Hydrosalpinx perturbs the tubal and endometrial immune environment

Abstract: Hydrosalpinx is a chronic pathological manifestation seen in approximately 30% of tubal disease cases. In addition to contributing to infertility and pelvic pain, hydrosalpinx has been associated with early pregnancy loss and reduced implantation in assisted reproductive technology. Though not fully understood, previous studies have demonstrated altered immunological activity in those with hydrosalpinx, which has been suggested to impact endometrial receptivity. To validate these findings and to explore the pathogenesis of tubal disease, the aim of this study was to identify and quantify the immune cell population in tubes with hydrosalpinx and endometrium from the same patients. This observational study included patients in the secretory phase of the menstrual cycle undergoing salpingectomy/salpingo-oophorectomy with/without hysterectomy for benign gynaecological conditions. The number and type of immune cells present in endometrial and fallopian tube tissue sections were investigated using immunostaining for CD45, CD3, CD4, CD8, CD56 and CD68. We show that T cells are more abundant in the endometrium of women with hydrosalpinx and that cytotoxic T cell numbers are lower in diseased tubes. Uterine natural killer cells and macrophages are significantly elevated in both tubal and endometrial tissue in hydrosalpinx, demonstrating a disruption in the normal uterine immune cell microenvironment that may affect endometrial receptivity, with implications for tubal disease-associated subfertility. Lay summary: Hydrosalpinx is a common condition characterised by inflammation, distortion and fluid accumulation in the fallopian tube. Hydrosalpinx is a leading cause of subfertility, however, the mechanisms that cause this problem are not fully understood. We studied the immune cells present in both the fallopian tubes and uterine lining (endometrium) of women with hydrosalpinx and compared them to samples from women without tubal disease. The samples were collected in the second half of the menstrual cycle, when the uterine lining is prepared for implantation of a fertilised embryo. We quantified the total immune cell numbers and specific immune cell subtypes (these are immune cells with specific roles in the body, such as destroying harmful bacteria or regulating the immune system) in the different tissues and compared them between the hydrosalpinx and control groups. We found that hydrosalpinx is associated with both tubal and endometrial immune cell changes, which may contribute to infertility by affecting the normal physiological processes that allow the endometrium to accept an embryo and establish a pregnancy.