Molecular Human Reproduction, Vol. 7, No. 3, 255-264,
March 2001
© 2001 European Society of Human Reproduction and Embryology
Testis and spermatogenesis |
Vascular endothelial growth factor transgenic mice exhibit reduced male fertility and placental rejection
1 Molecular Angiogenesis Laboratory, Imperial Cancer Research Fund, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, 2 In Situ Histopathology Unit, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, 3 Department of Histopathology, Division of Investigative Sciences, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, and 4 Molecular Oncology Laboratory, Imperial Cancer Research Fund, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
Abstract
Recent evidence points to the involvement of vascular endothelial growth factor (VEGF) in mammalian reproductive physiology. Transgenic mice expressing VEGF (121 isoform) under the control of the polyepithelial mucin-1 (muc-1) promoter showed a reduction in male fertility due to impaired spermiogenesis, and aberrant placentation leading to preferential rejection of male embryos. A skew in the sex ratio of the litters was seen (three females to two males), independently of whether the transgene was carried by the male or female parent. In-situ hybridization permitted distinction of expression of the human VEGF transgene from endogenous mouse VEGF, and confirmed expression of the transgene in a wide range of epithelial tissues. Expression of the transgene in spermatocytes and in the embryonic portion of placenta is thought to be responsible for the reduced fertility and embryonic resorptions respectively. Males showed either complete sperm maturation arrest or various gradations of partial fertility. Abnormally high or low VEGF in human semen has been reported to be correlated with a lack of pregnancy success following IVF. The muc1-VEGF (121 isoform) transgenic mouse provides an animal model with which to further study this VEGF-induced pathology.
epithelial mucin/testis/transgenic mice/VEGF
Notes
5 To whom correspondence should be addressed. E-mail: r.bicknell{at}icrf.icnet.uk
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