Dataset Information

Gene expression profiling of the paracrine effects of uterine natural killer cells on human endometrial epithelial cells.

ABSTRACT: The endometrium contains a population of immune cells that undergo changes during implantation and pregnancy. The majority of these cells are uterine natural killer (uNK) cells; however, it is unclear how these cells interact with endometrial epithelial cells. Therefore, we investigated the paracrine effects of the uNK cell-secretion medium on the gene expression profile of endometrial epithelial cells in vitro through microarray analysis. Our results, which were verified by qRT-PCR and western blot, revealed that soluble factors from uNK cells alter the gene expression profiles of epithelial cells. The upregulated genes included interleukin-15 (IL-15) and interleukin-15 receptor alpha (IL-15RA), which result in a loop that stimulates uNK cell proliferation. In addition, vascular endothelial growth factor C (VEGF-C) and chemokine (C-X-C motif) ligand 10 (CXCL-10) were also determined to be upregulated in epithelial cells, which suggests that uNK cells work synergistically with epithelial cells to support implantation and pregnancy. In addition, oriental herbal medicines have been used to treat infertility since ancient times; however, we failed to find that Zi Dan Yin can regulate these endometrial paracrine effects.

SUBMITTER: Gong X

PROVIDER: S-EPMC3984803 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Gene expression profiling of the paracrine effects of uterine natural killer cells on human endometrial epithelial cells.

Gong Xin X Chen Zhenzhen Z Liu Yanxia Y Lu Qiudan Q Jin Zhe Z

International journal of endocrinology 20140326

The endometrium contains a population of immune cells that undergo changes during implantation and pregnancy. The majority of these cells are uterine natural killer (uNK) cells; however, it is unclear how these cells interact with endometrial epithelial cells. Therefore, we investigated the paracrine effects of the uNK cell-secretion medium on the gene expression profile of endometrial epithelial cells in vitro through microarray analysis. Our results, which were verified by qRT-PCR and western ...[more]

PMID: 24790599

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Project description:In humans, specific patterns of killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer (uNK) cells are linked through HLA-C with pregnancy complications (infertility, recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia). To identify mechanisms underpinning the associations between NK cell activation and pregnancy success, pregnancies were studied in mice with genetic knockdown (KD) of the MHC-activated Ly49 receptor gene family. B6.Ly49(KD) pregnancies were compared to normal control B6.Ly49(129) and C57BL/6 (B6) pregnancies. At mid-pregnancy (gestation day (gd9.5)), overall uNK cell (TCRβ(-)CD122(+)DBA(+)DX5(-) (DBA(+)DX5(-))) and TCRβ(-)CD122(+)DBA(-)DX5(+) (DBA(-)DX5(+))) frequencies in pregnant uterus were similar between genotypes. Ly49(KD) lowered the normal frequencies of Ly49(+) uNK cells from 90.3% to 47.8% in DBA(-)DX5(+) and 78.8% to 6.3% in DBA(+)DX5(-) uNK cell subtypes. B6.Ly49(KD) matings frequently resulted in expanded blastocysts that did not implant (subfertility). B6.Ly49(KD) mice that established pregnancy had gestational lengths and litter sizes similar to controls. B6.Ly49(KD) neonates, however, were heavier than controls. B6.Ly49(KD) implantation sites lagged in early (gd6.5) decidual angiogenesis and were deficient in mid-pregnancy (gd10.5) spiral arterial remodelling. Ultrastructural analyses revealed that B6.Ly49(KD) uNK cells had impaired granulogenesis, while immunocytochemistry revealed deficient vascular endothelial cell growth factor (VEGFA) production. Perforin and IFNG expression were normal in B6.Ly49(KD) uNK cells. Thus, in normal mouse pregnancies, Ly49 receptor signaling must promote implantation, early decidual angiogenesis and mid-pregnancy vascular remodelling. Disturbances in these functions may underlie the reported genetic associations between human pregnancy complications and the inability of specific conceptus MHCs to engage activating KIR on uNK cells.

Dataset Information

Gene expression profiling of the paracrine effects of uterine natural killer cells on human endometrial epithelial cells.

Publications

Gene expression profiling of the paracrine effects of uterine natural killer cells on human endometrial epithelial cells.

Similar Datasets

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