Evaluation of Evaluate M1 and M2 Macrophages in Endometriotic Tissue of Women Affected by Endometriosis at Different Stages.

Background and rationale: Endometriosis is an estrogen-dependent disease defined by the ectopic presence and growth of functional endometrial tissue, glands and stroma, outside the uterine cavity (Kavoussi et al, 2016). The aetiopathogenesis of endometriosis still remains controversial: immune, hormonal, genetic, and epigenetic factors may be all involved, and several theories have been proposed to explain it.

The disease affects 2-10 % of women of reproductive age and 50 % of those infertile (Dunselman et al, 2014) and may cause pelvic pain (Triolo et al, 2013; Butticè et al, 2013), abnormal bleeding, infertility/sterility and, consequently, important psychological problems (Laganà et al, 2015). Endometriosis is classified depending on the number, size, and superficial and/or deep location of endometrial implants, plaques, endometriomas and/or adhesions. The most used classification of endometriosis was developed by the American Society for Reproductive Medicine (Rock JA, 1995), although other classification can be used for deep infiltrating endometriosis (Haas et al, 2011) or to correlate endometriosis and infertility (Adamson et al, 2010).

As widely evidenced (Donnez et al, 2016), it is generally accepted that moderate/severe endometriosis-related sterility is due to mechanical factors, namely to the distortion/subversion of the regular pelvic anatomy. On the contrary, the factors behind infertility/subfertility related to minimal/mild endometriosis are less clear. Nevertheless, to date none of the hypothesized mechanisms exhaustively explained the infertility related to endometriosis, while it is possible that such disease is caused by multiple factors altogether, including genetic and epigenetic modifications (Sofo et al, 2015; Maniglio et al, 2016).

Accumulating evidence (Laganà et al, 2013; Laganà et al, 2016) suggests that the peritoneal microenvironment of women affected by endometriosis undergoes a number of local inflammatory-reparative phenomena, with the involvement of resident macrophages, and the attraction and recruitment of peripheral mononuclear cells (monocytes and lymphocytes) from the blood into the peritoneal cavity: during endometriosis a breakdown occurs in endometrial and peritoneal homeostasis caused by cytokine-addressed cell proliferation (Pizzo et al, 2002) and dysregulation of apoptosis (Sturlese et al, 2011; Salmeri et al, 2015).

Monocytes play a key role during adaptive immunity, since they migrates in sites of infection or inflammation, differentiate in macrophages and act as Antigene Presenting Cells (APCs).