1. Adamts9 is required for the development of primary ovarian follicles and maintenance of female sex in zebrafish†
- Author
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Carver, Jonathan J, Amato, Ciro M, Hung-Chang Yao, Humphrey, and Zhu, Yong
- Abstract
Previous studies have suggested that adamts9(a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and is necessary for female fertility. In this study, we found that adamts9knockout (KO) led to reduced body size, and female-to-male sex conversion in late juvenile or adult zebrafish; however, primary sex determination was not affected in early juveniles of adamts9KO. Overfeeding and lowering the rearing density rescued growth defects in female adamts9KO fish but did not rescue defects in ovarian development in adamts9KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicles) in early juveniles of adamts9KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9KO. Taken together, our results indicate that adamts9is critical for development of primary ovarian follicles and maintenance of female sex, and loss of adamts9leads to defects in ovarian follicle development, female infertility, and sex conversion in late juveniles and mature adults. These results show that the ECM and extracellular metalloproteases play major roles in maintaining ovarian follicle development in zebrafish.Arrested primary ovarian follicles and female to male sex conversion in Adamts9 KO zebrafish are due to dysregulation of extracellular matrix.Graphical Abstract
- Published
- 2024
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