Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation.

Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation.
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DOI:
10.1038/srep38078
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发表时间:
2016-12-01
期刊:
影响因子:
4.6
通讯作者:
Spencer TE
Spencer TE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kelleher AM;Burns GW;Behura S;Wu G;Spencer TE

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子宫腺对小鼠和可能的人类妊娠至关重要,因为它们分泌或运输生物活性物质,调节子宫对囊胚着床的接受性。在小鼠中,子宫在第4天变得可接受囊胚着床,但在第5天变得难治性。在这里,孕激素诱导的子宫腺(PUGKO)在交配后第5天可以恢复囊胚,而野生型(WT)小鼠则不能。PUGKO的管腔上皮存在抗黏附Muc1蛋白和微绒毛,而WT的子宫上皮不存在。许多已知的子宫接受性基因和腺体特异性基因在PUGKO子宫中发生改变。然后于第3、4、5天分别取WT和PUGKO小鼠的子宫和子宫腔液(ULF)。转录组分析显示,PUGKO子宫中580个基因减少,而ULF血清组分析显示,PUGKO子宫中许多蛋白质和几种氨基酸增加。值得注意的是,在WT小鼠的ULF中没有发现许多由许多腺体特异性基因编码的蛋白质。这些结果支持了子宫腺分泌调节ULF稳态的因子,并与子宫内其他细胞类型相互作用,影响子宫接受性和囊胚着床以建立妊娠的观点。
Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. In mice, the uterus becomes receptive to blastocyst implantation on day 4, but is refractory by day 5. Here, blastocysts could be recovered from progesterone-induced uterine gland (PUGKO) but not wildtype (WT) mice on day 5 post-mating. Anti-adhesive Muc1 protein and microvilli were present on the luminal epithelium of PUGKO but not WT uteri. A number of known uterine receptivity genes and gland-specific genes were altered in the PUGKO uterus. Next, the uterus and uterine luminal fluid (ULF) were obtained from WT and PUGKO mice on day 3, 4 and 5. Transcriptome analysis revealed that 580 genes were decreased in the PUGKO uterus, however ULF secrotome analysis revealed that many proteins and several amino acids were increased in the PUGKO ULF. Of note, many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice. These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy.
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