Hypothetical roadmap towards endometriosis: prenatal endocrine-disrupting chemical pollutant exposure, anogenital distance, gut-genital microbiota and subclinical infections

Abstract BACKGROUND Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ~10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes infertility in ~30% of affected women. Despite intense research on the mechanisms involved in the initial development and later progression of endometriosis, many questions remain unanswered and its aetiology remains unknown. Recent studies have demonstrated the critical role played by the relationship between the microbiome and mucosal immunology in preventing sexually transmitted diseases (HIV), infertility and several gynaecologic diseases. OBJECTIVE AND RATIONALE In this review, we sought to respond to the main research question related to the aetiology of endometriosis. We provide a model pointing out several risk factors that could explain the development of endometriosis. The hypothesis arises from bringing together current findings from large distinct areas, linking high prenatal exposure to environmental endocrine-disrupting chemicals with a short anogenital distance, female genital tract contamination with the faecal microbiota and the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. SEARCH METHODS We performed a search of the scientific literature published until 2019 in the PubMed database. The search strategy included the following keywords in various combinations: endometriosis, anogenital distance, chemical pollutants, endocrine-disrupting chemicals, prenatal exposure to endocrine-disrupting chemicals, the microbiome of the female reproductive tract, microbiota and genital tract, bacterial vaginosis, endometritis, oestrogens and microbiota and microbiota–immune system interactions. OUTCOMES On searching the corresponding bibliography, we found frequent associations between environmental endocrine-disrupting chemicals and endometriosis risk. Likewise, recent evidence and hypotheses have suggested the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. Hence, we can envisa