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      Menstruation: science and society

      review-article
      , MD a , , , MD b , , MD b , , MPA c , , MS d , e , , MD f , , MBBCh, BAO g , , PhD h , , MBA i , , MD, MSCI j , , MD, MPH k , , PhD a , , PhD f , , PhD d , , PhD l , , DrPH, MSN m , , MD, PhD d , e , n , o , , MBA, SM p , , MD q , , PhD r , s , , PhD t
      American Journal of Obstetrics and Gynecology
      Elsevier
      abnormal uterine bleeding, adenomyosis, endometrium, fibroids, menstrual health, microbiome, pelvic health menstrual effluent, period poverty, stem cells, tissue engineering, uterus

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          Abstract

          Women’s health concerns are generally underrepresented in basic and translational research, but reproductive health in particular has been hampered by a lack of understanding of basic uterine and menstrual physiology. Menstrual health is an integral part of overall health because between menarche and menopause, most women menstruate. Yet for tens of millions of women around the world, menstruation regularly and often catastrophically disrupts their physical, mental, and social well-being. Enhancing our understanding of the underlying phenomena involved in menstruation, abnormal uterine bleeding, and other menstruation-related disorders will move us closer to the goal of personalized care. Furthermore, a deeper mechanistic understanding of menstruation—a fast, scarless healing process in healthy individuals—will likely yield insights into a myriad of other diseases involving regulation of vascular function locally and systemically. We also recognize that many women now delay pregnancy and that there is an increasing desire for fertility and uterine preservation. In September 2018, the Gynecologic Health and Disease Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a 2-day meeting, “Menstruation: Science and Society” with an aim to “identify gaps and opportunities in menstruation science and to raise awareness of the need for more research in this field.” Experts in fields ranging from the evolutionary role of menstruation to basic endometrial biology (including omic analysis of the endometrium, stem cells and tissue engineering of the endometrium, endometrial microbiome, and abnormal uterine bleeding and fibroids) and translational medicine (imaging and sampling modalities, patient-focused analysis of menstrual disorders including abnormal uterine bleeding, smart technologies or applications and mobile health platforms) to societal challenges in health literacy and dissemination frameworks across different economic and cultural landscapes shared current state-of-the-art and future vision, incorporating the patient voice at the launch of the meeting. Here, we provide an enhanced meeting report with extensive up-to-date (as of submission) context, capturing the spectrum from how the basic processes of menstruation commence in response to progesterone withdrawal, through the role of tissue-resident and circulating stem and progenitor cells in monthly regeneration—and current gaps in knowledge on how dysregulation leads to abnormal uterine bleeding and other menstruation-related disorders such as adenomyosis, endometriosis, and fibroids—to the clinical challenges in diagnostics, treatment, and patient and societal education. We conclude with an overview of how the global agenda concerning menstruation, and specifically menstrual health and hygiene, are gaining momentum, ranging from increasing investment in addressing menstruation-related barriers facing girls in schools in low- to middle-income countries to the more recent “menstrual equity” and “period poverty” movements spreading across high-income countries.

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          Most cited references389

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          Structure, Function and Diversity of the Healthy Human Microbiome

          Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology, and translational applications of the human microbiome.
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            Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.

            The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5(+) stem cells can also initiate these cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
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              Integrated Genomic Characterization of Endometrial Carcinoma

              Summary We performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and ~25% of high-grade endometrioid tumors have extensive copy number alterations, few DNA methylation changes, low ER/PR levels, and frequent TP53 mutations. Most endometrioid tumors have few copy number alterations or TP53 mutations but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in the SWI/SNF gene ARID5B. A subset of endometrioid tumors we identified had a dramatically increased transversion mutation frequency, and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may impact post-surgical adjuvant treatment for women with aggressive tumors.
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                Author and article information

                Contributors
                Journal
                Am J Obstet Gynecol
                Am J Obstet Gynecol
                American Journal of Obstetrics and Gynecology
                Elsevier
                0002-9378
                1097-6868
                1 November 2020
                November 2020
                : 223
                : 5
                : 624-664
                Affiliations
                [a ]Medical Research Council Centre for Reproductive Health, The University of Edinburgh, United Kingdom
                [b ]Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL
                [c ]Days for Girls, Mt. Vernon, WA
                [d ]Igenomix Foundation-Instituto de Investigación Sanitaria Hospital Clínico, INCLIVA, Valencia, Spain
                [e ]Department of Pediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain
                [f ]The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY
                [g ]Massachusetts General Hospital, Boston, MA
                [h ]Feinberg School of Medicine, Northwestern University, Chicago, IL
                [i ]Below your Belt Health, Chicago, IL
                [j ]Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI
                [k ]Division of Research, Department of Obstetrics and Gynecology, Women and Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI
                [l ]Department of Communication, University of Delaware, Newark, DE
                [m ]Department of Sociomedical Sciences, Columbia University Mailman School of Public Health, New York, NY
                [n ]Beth Israel Deaconess Medical Center, Harvard University, Boston, MA
                [o ]Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX
                [p ]NextGen Jane, Oakland, CA
                [q ]Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT
                [r ]Department of Ecology and Evolutionary Biology, Department of Obstetrics, Gynecology and Reproductive Sciences, Systems Biology Institute, Yale University, New Haven, CT
                [s ]Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI
                [t ]Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, MA
                Author notes
                []Corresponding author: Hilary O.D. Critchley, MD. hilary.critchley@ 123456ed.ac.uk
                Article
                S0002-9378(20)30619-0
                10.1016/j.ajog.2020.06.004
                7661839
                32707266
                b404766a-ab6a-4a1a-b845-8e22f9262980
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 20 March 2020
                : 13 May 2020
                : 3 June 2020
                Categories
                Expert Reviews

                Obstetrics & Gynecology
                abnormal uterine bleeding,adenomyosis,endometrium,fibroids,menstrual health,microbiome,pelvic health menstrual effluent,period poverty,stem cells,tissue engineering,uterus

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