Showing papers by "Anthony A. Luciano published in 2021"

Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues.

Abstract: Endometriosis is characterized by growth of endometrial-like tissue outside of the uterus affecting many women in their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, limiting diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared to matched eutopic endometrium, control endometrium, and organoids derived from these tissues, generating data on over 100,000 cells across 12 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell unique to the peritoneal lesions with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesions microenvironments, and a novel progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment representing the first comprehensive cell atlas of the disease, essential information for advancing therapeutics and diagnostics.

Medical management of endometriosis.

Abstract: Introduction Endometriosis is a benign gynecologic disorder that is defined as functional endometrial tissue outside of the uterine cavity. It is an estrogen-dependent, inflammatory disease that leads to symptoms of pelvic pain, dysmenorrhea, dyspareunia, and infertility, occurring in 6-10% of reproductive aged women. The severity of the disease ranges from asymptomatic to debilitating symptoms that have a major impact on women's lives. It is a chronic, recurrent disease, frequently requiring long term management until menopause and beyond. It is considered a chronic disorder that is managed with surgery, medical treatment, and oftentimes, both. Current medical therapy for endometriosis is considered suppressive of the disease, rather than curative. Fortunately, many patients do experience improvement and control of their symptoms with medical therapy. However, long-term efficacy of the medical treatments is often limited by side effects and the cost of therapy, and symptoms do tend to recur after discontinuation of these medications. Areas covered This review summarizes our understanding of the pathogenesis of endometriosis and provides more in-depth discussion of specific medical management options used to treat endometriosis, including mechanism of action and side effects. It also provides recommendations on strategy with a forward look to novel endometriosis treatments in the future. Expert opinion The authors emphasize that endometriosis is a chronic disorder requiring long term medical therapy. Early diagnosis of endometriosis is key in preventing severe, debilitating symptoms and progression of disease. By utilizing our current knowledge of the pathophysiology of endometriosis and by correctly implementing currently available medical and surgical therapies we can significantly reduce the physical, psychosocial and financial burden of this chronic, recurrent and indolent disease. Current available medications are suppressive therapies, but the authors are looking forward to future therapies that can effectively cure or at least control endometriosis with minimal side effects. Future research should continue to look for the genetic trigger for endometriosis which can lead us to its underlying pathogenesis and eventually a cure or prevention.