BioProject

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 necessary for female fertility. More...

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 necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female to male sex conversion in adult mature zebrafish prior to or after 90 days post fertilization (dpf); however, primary sex determination was not affected in early juveniles of adamts9 KO at 35 dpf. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicle) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO 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 adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex in zebrafish, and loss of adamts9 in zebrafish leads to ovarian follicle arrest, female infertility, and sex conversion in late juveniles and mature adults. Overall design: To investigate the role of adamts9 in zebrafish ovary formation and maintainence, we conducted mRNA sequencing on wildtype and mutant ovaries at dpf 41 and 67. Less...