{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:27:08Z","timestamp":1790803628728,"version":"4.1.0"},"reference-count":48,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["216362\/Z\/19\/Z"],"award-info":[{"award-number":["216362\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["209328\/Z\/17\/Z"],"award-info":[{"award-number":["209328\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["MR\/R006237\/1"],"award-info":[{"award-number":["MR\/R006237\/1"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["MR\/X008304\/1"],"award-info":[{"award-number":["MR\/X008304\/1"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["226202\/Z\/22\/Z"],"award-info":[{"award-number":["226202\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020643","name":"MRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020643","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Turner syndrome (TS) is the most common genetic cause of premature (primary) ovarian insufficiency (POI). Human fetal 45,X ovaries demonstrate marked apoptosis by 15 to 20 weeks post conception (wpc), likely partly driven by X-chromosome haploinsufficiency. However, the genomic drivers of ovarian insufficiency in TS remain largely unexplored.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We used single-nuclei sequencing (snRNA-seq) and bulk RNA sequencing (RNA-seq) technologies to profile the transcriptome of ovarian insufficiency in TS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using snRNA-seq, we profiled 2 perimeiotic 46,XX and 2 45,X (TS) human fetal ovaries (12-13 wpc). Using bulk RNA-seq, we conducted a time-series analysis of human fetal tissue across 4 developmental time points (19 fetal ovary, 20 fetal testis, 8 fetal control tissue (n = 47 total samples; Carnegie stage 22-16 wpc)).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Germ and somatic cell subpopulations were mostly shared across 46,XX and 45,X ovaries, aside from an oogonia cluster depleted in 45,X ovaries containing genes with functions relating to sex chromosome synapsis. snRNA-seq enabled accurate cell counting across individual cell clusters and revealed that the 45,X ovary has fewer germ cells than the 46,XX ovary in every germ cell subpopulation, confirmed by histopathological analysis. The normal sequence of X-chromosome inactivation and reactivation is disrupted in 45,X ovaries. The 45,X ovary has a globally abnormal transcriptome, with lower expression of genes with proteostasis functions (RSP4X); cell cycle progression (BUB1B); and OXPHOS energy production (COX6C, ATP11C).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>We characterize the human fetal perimeiotic 45,X ovary at single-cell resolution and offer insights into the genomic mechanisms of the ovarian insufficiency phenotype in TS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvaf094","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T07:47:36Z","timestamp":1748504856000},"source":"Crossref","is-referenced-by-count":1,"title":["Characterizing the Human Fetal Perimeiotic 45,X Ovary at Single-Cell 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Institute of Child Health, University College London , London WC1N 1EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Crespo","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London , London WC1N 1EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olumide K","family":"Ogunbiyi","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London , London WC1N 1EH ,","place":["UK"]},{"name":"Department of Histopathology, Great Ormond Street Hospital for Children National Health Service (NHS) Foundation Trust , London WC1N 3JH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Niola","sequence":"additional","affiliation":[{"name":"UCL Genomics, Zayed Centre for Research, UCL Great Ormond Street Institute of Child Health, University College London , London WC1N 1DZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Brooks","sequence":"additional","affiliation":[{"name":"UCL Genomics, Zayed Centre for Research, UCL Great Ormond Street Institute of Child Health, University College London , London WC1N 1DZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nita","family":"Solanky","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London , London WC1N 1EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard 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