Urinary gonadotrophins but not recombinant gonadotrophins reduce expression of VEGF120 and its receptors flt-1 and flk-1 in the mouse uterus during the peri-implantation period.
BACKGROUND
Ovarian stimulation in humans might affect the perinatal outcome and be considered as a stress factor in the implantation process. In this study we compared the effects of recombinant and urinary gonadotrophins during the mouse peri-implantation period.


METHODS
Adult female CD1 mice were treated as follows (a) urinary hFSH and urinary hCG, (b) recombinant hFSH and recombinant hLH and (c) saline. The effects of the gonadotrophins on the expression of vascular endothelial growth factor120 (VEG120) and its receptors and the corticotrophin releasing hormone (CRH) system during the peri-implantation period were studied. The specific effects of the different gonadotrophins on the onset of implantation were also studied.


RESULTS
Urinary gonadotrophin treatment caused lower levels of VEGF120, flt-1 and flk-1 mRNA levels, reduced the size of the embryo implantation site, delayed implantation and prolonged the gestational period. Both urinary hFSH and urinary hCG contributed to the adverse effects. Levels of CRH and CRHR1 expression were not influenced. Recombinant gonadotrophin treatment did not alter any of the parameters studied.


CONCLUSIONS
Our results show that the VEGF system of the mouse uterus during the peri-implantation period is adversely affected by urinary gonadotrophins but not by recombinant gonadotrophins. The CRH system was not affected by the two types of gonadotrophins.
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
de Koning
J
J
Tijssen
A M I
AM
de Ruiter
M C
MC
de Kloet
E R
ER
Helmerhorst
F M
FM
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000652:urine; D010064:Embryo Implantation; D016326:Extracellular Matrix Proteins; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology / Q000652:urine; D006062:Gonadotropins / Q000494:pharmacology* / Q000652:urine*; D007986:Luteinizing Hormone / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018995:Myosin Heavy Chains; D024501:Nonmuscle Myosin Type IIB; D011506:Proteins / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D006063:Chorionic Gonadotropin; D016326:Extracellular Matrix Proteins; D006062:Gonadotropins; D011506:Proteins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains