Peritoneal Macrophages From Patients With Endometriosis Release Growth Factor Activityin Vitro*

Abstract

We studied the in vitro secretion of macrophage-derived growth factor (MDGF) activity by peritoneal macrophages from fertile and infertile women. Peritoneal fluid was obtained from 55 women undergoing laparoscopy for evaluation and treatment of infertility or for tubal sterilization. Isolated macrophages were plated in tissue culture wells and incubated in Dulbecco's Modified Eagle's Medium plus 0.2% lactalbumin hydrolyzate at 37 C for 24 h. Medium MDGF activity was assayed by determining the ability of medium to stimulate [3H] thymidine incorporation in BALB-c 3T3 fibroblasts. Macrophages from 23 women released significant MDGF activity in vitro; the release was linear for up to 72 h. Among the 55 women, macrophages from 10 of 36 (28%) women with normal pelvic anatomy or tubal occlusion/pelvic adhesions released significant MDGF activity. In contrast, macrophages from 13 of 19 (68%) women with endometriosis, a significantly higher proportion (P less than 0.02), released MDGF. The finding that endometriosis is associated with in vivo primed peritoneal macrophages that produce MDGF in vitro may help to explain the proliferation or maintenance of endometrial tissue in the peritoneal cavity.

Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice

“…Factors other than sex steroid hormones probably play a key role in the growth and spreading of endometriosis. Local growth factors could regulate cell proliferation through autocrine or paracrine interactions (25,26).…”

“…Nine different human samples have been used. Endometrial samples obtained throughout the menstrual cycle gave rise to similar results (five were in the proliferative phase, days 4-13, and four were in the secretory phase, days [16][17][18][19][20][21][22][23][24][25][26]. Approval for this study was obtained from the Institutional Review Board of the University of Liège (Liège, Belgium).…”

Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium

“…Sampson's (1927) theory of transplantation of endometrial tissue on the pelvic peritoneum via retrograde menstruation is one of the most widely recognized explanations for the development of pelvic endometriosis. Retrograde menstruation is observed in nearly all cyclic women, and endometriosis is considered to develop as a result of the coexistence of a defect in clearance of the menstrual efflux from the pelvic peritoneal surfaces (Halme et al, 1988).…”

“…For example, the high concentrations of PGE 2 present in uterine carcinomas and endometriotic tissues may inhibit B-and T-cell proliferation and accessory monocyte-macrophage function, thereby allowing defective cells to proliferate undetected by the immune system (DeWitt, 1991). Cytokines such as IL-1 are known to induce COX-2 expression in vitro (Huang et al, 1998), and may act in a similar way in situ when secreted from immune cells and macrophages in endometriotic or neoplastic uterine tissues (Halme et al, 1988). This mechanism could augment COX-2 expression and PGE 2 biosynthesis and sustain immune evasion.…”

Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance

“…Sampson's theory of transplantation of endometrial tissue on the pelvic peritoneum via retrograde menstruation is the most widely accepted explanation for the development of pelvic endometriosis because of convincing circumstantial and experimental evidence (Sampson 1927). Since retrograde menstruation is observed in almost all cycling women, endometriosis is postulated to develop as a result of the coexistence of a defect in clearance of the menstrual efflux from pelvic peritoneal surfaces, possibly involving the immune system (Halme et al 1988). Alternatively, intrinsic molecular aberrations in pelvic endometriotic implants were proposed to contribute significantly to development of endometriosis.…”