Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action

Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features fibrotic adhesions caused by periodic bleeding. The characteristic ectopic lesions are marked by a widely spread dense fibrotic interstitium comprising of fibroblasts, myofibroblasts, collagen fibers, extracellular proteins, inflammatory cells, and active angiogenesis. Fibrosis is now recognized as a critical component of endometriosis because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or noncyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root causes, etiology, and complex pathogenesis of this debilitating condition, hinders early diagnosis and implement effective therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Emerging research offer a close relationship between endometriosis and fibrosis, which is believed to be tightly linked to pain, a primary contributor to the deterioration of the patient's quality of life. However, the underlying pathophysiological cellular and molecular signaling pathways behind endometriosis-associated fibrosis are poorly addressed. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease limiting the treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article focuses on recent developments in the field and highlight the necessity for novel fibrotic models for early diagnosis, a better understanding the disease's etiology and develop effective anti-fibrotic treatments. By addressing these knowledge gaps, we want to open fresh avenues for a thorough investigation and extended research in the field of endometriosis.