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 envisage a direct relationship between higher prenatal exposure to oestrogens or estrogenic endocrine-disrupting compounds (phthalates, bisphenols, organochlorine pesticides and others) and a shorter anogenital distance, which could favour frequent postnatal episodes of faecal microbiota contamination of the vulva and vagina, producing cervicovaginal microbiota dysbiosis. This relationship would disrupt local antimicrobial defences, subverting the homeostasis state and inducing a subclinical inflammatory response that could evolve into a sustained immune dysregulation, closing the vicious cycle responsible for the development of endometriosis. WIDER IMPLICATIONS Determining the aetiology of endometriosis is a challenging issue. Posing a new hypothesis on this subject provides the initial tool necessary to design future experimental, clinical and epidemiological research that could allow for a better understanding of the origin of this disease. Furthermore, advances in the understanding of its aetiology would allow the identification of new therapeutics and preventive actions.

中文翻译：

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子宫内膜异位症的假想路线图：产前破坏内分泌的化学污染物暴露，肛门生殖器距离，肠道生殖器微生物群和亚临床感染。

背景技术子宫内膜异位症是一种妇科激素依赖性疾病，其定义为子宫内膜样组织从子宫腔外生长而产生的组织学损伤，子宫内膜样组织最常植入腹膜腔内，尽管这些损伤也可以位于远处的器官中。子宫内膜异位症影响约10％的育龄妇女，经常产生严重的，有时甚至是失能的症状，包括慢性骨盆痛，痛经和痛经。此外，子宫内膜异位症在约30％的受影响女性中引起不孕。尽管对子宫内膜异位症的初始发展和后来发展的机制进行了深入研究，但许多问题仍未得到解答，其病因仍未知。最近的研究表明，微生物组和粘膜免疫学之间的关系在预防性传播疾病（HIV），不育症和几种妇科疾病中起着至关重要的作用。目的和理由在本综述中，我们试图回答与子宫内膜异位症病因相关的主要研究问题。我们提供了一个模型，指出了一些可以解释子宫内膜异位症发展的风险因素。该假说来自于将来自不同地区的最新发现汇总在一起，将产前大量暴露于环境中的内分泌干扰化学物质与较短的肛门生殖器距离，女性生殖道被粪便微生物群污染以及生殖器亚临床微生物感染在发育中的积极作用联系在一起。子宫内膜异位症的临床进展。搜索方法我们对PubMed数据库中直到2019年为止发表的科学文献进行了搜索。搜索策略包括以下各种组合的关键字：子宫内膜异位，肛门生殖器距离，化学污染物，破坏内分泌的化学物质，产前接触破坏内分泌的化学物质，女性生殖道，微生物群和生殖道的微生物组，细菌性阴道病，子宫内膜炎，雌激素与微生物群和微生物群-免疫系统的相互作用。结果在搜索相应的书目时，我们发现破坏环境内分泌的化学物质与子宫内膜异位症风险之间的频繁关联。同样，最近的证据和假设表明，生殖器亚临床微生物感染在子宫内膜异位症的发展和临床进程中起着积极作用。因此，我们可以设想，产前暴露于雌激素或破坏雌激素的内分泌化合物（邻苯二甲酸酯，双酚，有机氯农药等）的直接暴露与较短的肛门生殖距离之间存在直接关系，这可能有利于产后频繁发生粪便对外阴部微生物的污染。阴道，产生宫颈阴道菌群失调。这种关系将破坏局部抗菌素防御，破坏体内平衡​​状态，并诱发亚临床炎症反应，可能演变为持续的免疫失调，从而结束导致子宫内膜异位症发展的恶性循环。进一步的含义确定子宫内膜异位的病因是一个具有挑战性的问题。在这个问题上提出新的假设可为设计未来的实验提供必要的初始工具，临床和流行病学研究，可以更好地了解这种疾病的起源。此外，对其病因学的理解的进步将允许鉴定新的疗法和预防措施。