265. Gonadotrophic hormones affect the uterus, implantation and fetal development in mice
R. L. Kelley A , K. L. Kind A , M. Lane A , R. L. Robker A , J. G. Thompson A and L. J. Edwards AResearch Centre for Reproductive Health, University of Adelaide, Woodville, SA, Australia
Reproduction, Fertility and Development 17(9) 108-108 https://doi.org/10.1071/SRB05Abs265
Submitted: 26 July 2005 Accepted: 26 July 2005 Published: 5 September 2005
Abstract
Although gonadotrophin stimulation using equine chorionic gonadotrophin (eCG) adversely influences pregnancy and fetal development, the effects of stimulation using recombinant human follicle stimulating hormone (rhFSH) are largely unknown. Evidence from human studies indicates that rhFSH may also be detrimental to the endometrium and implantation. We investigated the effect of gonadotrophin stimulation on ovarian hormones and uterine characteristics in the peri-implantation period, and pregnancy outcomes in mice. Adult female mice were stimulated with 2.5 IU or 10 IU rhFSH or 5 IU eCG, followed by 5 IU human chorionic gonadotrophin (hCG). Control mice received saline injections. On day 4 of pseudopregnancy mice either had embryos transferred to the uterus or were sacrificed and blood and uterine samples collected. Plasma progesterone and estradiol concentrations were determined by radioimmunoassay. Uterine mRNA levels of the estrogen and progesterone receptors (ERa and PR), leukaemia inhibitory factor (LIF), homeobox gene Hoxa10 and vascular endothelial growth factor (VEGF) were determined by real-time RT-PCR. Uterine protein distribution of PR was determined by immunohistochemistry. Embryo transfer recipients were sacrificed on day 15 to assess pregnancy outcomes. Gonadotrophin stimulation increased plasma progesterone concentration compared to controls, while estradiol concentrations were not affected. Stimulation also reduced total LIF mRNA and altered the spatial distribution of PR protein in the uterus on day 4. Embryo transfer recipients administered eCG or 10IU rhFSH had lower pregnancy rates compared to controls (11, 35 and 75% respectively) and fetuses from the rhFSH group had reduced mean weight (94 ± 6 v. 176 ± 8 mg), length (11 ± 0.2 v. 12 ± 0.1 mm) and maturity (14.1 ± 0.09 v. 14.6 ± 0.05 days) compared to controls. These results demonstrate that gonadotrophin stimulation induces changes to the maternal reproductive tract prior to implantation that have consequences for the establishment of pregnancy and fetal development in the mouse.
