Placental overgrowth and fertility defects in mice with a hypermorphic allele of epidermal growth factor receptor |
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Authors: | Jennifer Dackor Manyu Li David W Threadgill |
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Institution: | (1) Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA;(2) Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC 27599, USA;(3) Department of Genetics, North Carolina State University, Campus Box 7614, Raleigh, NC 27695, USA |
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Abstract: | Epidermal growth factor receptor (EGFR) is a member of the ERBB family of receptor tyrosine kinases that has been shown to
play an important developmental and physiologic role in many aspects of pregnancy. We have previously shown in mice that Egfr
tm1Mag
nullizygous placentas have fewer proliferative trophoblasts than wild-type and exhibit strain-specific defects in the spongiotrophoblast
and labyrinth layers. In this study we used mice with the hypermorphic Egfr
Dsk5
allele to study the effects of increased levels of EGFR signaling on placental development. On three genetic backgrounds,
heterozygosity for Egfr
Dsk5
resulted in larger placental size with a more prominent spongiotrophoblast layer and increased expression of glycogen cell-specific
genes. The C3HeB/FeJ strain showed additional placental enlargement of Egfr
Dsk5
homozygotes with a significant number of homozygous embryos dying prior to 15.5 days post-coitus (dpc). We also observed
strain-specific subfertility in Egfr
Dsk5
heterozygous females and pregnancy loss was dependent on maternal factors rather than embryo genotype. Higher levels of phospho-EGFR
were detected in the uterus of Egfr
Dsk5
heterozygotes but the structure of Egfr
Dsk5
heterozygous nonpregnant uteri appeared similar to wild-type. Collectively, our results demonstrate that mice with increased
levels of EGFR signaling exhibit an extensive level of genetic background-dependent phenotypic variability. In addition, EGFR
promotes growth of the placental spongiotrophoblast layer in mice, and EGFR expressed in the uterine stroma may play an underappreciated
role in preparation of the uterus for embryo implantation. |
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Keywords: | |
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