 in chronic hypoxia surroundings, activates the gene expression of ET-1 and causes the constriction of the blood vessel. Caniggia I detected that the expression of HIF-1αis increased in hypertension disorder complicating pregnancy, they presumed that HIF-1 αcould influences the invasion of trophoblast and induces the occurrence of hypertension disorder complicating pregnancy. However, there are not associated reports at home. This study was designed to investigate and compare the expression of hypoxia inducible factor-1α(HIF-1α) to trophoblast of placenta in early pregnancy, normal pregnancy and preeclampsia. The difference of the invasion capability and growth characteristics between the two groups of thrphoblast in vitro was compared, which were cultured in normal oxygen and hypoxia (3% O2) surrounding respectively. This study will help to illuminate the process of patho-physiology of hypertension disorder complicating pregnancy, to supply some theoretic foundation about regulation of trophoblast invasion and to supply some new method about early diagnosis/ prevention/ treatment of preeclampsia. Methods: 1. Placenta of early pregnancy, preeclapsia and control group were collected, freezing slice and immunohistochemical streptavidin biotinperoxidase complex technique (SABC) were used to examine the expression of HIF-1 αamong the three groups. In situ hybridization was used to examine the expression of HIF-1αamong three groups. Image analysis was used to detect the differentiation of three groups. 2. Tissue-culture method was used to get the primary human trophoblastic cells of first trimester pregnancy. The Ficoll separation and different speed adherence was used to purify the cells, immunocytochemistry with specific CK7 and viminten monoclonal antibodies was used to identified the cells. Trophoblast was cultured in normal oxygen and hypoxia surroundings, the Matrigel were used to compare the invasive capability between the two groups. MTT was used to detect the differentiation of growth in two groups. Results: 1. The expression of placental HIF-1αprotein in control group decreased significantly, Increasing expression of HIF-1αwas observed from the preeclampsia group and early pregnancy group. There was not significant difference between treatment group and control, and there was not significant difference among three groups of hypertension disorder complicating pregnancy. The expression of placental HIF-1αmRNA increased remarkably in the preeclampsia group and early pregnancy group, but in normal pregnancy group it decreased. 2. Increasing invasion capacity and decreasing proliferation ability were observedwhen the trophoblast were cultured under normal oxygen surroundings, but decreasing invasion capacity and increasing proliferation ability under hypoxia culture surroundings. Conclusion: 1. The expression of HIF-1αand its mRNA were increased in villous of earlier pregnancy and placenta of hypertension disorder complicating pregnancy, but decreased in normal gestation placenta, which indicates HIF-1αmay have a continuous high expression during the overall procedure of lamentation and etiology of hypertension disorder complicating pregnancy and relate to its occurrence and development. In hypertension disorder complicating pregnancy placenta, the expression of HIF-1αhad nothing to do with the disease's severity and treatment, which indicates the main cause of high expression of HIF-1αmay not be the hypoxia caused by decrease of blood perfusion in placenta, but the relative and absolute hypoxia conditions of earlier placentation. 2. The facts that high expression of trophoblasts's HIF-1αin hypoxia conditions, increased proliferative capability, decreased invasive capability and concordance of time and degree between the expression and secretion of HIF-1αand the proliferation and invasion of trophoblasts indicate that high expression of trophoblasts's HIF-1αcaused by hypoxia conditions may be closely related to their decreased invasive capability and increased proliferative capability, thus become one of the main causes of shallow invasion of placenta in preeclampsia.