Alterations of sex determination pathways in the genital ridges of males with limited Y chromosome genes†
| Autor: | Monika A. Ward, Mayumi Fernandez, Eglė A. Ortega, Quinci Salvador |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Gonad Genotype Offspring Embryonic Development Mice Transgenic Biology Y chromosome Andrology Mice 03 medical and health sciences 0302 clinical medicine Y Chromosome medicine Homologous chromosome Animals X chromosome 030219 obstetrics & reproductive medicine Sexual differentiation Days post coitum Gene Expression Regulation Developmental Cell Biology General Medicine Sex Determination Processes 030104 developmental biology Testis determining factor medicine.anatomical_structure Reproductive Medicine RNA Research Article |
| Zdroj: | Biology of Reproduction. 100:810-823 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1093/biolre/ioy218 |
| Popis: | We previously demonstrated that in the mouse only two Y chromosome genes are required for a male to produce an offspring with the help of assisted reproduction technologies (ART): testis determinant Sry and spermatogonial proliferation factor Eif2s3y. Subsequently, we have shown that the function of these genes can be replaced by transgenic overexpression of their homologs, autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y chromosome contribution limited to two (X(Eif2s3y)OSry), one (X(Eif2s3y)OSox9 and XOSry,Eif2s3x), and no genes (XOSox9,Eif2s3x) produced haploid germ cells and sired offspring after ART. However, despite successful assisted reproductive outcome, they had smaller testes and displayed abnormal development of the seminiferous epithelium and testicular interstitium. Here we explored whether these testicular defects originated from altered pro-testis and pro-ovary factor signaling in genital ridges at the time of sex determination. Timed pregnancies were generated to obtain transgenic X(Eif2s3y)OSry, X(Eif2s3y)OSox9, XOSry,Eif2s3x, XOSox9,Eif2s3x, and wild-type XX and XY fetuses at 12.5 days post coitum. Dissected genital ridges were assessed for their morphology and anatomy, and expression of pro-testis and pro-ovary transcripts. All transgenic males displayed incomplete masculinization of gonadal shape, impaired development of testicular cords and gonadal vasculature, and decreased expression of factors promoting male pathway. Fetal gonad masculinization was more effective when sex determination was driven by the Sry transgene, in the presence of Y chromosome genes, and to a lesser extent a double dosage of X genes. The study adds to the understanding of the role of Y chromosome genes and their homologs during sex determination. |
| Databáze: | OpenAIRE |
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