The pathogenesis of endometriosis: clues from the immunological evidence

INTRODUCTION: Endometriosis pathogenesis is still a matter of debate. It is now agreed that a complex cooperation of genetic, hormonal, immune and environmental factors is implicated. However, no consensus has been reached yet on what firstly is responsible for the initiation, promotion and survival of endometrial-like tissue outside the uterine cavity. Since consistent evidence have found immunological alterations in women with the disease, the impairment of immune system has been considered for decades one of the possible causes of endometriosis. The aim of this literature review is to summarize the available findings on a particular aspect of this topic represented by the inhibition of natural killer (NK) cell activity in women affected as a paradigmatic example of the complexity in studying the pathogenesis of endometriosis. EVIDENCE ACQUISITION: Advanced search of PubMed for English articles published between 1990 and September 2020 using the keywords "endometriosis" or "endometrioma" or "endometriotic" or "ectopic endometrium" in combination with "natural killer cells" (NK). EVIDENCE SYNTHESIS: Consistent studies have found an impairment in NK cell activity in women with endometriosis especially in advanced stages of disease (stage III/IV). Reports to explain these findings support the phenomenon as a consequence of the disease establishment. Evidence from genetic studies have questioned the role of these dysfunctions in the pathogenesis of the disease. CONCLUSIONS: Immunological dysfunctions and the decreased NK cell cytotoxicity may only represent consequence of endometriosis, although the underlining mechanisms still need to be elucidated.