Gonadotrophin stimulation reduces VEGF(120) expression in the mouse uterus during the peri-implantation period.
BACKGROUND
Ovarian stimulation by gonadotrophin treatment exerts negative effects on implantation and embryonic development. We investigated whether gonadotrophin treatment affects VEGF(120) mRNA expression during the peri-implantation period.


METHODS
Two groups of adult female CD1 mice were used: the hormone-treated group was injected i.p. with urinary human FSH (5 IU in 0.1 ml saline) and urinary HCG (5 IU in 0.1 ml saline). Spontaneously ovulating mice served as controls and received saline injections. The pregnant mice were killed on embryonic development (ED) days 0, 3, 4, 5 and 6 (day of vaginal plug detection is considered as ED0). The uteri with the implanted embryos were processed for in-situ hybridization for VEGF(120). A separate group of control and hormone-treated pregnant mice were allowed to give birth. Litter size, birthweight and length of gestational period were noted.


RESULTS
Gonadotrophin treatment decreased VEGF(120) mRNA levels, delayed implantation, reduced the size of the embryo implantation site on ED5 and ED6 and prolonged the gestational period.


CONCLUSIONS
Gonadotrophin treatment reduces VEGF(120) expression which may have serious consequences for normal embryonic development. The present data cannot establish whether this effect is a cause or consequence of delayed implantation.
Sibug
R M
RM
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research/Leiden University Medical Center, Gorlaeus Laboratories, P.O.Box 9502, 2300 RA Leiden, The Netherlands. r.sibug@lacdr.leidenuniv.nl
Helmerhorst
F M
FM
Tijssen
A M I
AM
de Kloet
E R
ER
de Koning
J
J
D017398:Alternative Splicing; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects* / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007700:Kinetics; D008098:Litter Size / Q000187:drug effects; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D010062:Ovulation Induction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D006063:Chorionic Gonadotropin; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005640:Follicle Stimulating Hormone