The role of TGF-β in the pathophysiology of peritoneal endometriosis

BACKGROUND: Endometriosis is estimated to affect 6-10% of women of reproductive age and it is associated with chronic pelvic pain, dysmenorrhoea and subfertility. It is currently managed surgically or medically but symptoms recur in up to 75% of cases and available medical treatments have undesirable side effects. Endometriosis is defined as the presence of endometrial tissue outside the uterus with lesions typically found on the peritoneum. The aetiology of endometriosis is uncertain but there is increasing evidence that transforming growth factor (TGF)-beta plays a major role. OBJECTIVE AND RATIONALE: A descriptive review was undertaken of the published literature on the expression pattern of TGF-beta ligands and signalling molecules in women with and without endometriosis, and on the potential roles of TGF-beta signalling in the development and progression of peritoneal endometriosis. The current understanding of the TGF-beta signalling pathway is summarized. SEARCH METHODS: We searched the Pubmed database using the terms ` transforming growth factor beta' and ` endometriosis' for studies published between 1995 and 2016. The initial search identified 99 studies and these were used as the basic material for this review. We also extended our remit for important older publications. In addition, we searched the reference lists of studies used in this review for additional studies we judged as relevant. Studies which were included in the review focused on peritoneal endometriosis only as increasing evidence suggests that ovarian and deep endometriosis may have a differing pathophysiology. Thus, a final 95 studies were included in the review. OUTCOMES: TGF-beta 1 is reported to be increased in the peritoneal fluid, serum, ectopic endometrium and peritoneum of women with endometriosis compared to women without endometriosis, and TGF-beta 1-null mice have reduced endometriosis lesion growth when compared to their wild-type controls. Studies in mice and women have indicated that increasing levels of TGF-beta ligands are associated with decreased immune cell activity within the peritoneum, together with an increase in ectopic endometrial cell survival, attachment, invasion and proliferation, during endometriosis lesion development. TGF-beta 1 has been associated with changes in ectopic endometrial and peritoneal cell metabolism and the initiation of neoangiogenesis, further fuelling endometriosis lesion development. WIDER IMPLICATIONS: Together these studies suggest that TGF-beta 1 plays a major role in the development of peritoneal endometriosis lesions and that targeting this pathway may be of therapeutic potential.