Alterations in expression of endometrial milk fat globule-EGF factor 8 (MFG-E8) and leukemia inhibitory factor (LIF) in patients with infertility and endometriosis

Abstract

ObjectiveThe aim of this study was to compare the endometrial expression of milk fat globule-EGF factor 8 (MFG-E8), its receptor integrin αvβ3, and leukemia inhibitory factor (LIF) in patients with endometriosis and infertility and in healthy fertile patients during the window of implantation.MethodsFive patients with peritoneal endometriosis and infertility (case group) and four healthy fertile patients (control group) were recruited. All patients were either diagnosed with or ruled out for endometriosis by laparoscopic surgery; the case group underwent surgery for infertility investigation and the control group for tubal ligation. Endometrial biopsies were performed in all patients during the window of implantation (LH+8 to LH+10), and then the samples were analyzed by immunochemistry for MFG-E8, integrin αvβ3, and LIF.ResultsIn patients with endometriosis and infertility, expression of MFG-E8 was significantly increased in the glandular epithelium when compared to healthy fertile patients (p<0.001). Moreover, LIF expression was lower in patients with endometriosis and infertility (p<0.05). Nevertheless, we found no difference in integrin αvβ3 expression between the groups (p=0.084).ConclusionThis study showed for the first time that MFG-E8 expression is impaired in the endometrium of patients with endometriosis and infertility during the window of implantation. Moreover, LIF is also diminished in the endometrium of these patients as shown before.

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis

“…Among altered cytokines, leukemia inhibitory factor (LIF), a member of IL-6-like family E2-responsive, essential for blastocyst implantation, also shows reduced expression in infertile patients with endometriosis, especially at moderate stages of the disease (160,161). Another IL-6-like family member required for embryo implantation, IL-11, and its receptor, are absent in the glandular epithelium of endometrium from endometriosis patients, in contrast to fertile women (161).…”

Regulation mechanism of miR-494-3p on endometrial receptivity in mice via PI3K/AKT/mTOR pathway

“…LIF plays a role in the adhesion and infiltration stages of implantation (Dimitriadis et al 2010). Moreover, LIF was a key factor in the regulation of embryo implantation (Schmitz et al 2017). VEGF receptor 2 (VEGFR-2) was considered to be the most important VEGF receptor during angiogenesis and was known to regulate endometrial angiogenesis (Waltenberger et al 1994).…”

“…LIF, Ang-2 and VEGF, thus improving embryo implantation (Schmitz et al 2017) and maintaining pregnancy (Fiorimanti et al 2018) to improve endometrial receptivity and promote embryo implantation (Segal et al 2020). Interestingly, VEGF attenuated the HIF-1α signaling reducing resistance to antiangiogenic therapy (Tsai et al 2016).…”

“…Downregulated LIF expression is associated with implantation defects in female infertility. In many mammals, including humans, LIF expression is significantly increased during implantation, indicating that LIF is a key factor in the regulation of implantation (Schmitz et al 2017). Besides, angiopoietin-2 (Ang-2) is involved in villi formation during implantation and the establishment of fetal and maternal capillary network, which is very important for maintaining pregnancy (Fiorimanti et al 2018).…”

Etiopathogenesis of endometriosis-associated infertility (a review)

“…Исследования [21,22] показывают снижение экспрессии интегрина αVβ3, который принимает участие в первоначальном прикреплении эмбриона, а также остеопонтина, LIF и его рецепторов LIFR и gp130 на поверхности бластоцисты, повышение активности металлопротеиназ и гликопротеина MFG-E8, экспрессии NF-kB, Bcl-2.…”