Expression of vascular endothelial growth factor (VEGF) and its receptors in human endometrium throughout the menstrual cycle and in early pregnancy.
Immunohistochemistry for vascular endothelial growth factor (VEGF) and its receptors, fms-like tyrosine kinase (flt-1) and kinase insert domain-containing region (KDR), was performed on human endometrium obtained from patients with normal menstrual cycles, patients given oestrogen and progesterone, and women in early pregnancy. Intense immunostaining of VEGF was observed in both glandular epithelial and stromal cells during the mid-secretory phase; the immunostaining intensity was increased by administration of oestrogen plus progesterone and strong immunostaining was observed in decidual cells of early pregnancy. In addition to the immunostaining in vascular endothelial cells, strong KDR immunostaining was observed in glandular epithelial cells and in decidualized stromal cells induced by administration of oestrogen plus progesterone, whereas flt-1 immunostaining was negligible. Strong immunostaining for flt-1 and KDR was found in both vascular endothelial cells and decidual cells in early pregnancy. Endometrial stromal cells isolated from proliferative phase endometrium were incubated with oestrogen (10(-8) mol l-1) and medroxyprogesterone acetate (MPA; 10(-6) mol l-1) for 18 days to study the regulation of VEGF, flt-1 and KDR in endometrial stromal cells by oestrogen and progesterone. Expression of VEGF and KDR mRNAs was increased significantly by oestrogen and MPA, accompanied by decidualization, whereas flt-1 mRNA expression was not affected. In conclusion, VEGF and its receptors may play important roles in implantation and maintenance of pregnancy.
Sugino
N
N
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan. obgyn@po.cc.yamaguchi-u-ac.jp
Kashida
S
S
Karube-Harada
A
A
Takiguchi
S
S
Kato
H
H
D000328:Adult; D000704:Analysis of Variance; D002478:Cells, Cultured; D003656:Decidua / Q000737:chemistry / Q000378:metabolism; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D011247:Pregnancy / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000737:chemistry / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004967:Estrogens; D016326:Extracellular Matrix Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017258:Medroxyprogesterone Acetate; C501162:FLT1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1