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Fertil Steril. 2019 Dec;112(6):1118-1128. doi: 10.1016/j.fertnstert.2019.08.060.

Macrophages display proinflammatory phenotypes in the eutopic endometrium of women with endometriosis with relevance to an infectious etiology of the disease.

Author information

1
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California; Department of Gynecology, IVIRMA Barcelona S.L., Barcelona, Spain; Group of Biomedical Research in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain.
2
Department of Gynecology, IVIRMA Barcelona S.L., Barcelona, Spain; Group of Biomedical Research in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain; Igenomix, Valencia, Spain.
3
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California.
4
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California. Electronic address: linda.giudice@ucsf.edu.

Abstract

OBJECTIVE:

To phenotype transcriptomically M1 macrophages (Mϕ1) and M2 macrophages (Mϕ2) in the endometrium of women with endometriosis.

DESIGN:

Prospective experimental study.

SETTING:

University research laboratory.

PATIENT(S):

Six women with endometriosis and five controls without disease, in the secretory phase of the menstrual cycle.

INTERVENTION(S):

Mϕ1, Mϕ2, uterine natural killer, and T regulatory cells were isolated from human endometrium using a uniquely designed cell-specific fluorescence activating cell sorting panel. Transcriptome profiles were assessed by RNA high sequencing, bioinformatics, and biological pathway analyses.

MAIN OUTCOMES MEASURE(S):

Differential gene expression between Mϕ1 and Mϕ2 in women with and without endometriosis and in Mϕ1 versus Mϕ2 in each group was determined and involved different biologic and signaling pathways.

RESULT(S):

Flow cytometry analysis showed no significant differences in total numbers of leukocytes between control and endometriosis groups, although Mϕ1 were higher in the endometriosis group versus controls. Statistical transcriptomic analysis was performed only in Mϕ1 and Mϕ2 populations due to larger sample sizes. Bioinformatic analyses revealed that in women with endometriosis, endometrial Mϕ1 are more proinflammatory than controls and that Mϕ2 paradoxically have a proinflammatory phenotype.

CONCLUSION(S):

As Mϕ are phenotypically plastic and their polarization state depends on their microenvironment, the altered endometrial environment in women with endometriosis may promote endometrial Mϕ2 polarization and an Mϕ1 proinflammatory phenotype. Moreover, aberrant phenotypes of Mϕ may contribute to abnormal gene expression of the eutopic endometrium and a proinflammatory environment in women with endometriosis relevant to the pathophysiology of the disease and compromised reproductive outcomes.

KEYWORDS:

Endometriosis; endometrium; infection; inflammation; macrophages

PMID:
31843088
PMCID:
PMC6944306
[Available on 2020-12-01]
DOI:
10.1016/j.fertnstert.2019.08.060

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