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Hum. Reprod. Advance Access published online on December 9, 2004
Human Reproduction, doi:10.1093/humrep/deh648
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Human Reproduction © European Society of Human Reproduction and Embryology 2004; all rights reserved
Received December 4, 2003
Revised September 22, 2004
Accepted November 11, 2004

Article

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

R.M. Sibug 1*, J. de Koning 2, A.M.I. Tijssen 2, M.C. de Ruiter 3, E.R. de Kloet 2, and F.M. Helmerhorst 4

1 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; Department of Gynaecology & Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands
2 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
3 Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands and
4 Department of Gynaecology & Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands

* To whom correspondence should be addressed.
R.M. Sibug, E-mail: r.sibug{at}lacdr.leidenuniv.nl


  Abstract

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 (VEGF120) 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.

Keywords: CRH; peri-implantation period; recombinant gonadotrophins; urinary gonadotrophins; VEGF120.
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