Fibroblast growth factor receptor two (FGFR2) regulates uterine epithelial integrity and fertility in mice.

Fibroblast growth factor receptor two (FGFR2) regulates uterine epithelial integrity and fertility in mice.
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DOI:
10.1095/biolreprod.113.114496
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发表时间:
2014-01
影响因子:
3.6
通讯作者:
Spencer TE
Spencer TE
中科院分区:
生物学2区
文献类型:
--
作者:
Filant J;DeMayo FJ;Pru JK;Lydon JP;Spencer TE

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成纤维细胞生长因子(FGF)及其受体(FGFR)调节成年小鼠子宫腔上皮(LE)细胞增殖。本研究通过孕激素受体(Pgr)-Cre小鼠在出生后有条件地去除Fgfr 2,验证了FGFR 2在出生后子宫发育和功能中具有生物学作用的假设。AdultFgfr 2突变雌性小鼠最初生育力低下,随着产次的增加而变得不育。在条件性Fgfr 2突变小鼠中未观察到子宫腺发育缺陷。在成年时,Fgfr 2突变小鼠具有组织学正常的生殖道,子宫除外。Fgfr 2突变子宫的LE呈分层,但在腺上皮、间质或子宫肌层中未观察到明显的组织学差异。在分层LE内,存在立方基底细胞,并且基底细胞标志物(KRT 14和TRP 63)呈阳性。未产bredFgfr 2突变体在交配后第3.5天含有正常数量的囊胚,但在交配后第5.5天胚胎着床位点的数量大幅减少。这些结果支持出生后子宫中FGFR 2的缺失改变其发育,导致LE分层和围着床期妊娠丢失的观点。
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 deletingFgfr2 after birth using progesterone receptor (Pgr)-Cre mice. AdultFgfr2 mutant female mice were initially subfertile and became infertile with increasing parity. No defects in uterine gland development were observed in conditionalFgfr2 mutant mice. In the adult,Fgfr2 mutant mice possessed a histologically normal reproductive tract with the exception of the uterus. The LE of theFgfr2 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 bredFgfr2 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.
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