Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models
Sex-specific gonadal differentiation is initiated by the expression of SRY in male foetuses. This promotes a signalling pathway directing testicular development, while in female foetuses the absence of SRY and expression of pro-ovarian factors promote ovarian development. Importantly, in addition to...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.902082/full |
| _version_ | 1828200158724096000 |
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| author | Malene Lundgaard Riis Malene Lundgaard Riis Anne Jørgensen Anne Jørgensen |
| author_facet | Malene Lundgaard Riis Malene Lundgaard Riis Anne Jørgensen Anne Jørgensen |
| author_sort | Malene Lundgaard Riis |
| collection | DOAJ |
| description | Sex-specific gonadal differentiation is initiated by the expression of SRY in male foetuses. This promotes a signalling pathway directing testicular development, while in female foetuses the absence of SRY and expression of pro-ovarian factors promote ovarian development. Importantly, in addition to the initiation of a sex-specific signalling cascade the opposite pathway is simultaneously inhibited. The somatic cell populations within the gonads dictates this differentiation as well as the development of secondary sex characteristics via secretion of endocrine factors and steroid hormones. Opposing pathways SOX9/FGF9 (testis) and WNT4/RSPO1 (ovary) controls the development and differentiation of the bipotential mouse gonad and even though sex-specific gonadal differentiation is largely considered to be conserved between mice and humans, recent studies have identified several differences. Hence, the signalling pathways promoting early mouse gonad differentiation cannot be directly transferred to human development thus highlighting the importance of also examining this signalling in human fetal gonads. This review focus on the current understanding of regulatory mechanisms governing human gonadal sex differentiation by combining knowledge of these processes from studies in mice, information from patients with differences of sex development and insight from manipulation of selected signalling pathways in ex vivo culture models of human fetal gonads. |
| first_indexed | 2024-04-12T11:09:26Z |
| format | Article |
| id | doaj.art-b197ff4bce1041339c4627c785ec762a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T11:09:26Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b197ff4bce1041339c4627c785ec762a2022-12-22T03:35:40ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-06-011010.3389/fcell.2022.902082902082Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental ModelsMalene Lundgaard Riis0Malene Lundgaard Riis1Anne Jørgensen2Anne Jørgensen3Department of Growth and Reproduction, Copenhagen University Hospital—Rigshospitalet, Copenhagen, DenmarkInternational Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital—Rigshospitalet, Copenhagen, DenmarkDepartment of Growth and Reproduction, Copenhagen University Hospital—Rigshospitalet, Copenhagen, DenmarkInternational Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital—Rigshospitalet, Copenhagen, DenmarkSex-specific gonadal differentiation is initiated by the expression of SRY in male foetuses. This promotes a signalling pathway directing testicular development, while in female foetuses the absence of SRY and expression of pro-ovarian factors promote ovarian development. Importantly, in addition to the initiation of a sex-specific signalling cascade the opposite pathway is simultaneously inhibited. The somatic cell populations within the gonads dictates this differentiation as well as the development of secondary sex characteristics via secretion of endocrine factors and steroid hormones. Opposing pathways SOX9/FGF9 (testis) and WNT4/RSPO1 (ovary) controls the development and differentiation of the bipotential mouse gonad and even though sex-specific gonadal differentiation is largely considered to be conserved between mice and humans, recent studies have identified several differences. Hence, the signalling pathways promoting early mouse gonad differentiation cannot be directly transferred to human development thus highlighting the importance of also examining this signalling in human fetal gonads. This review focus on the current understanding of regulatory mechanisms governing human gonadal sex differentiation by combining knowledge of these processes from studies in mice, information from patients with differences of sex development and insight from manipulation of selected signalling pathways in ex vivo culture models of human fetal gonads.https://www.frontiersin.org/articles/10.3389/fcell.2022.902082/fullhuman fetal gonadssex-specific gonadal differentiationdifferences/disorders of sex developmentex vivo culture modelsfetal testis developmentfetal ovary development |
| spellingShingle | Malene Lundgaard Riis Malene Lundgaard Riis Anne Jørgensen Anne Jørgensen Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models Frontiers in Cell and Developmental Biology human fetal gonads sex-specific gonadal differentiation differences/disorders of sex development ex vivo culture models fetal testis development fetal ovary development |
| title | Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models |
| title_full | Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models |
| title_fullStr | Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models |
| title_full_unstemmed | Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models |
| title_short | Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models |
| title_sort | deciphering sex specific differentiation of human fetal gonads insight from experimental models |
| topic | human fetal gonads sex-specific gonadal differentiation differences/disorders of sex development ex vivo culture models fetal testis development fetal ovary development |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.902082/full |
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