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Am J Physiol Endocrinol Metab 288: E845-E851, 2005. First published December 14, 2004; doi:10.1152/ajpendo.00398.2004
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Effects of recombinant human follicle-stimulating hormone on embryo development in mice

L. J. Edwards, K. L. Kind, D. T. Armstrong, and J. G. Thompson

Research Centre for Reproductive Health, Department of Obstetrics and Gynecology, The University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia, Australia

Submitted 26 August 2004 ; accepted in final form 6 December 2004

We have developed a protocol using recombinant human follicle-stimulating hormone (rhFSH) to induce ovarian stimulation in the mouse to investigate its impact on preimplantation embryo development. Embryos were collected from adult female C57Bl/6 x CBA F1 mice treated with rhFSH (0, 2.5, 5.0, 10.0, or 20.0 IU) or 5 IU equine chorionic gonadotropin (eCG). Embryos were also recovered from nontreated control mice. Embryos were cultured in vitro for 88 h, and the stage of development was morphologically assessed. The allocation of cells to the inner cell mass or trophectoderm of blastocysts was determined by differential nuclear staining. The expression of insulin-like growth factor 2 (IGF-II), the insulin-like growth factor receptor (IGF-II receptor), and vascular endothelial growth factor (VEGF) in blastocysts was measured by real-time RT-PCR. Blastocyst development was reduced in the 10 (72.3 ± 5.1%) and 20 (77.3 ± 5.6%) IU rhFSH groups compared with control embryos (96.7 ± 1.0%). The number of inner cell mass cells was reduced (P < 0.001) in the 5, 10, and 20 IU rhFSH groups and the eCG group compared with control embryos. We did not find any effect of rhFSH treatment on IGF-II, IGF-II receptor, or VEGF expression in blastocysts compared with the control group. eCG treatment, however, significantly increased the expression of IGF-II in blastocysts. These results indicate that ovarian stimulation with rhFSH impairs the in vitro development of preimplantation mouse embryos, and these results may have potential implications for clinical ovarian stimulation during infertility treatment and subsequent embryo quality.

blastocyst; blastomere allocation; mouse; ovarian stimulation; recombinant gonadotropin



Address for reprint requests and other correspondence: J. T. Thompson, Dept. of Obstetrics and Gynecology, Univ. of Adelaide, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia (E-mail:jeremy.thompson{at}adelaide.edu.au)




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R. L. Kelley, K. L. Kind, M. Lane, R. L. Robker, J. G. Thompson, and L. J. Edwards
Recombinant human follicle-stimulating hormone alters maternal ovarian hormone concentrations and the uterus and perturbs fetal development in mice
Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E761 - E770.
[Abstract] [Full Text] [PDF]




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