Mapping the anatomical and transcriptional landscape of early human fetal ovary development
Abstract The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary (or Premature) Ovarian Insufficiency and Differences of Sex Development. We combine single-nuclei RNA sequencing, bulk RNA sequencing, and micro-focus compute...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-96135-y |
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| author | Sinead M. McGlacken-Byrne Ignacio del Valle Theodoros Xenakis Ian C. Simcock Jenifer P. Suntharalingham Federica Buonocore Berta Crespo Nadjeda Moreno Danielle Liptrot Paola Niola Tony Brooks Gerard S. Conway Mehul T. Dattani Owen J. Arthurs Nita Solanky John C. Achermann |
| author_facet | Sinead M. McGlacken-Byrne Ignacio del Valle Theodoros Xenakis Ian C. Simcock Jenifer P. Suntharalingham Federica Buonocore Berta Crespo Nadjeda Moreno Danielle Liptrot Paola Niola Tony Brooks Gerard S. Conway Mehul T. Dattani Owen J. Arthurs Nita Solanky John C. Achermann |
| author_sort | Sinead M. McGlacken-Byrne |
| collection | DOAJ |
| description | Abstract The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary (or Premature) Ovarian Insufficiency and Differences of Sex Development. We combine single-nuclei RNA sequencing, bulk RNA sequencing, and micro-focus computed tomography to elucidate the anatomy and transcriptional landscape of the human fetal ovary across key developmental timepoints (Carnegie Stage 22 until 20 weeks post conception). We show the marked growth and distinct morphological changes within the fetal ovary at the critical timepoint of germ cell expansion and demonstrate that the fetal ovary becomes more transcriptomically distinct from the testis with age. We describe previously uncharacterised ovary developmental pathways, relating to neuroendocrine signalling, energy homeostasis, mitochondrial networks, and inflammasome regulation. We define transcriptional regulators and candidate genes for meiosis within the developing ovary. Together, this work advances our fundamental understanding of human ovary development and has relevance for human ovarian insufficiency phenotypes. |
| format | Article |
| id | doaj-art-36b4e8deea834a8a8f24c7e0da97ada7 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-36b4e8deea834a8a8f24c7e0da97ada72025-08-20T02:15:02ZengNature PortfolioScientific Reports2045-23222025-05-0115112010.1038/s41598-025-96135-yMapping the anatomical and transcriptional landscape of early human fetal ovary developmentSinead M. McGlacken-Byrne0Ignacio del Valle1Theodoros Xenakis2Ian C. Simcock3Jenifer P. Suntharalingham4Federica Buonocore5Berta Crespo6Nadjeda Moreno7Danielle Liptrot8Paola Niola9Tony Brooks10Gerard S. Conway11Mehul T. Dattani12Owen J. Arthurs13Nita Solanky14John C. Achermann15Genetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonDepartment of Clinical Radiology, Great Ormond Street Hospital for Children NHS Foundation TrustGenetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonUCL Genomics, Zayed Centre for Research, UCL Great Ormond Street Institute of Child Health, University College LondonUCL Genomics, Zayed Centre for Research, UCL Great Ormond Street Institute of Child Health, University College LondonInstitute for Women’s Health, University College LondonGenetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonDepartment of Clinical Radiology, Great Ormond Street Hospital for Children NHS Foundation TrustDevelopmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College LondonAbstract The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary (or Premature) Ovarian Insufficiency and Differences of Sex Development. We combine single-nuclei RNA sequencing, bulk RNA sequencing, and micro-focus computed tomography to elucidate the anatomy and transcriptional landscape of the human fetal ovary across key developmental timepoints (Carnegie Stage 22 until 20 weeks post conception). We show the marked growth and distinct morphological changes within the fetal ovary at the critical timepoint of germ cell expansion and demonstrate that the fetal ovary becomes more transcriptomically distinct from the testis with age. We describe previously uncharacterised ovary developmental pathways, relating to neuroendocrine signalling, energy homeostasis, mitochondrial networks, and inflammasome regulation. We define transcriptional regulators and candidate genes for meiosis within the developing ovary. Together, this work advances our fundamental understanding of human ovary development and has relevance for human ovarian insufficiency phenotypes.https://doi.org/10.1038/s41598-025-96135-yOvary developmentOvary functionOvarian insufficiencyTranscriptomicsMicro-focus computed tomography |
| spellingShingle | Sinead M. McGlacken-Byrne Ignacio del Valle Theodoros Xenakis Ian C. Simcock Jenifer P. Suntharalingham Federica Buonocore Berta Crespo Nadjeda Moreno Danielle Liptrot Paola Niola Tony Brooks Gerard S. Conway Mehul T. Dattani Owen J. Arthurs Nita Solanky John C. Achermann Mapping the anatomical and transcriptional landscape of early human fetal ovary development Scientific Reports Ovary development Ovary function Ovarian insufficiency Transcriptomics Micro-focus computed tomography |
| title | Mapping the anatomical and transcriptional landscape of early human fetal ovary development |
| title_full | Mapping the anatomical and transcriptional landscape of early human fetal ovary development |
| title_fullStr | Mapping the anatomical and transcriptional landscape of early human fetal ovary development |
| title_full_unstemmed | Mapping the anatomical and transcriptional landscape of early human fetal ovary development |
| title_short | Mapping the anatomical and transcriptional landscape of early human fetal ovary development |
| title_sort | mapping the anatomical and transcriptional landscape of early human fetal ovary development |
| topic | Ovary development Ovary function Ovarian insufficiency Transcriptomics Micro-focus computed tomography |
| url | https://doi.org/10.1038/s41598-025-96135-y |
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