Increased uNK Progenitor Cells in Women With Endometriosis and Infertility are Associated With Low Levels of Endometrial Stem Cell Factor

Thiruchelvam U, Uma Thiruchelvam, Mary Wingfield, Cliona O'Farrelly, Cliona O’Farrelly
American journal of reproductive immunology (New York, N.Y. : 1989) · 2016 · vol. 75(4) , pp. 493–502 · doi:10.1111/aji.12486 · PMID:26791471 · W2334096357
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Women with endometriosis and infertility exhibit increased early-stage uterine natural killer cell progenitors associated with lower endometrial stem cell factor levels, which impairs maturation.

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Abstract

PROBLEM: Uterine natural killer (uNK) cells play a significant role in successful human pregnancy. Having previously demonstrated uNK cell progenitors in human endometrium, we hypothesized that abnormal uNK cell maturation contributes to infertility in women with endometriosis. We aimed to characterize uNK cells at different developmental stages in women with and without endometriosis and to investigate possible mechanisms to explain any differences. METHOD OF STUDY: We characterized uNK cell development in women with and without endometriosis using flow cytometry, protein array and in vitro experiments. RESULTS: We found increased proportions of uNK cells at developmental stages 1 and 2 in endometrium from women with endometriosis (n = 36; mean = 21.2%) when compared with healthy fertile women (n = 9; mean = 7.0%). Protein array analysis revealed significantly lower levels of stem cell factor (SCF) in the eutopic endometrium of women with endometriosis when compared to healthy women. Addition of SCF to endometrial progenitor cells in vitro restored uNK cell maturation. CONCLUSION: We have shown that women with endometriosis have low levels of endometrial SCF, which we hypothesize contributes to abnormal maturation of local uNK cell populations. This defect may also compromise embryo implantation and hence contribute to endometriosis-associated infertility. SCF replacement may be a new therapeutic approach.

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Condition tags

endometriosisinfertility

MeSH descriptors

Endometriosis Endometrium Infertility, Female Killer Cells, Natural Lymphoid Progenitor Cells Stem Cell Factor Adult Endometriosis Endometriosis Endometrium Endometrium Female Humans Infertility, Female Infertility, Female Killer Cells, Natural Killer Cells, Natural Lymphoid Progenitor Cells Lymphoid Progenitor Cells Pregnancy

Funding

funders
[{'doi': '10.13039/501100001590', 'name': 'Health Research Board', 'awards': ['HRA/POR/2012/37']}]

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (98)

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