Transcriptomic sex differences in early human fetal brain development
Abstract The influence of sex chromosomes and sex hormones on early human brain development is poorly understood. We therefore undertook transcriptomic analysis of 46,XY and 46,XX human brain cortex samples (n = 64) at four different time points between 7.5 and 17 weeks post conception (wpc), in two...
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08070-3 |
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| author | Federica Buonocore Jenifer P. Suntharalingham Olumide K. Ogunbiyi Aragorn Jones Nadjeda Moreno Paola Niola Tony Brooks Nita Solanky Mehul T. Dattani Ignacio del Valle John C. Achermann |
| author_facet | Federica Buonocore Jenifer P. Suntharalingham Olumide K. Ogunbiyi Aragorn Jones Nadjeda Moreno Paola Niola Tony Brooks Nita Solanky Mehul T. Dattani Ignacio del Valle John C. Achermann |
| author_sort | Federica Buonocore |
| collection | DOAJ |
| description | Abstract The influence of sex chromosomes and sex hormones on early human brain development is poorly understood. We therefore undertook transcriptomic analysis of 46,XY and 46,XX human brain cortex samples (n = 64) at four different time points between 7.5 and 17 weeks post conception (wpc), in two independent studies. This developmental period encompasses the onset of testicular testosterone secretion in the 46,XY fetus (8wpc). We show differences in sex chromosome gene expression including X-inactivation genes (XIST, TSIX) in 46,XX samples; core Y chromosome genes (n = 18) in 46,XY samples; and two Y chromosome brain specific genes, PCDH11Y and RP11-424G14.1. PCDH11Y (protocadherin11 Y-linked) regulates excitatory neurons; this gene is unique to humans and is implicated in language development. RP11-424G14.1 is a long non-coding RNA. Fewer differences in sex hormone pathway-related genes are seen. The androgen receptor (AR, NR3C4) shows cortex expression in both sexes, which decreases with age. Global cortical sex hormone effects are not seen, but more localized AR mechanisms may be important with time (e.g., hypothalamus). Taken together, our data suggest that limited but potentially important sex differences occur during early human fetal brain development. |
| format | Article |
| id | doaj-art-9e41601df03d4db7b6c7e7c0424b1ea9 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-9e41601df03d4db7b6c7e7c0424b1ea92025-08-20T02:28:42ZengNature PortfolioCommunications Biology2399-36422025-04-018111410.1038/s42003-025-08070-3Transcriptomic sex differences in early human fetal brain developmentFederica Buonocore0Jenifer P. Suntharalingham1Olumide K. Ogunbiyi2Aragorn Jones3Nadjeda Moreno4Paola Niola5Tony Brooks6Nita Solanky7Mehul T. Dattani8Ignacio del Valle9John C. Achermann10Genetics 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 Histopathology, Great Ormond Street Hospital for Children National Health Service (NHS) Foundation TrustBiosciences Institute, Faculty of Medical Sciences, Newcastle UniversityDevelopmental 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 LondonDevelopmental 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 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 LondonAbstract The influence of sex chromosomes and sex hormones on early human brain development is poorly understood. We therefore undertook transcriptomic analysis of 46,XY and 46,XX human brain cortex samples (n = 64) at four different time points between 7.5 and 17 weeks post conception (wpc), in two independent studies. This developmental period encompasses the onset of testicular testosterone secretion in the 46,XY fetus (8wpc). We show differences in sex chromosome gene expression including X-inactivation genes (XIST, TSIX) in 46,XX samples; core Y chromosome genes (n = 18) in 46,XY samples; and two Y chromosome brain specific genes, PCDH11Y and RP11-424G14.1. PCDH11Y (protocadherin11 Y-linked) regulates excitatory neurons; this gene is unique to humans and is implicated in language development. RP11-424G14.1 is a long non-coding RNA. Fewer differences in sex hormone pathway-related genes are seen. The androgen receptor (AR, NR3C4) shows cortex expression in both sexes, which decreases with age. Global cortical sex hormone effects are not seen, but more localized AR mechanisms may be important with time (e.g., hypothalamus). Taken together, our data suggest that limited but potentially important sex differences occur during early human fetal brain development.https://doi.org/10.1038/s42003-025-08070-3 |
| spellingShingle | Federica Buonocore Jenifer P. Suntharalingham Olumide K. Ogunbiyi Aragorn Jones Nadjeda Moreno Paola Niola Tony Brooks Nita Solanky Mehul T. Dattani Ignacio del Valle John C. Achermann Transcriptomic sex differences in early human fetal brain development Communications Biology |
| title | Transcriptomic sex differences in early human fetal brain development |
| title_full | Transcriptomic sex differences in early human fetal brain development |
| title_fullStr | Transcriptomic sex differences in early human fetal brain development |
| title_full_unstemmed | Transcriptomic sex differences in early human fetal brain development |
| title_short | Transcriptomic sex differences in early human fetal brain development |
| title_sort | transcriptomic sex differences in early human fetal brain development |
| url | https://doi.org/10.1038/s42003-025-08070-3 |
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