Fibroblast growth factor receptor two (FGFR2) regulates uterine epithelial integrity and fertility in mice.
Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate luminal epithelial (LE) cell proliferation in the adult mouse uterus. This study tested the hypothesis that FGFR2 has a biological role in postnatal development and function of the uterus by conditionally deleting Fgfr2 after birth using progesterone receptor (Pgr)-Cre mice. Adult Fgfr2 mutant female mice were initially subfertile and became infertile with increasing parity. No defects in uterine gland development were observed in conditional Fgfr2 mutant mice. In the adult, Fgfr2 mutant mice possessed a histologically normal reproductive tract with the exception of the uterus. The LE of the Fgfr2 mutant uterus was stratified, but no obvious histological differences were observed in the glandular epithelium, stroma, or myometrium. Within the stratified LE, cuboidal basal cells were present and positive for basal cell markers (KRT14 and TRP63). Nulliparous bred Fgfr2 mutants contained normal numbers of blastocysts on Day 3.5 postmating, but the number of embryo implantation sites was substantially reduced on Day 5.5 postmating. These results support the idea that loss of FGFR2 in the uterus after birth alters its development, resulting in LE stratification and peri-implantation pregnancy loss.
Center for Reproductive Biology, Department of Animal Sciences, Washington State University, Pullman, Washington.
Justyna
J
Filant
Franco J
FJ
DeMayo
James K
JK
Pru
John P
JP
Lydon
Thomas E
TE
Spencer
D000818:Animals; D010064:Embryo Implantation / Q000235:genetics; D020964:Embryo Loss / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics*; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000502:physiology*; D014599:Uterus / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*
C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
endometrium; female reproductive tract; implantation; mice; rodents; uterus