A History of Endometriosis Is Associated With Decreased Peripheral NK Cytotoxicity and Increased Infiltration of Uterine CD68+ Macrophages

Abstract

Women with endometriosis may have a defective immune system. However, evidence of the immune responses of endometriosis patients with a history of endometriosis surgery is lacking, and the association between the location of endometriosis lesions and immune responses is unclear. This retrospective study included 117 females with reproductive failure and a history of endometriosis and 200 females with reproductive failure but without endometriosis to analyze their endometrial and peripheral immune responses. The results show that endometriosis was associated with decreased peripheral natural killer (NK) cytotoxicity and increased uterine macrophages. Peripheral NK cytotoxicity at effector-to-target ratios of 25:1 and 50:1 was significantly reduced in women with a history of endometriosis from that of the control group (26.6% versus 33.3% and 36.1% versus 43.3%, respectively, both P < 0.001). Furthermore, after further division of patients into three subgroups according to the location of endometriosis lesions, we observed that NK cytotoxicity in the endometriosis subgroups, especially the mixed endometriosis group, was strongly decreased from that of the controls (P = 0.001). The endometrial CD68+ macrophage proportion in the mixed endometriosis subgroup was higher than that in the control group (2.8% versus 2.1%, P = 0.043). In addition, the baseline estradiol (E2) level was weakly correlated with the percentage of endometrial macrophages (r = 0.251, P = 0.009), indicating a potential association among the endocrine system, endometrial immune environment, and endometriosis. This study indicated that peripheral NK cytotoxicity and endometrial immune cell profiles could be useful for diagnosing and treating endometriosis and endometriosis-related reproductive diseases.

A Pilot Study on the Co-existence of Diabetes and Endometriosis in Reproductive-Age Women: Potential for Endometriosis Progression

“…Macrophage infiltration of ovarian endometriomas has been previously reported [ 24 ]. Furthermore, we have shown in a mouse model of endometriosis that progression of ENDO in ectopic lesions with high fat diet was associated with increased localization of macrophages in stromal cells as measured by F/480 immunostaning [ 25 ].…”

Endometrial proteomic profile of patients with repeated implantation failure

“…These patients included 22 females with a history of RIF who experienced failed pregnancy in the next period after endometrial scratch and 19 fertile females who retrieved successful pregnancy in the next period after endometrial scratch. Herein, RIF was defined as women who experienced two or more retrieval cycles and transferred more than ten high-quality embryos without pregnancy ( 29 ). Among these patients, endometria from six RIF patients and six controls were subjected to proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ).…”

An Estrogen–NK Cells Regulatory Axis in Endometriosis, Related Infertility, and Miscarriage

“…Although there are different results regarding changes in the number of peripheral NK cells in endometriosis, it is unanimously agreed that peripheral NK cells have strong cytotoxicity; however, this effect is weakened in endometriosis. Research has shown that peripheral NK cytotoxicity is significantly decreased in endometriosis patients [ 32 ]. Oosterlynck et al observed a decrease in the cytotoxic activity of peripheral NK cells in patients with stage I/II endometriosis as the disease progressed.…”