This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sengupta, J Articles by Ghosh, D Search for Related Content PubMed PubMed Citation Articles by Sengupta, J Articles by Ghosh, D

Immunoneutralization of vascular endothelial growth factor inhibits pregnancy establishment in the rhesus monkey (Macaca mulatta)

Department of Physiology, All India Institute of Medical Sciences, New Delhi 110029, India, ¹ Department of Obstetrics and Gynecology, University of Cambridge, Cambridge CB2 2SW, UK and ² Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK

Correspondence should be addressed to D Ghosh; Email: dghosh{at}aiims.ac.in

Maternal endometrial vascular endothelial growth factor (VEGF) is considered important in blastocyst implantation. However, there is no direct evidence to support this conjecture in the primate. In the present study, we have examined this hypothesis by testing whether immunoneutralization of VEGF during the peri-implantation stage of gestation affects embryo implantation in the rhesus monkey. Adult female animals (n = 36) during mated ovulatory cycles were randomly assigned to one of the experimental groups treated subcutaneously with either isotype-matched mouse immunoglobulin (group 1: control, n = 8) or monoclonal mouse antibody against VEGF-A (anti-VEGF Mab; group 2: 10 mg on day 5 after ovulation, n = 8; group 3: 20 mg on day 5 after ovulation, n = 8; group 4: 10 mg on day 10 after ovulation, n = 4; group 5: 10 mg on days 5 and 10 after ovulation, n = 8). Anti-VEGF Mab-treated animals in groups 2–4 did not show any marked inhibition in pregnancy establishment. On pooled analysis, however, anti-VEGF Mab administration in groups 2–5 (n = 28) resulted in a significant (P < 0.04) decline in the number of viable term pregnancy when compared with control animals. The observed difference was explained by the fact that 10 mg anti-VEGF Mab given to each animal on days 5 and 10 after ovulation in group 5 (n = 8) inhibited pregnancy establishment significantly (P < 0.02) when compared with control group 1. There was no significant change in serum concentrations of estradiol-17ß, progesterone, and free VEGF among groups. Furthermore, animals treated with anti-VEGF Mab (n = 8) as in group 5 revealed marked decrease in immunoreactive VEGF, fms-like tyrosine kinase-1, and kinase-insert domain region in trophoblast cells associated with shallow uterine invasion on day 13 of gestation when compared with samples from control group animals (n = 8). Thus, VEGF action is required for successful blastocyst implantation in the rhesus monkey.