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Am J Physiol Endocrinol Metab (May 23, 2006). doi:10.1152/ajpendo.00079.2006
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Submitted on February 15, 2006
Accepted on May 11, 2006

Recombinant human follicle stimulating hormone (rhFSH) alters maternal ovarian hormone concentrations and the uterus, and perturbs fetal development in mice

Rebecca L Kelley1, Karen L Kind1*, Michelle Lane1, Rebecca L Robker1, Jeremy G Thompson1, and Lisa J Edwards1

1 Discipline of Obstetrics and Gynaecology, University of Adelaide, The Queen Elizabeth Hospital, Research Centre for Reproductive Health, Woodville, South Australia, Australia

* To whom correspondence should be addressed. E-mail: karen.kind{at}adelaide.edu.au.

Gonadotropins are routinely administered to produce multiple oocytes for clinical in vitro fertilization (IVF) treatment, laboratory research and livestock industries. Studies in mice have shown gonadotropin stimulation using equine chorionic gonadotropin (eCG) affects the endometrium, implantation and fetal development. Evidence from clinical studies also indicates that stimulation with recombinant human follicle stimulating hormone (rhFSH) may be detrimental to the endometrium and implantation rates. We investigated the effect of rhFSH in mice on maternal plasma hormone concentrations and uterine gene and protein expression, and the effect of a stimulated maternal environment on pregnancy. Adult females were stimulated with rhFSH or eCG, followed by human chorionic gonadotropin (hCG). On day 4 of pseudopregnancy mice either had embryos transferred to the uterus or were sacrificed and blood and uterine samples were collected. Pregnancy outcomes were examined on day 15. Gonadotropin stimulation increased plasma progesterone concentrations on day 4 compared to controls, while estradiol concentrations were unaffected. Stimulation also reduced uterine leukemia inhibitory factor (Lif) mRNA, but the expression of estrogen and progesterone receptors (Esr1 and Pgr), homeobox gene Hoxa10 and vascular endothelial growth factor (Vegf) mRNA were unchanged. Furthermore, distribution of uterine PGR protein expression was altered by stimulation, but LIF protein was unchanged. Stimulated embryo transfer recipients had lower pregnancy rates than controls, and fetuses from the rhFSH group had reduced weight, length and maturity. These results demonstrate that gonadotropin stimulation with rhFSH or eCG alters the pre-implantation maternal environment which results in reduced pregnancy rates and fetal development in the mouse.







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