BCG vaccine and endometriosis: an hypothesis

Endometriosis currently affects approximately 10% of women worldwide. The causes of endometriosis remain poorly understood, yet effective treatment requires a thorough comprehension of the genesis of endometrial ectopic lesions and the factors contributing to their persistence. We propose that one of the causes of endometriosis results from a neonatal assault by the BCG vaccine administered at a time when the newborn's immune system is unable to mount an adequate response. This impaired control is attributable to the lingering presence of HLA-G-a key immunoregulatory molecule responsible for maternal-fetal immune tolerance during pregnancy-which requires approximately one week to be fully cleared from the newborn's bloodstream. A second necessary condition involves the presence of a fully functional endometrium at birth, a phenomenon observed in many female neonates. The severity of endometriosis manifestation will vary depending on the genetic characteristics of the patient's immune system, the conditions prevailing during embryogenesis, and lifestyle factors. Our novel hypothesis incorporates all seven previously proposed theories regarding the origins of endometriosis. It also accounts for rare cases of male endometriosis, as well as spontaneous endometriosis (without BCG vaccination) reported in chimpanzees. This hypothesis could be readily tested since it offers predictions focussed on the temporal, spatial, immunological, and functional aspects. Seven different tests of the model are proposed, leveraging existing cohorts, registries, and experimental designs. If validated, this hypothesis would not only provide a unifying mechanistic framework for endometriosis but also shift prevention strategies-reconsidering the timing of neonatal BCG. Identifying the origins of endometriosis opens the door to targeted causal interventions, potentially transforming the management of the disease from symptomatic relief to curative approaches.