This report describes a fly model of azoospermia, Sertoli cell-only syndrome. In humans, there are both Y-linked and X-linked forms of this syndrome. Hypomorphic mutations in the Drosophila gene bel, which encodes a DEAD-box RNA helicase, have been found to result in the specific loss of germline cells in the testis, whereas somatic cells are maintained; this phenotype recapitulates that observed for Sertoli cell-only syndrome. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for the Dmel\bel gene.
One of the two human orthologs of Dmel\bel, DEAD-box helicase 3, Y-linked (DDX3Y), is within the region of the Y chromosome implicated in Sertoli cell-only syndrome. The second orthologous human gene, DDX3X, is located on the X chromosome. Neither human gene has been introduced into flies.
Homozygous amorphic alleles of Dmel\bel are lethal; hypomorphic mutations result sterility or semi-sterility in both sexes. Unlike the human DDX3 genes, the Dmel\bel gene is located on an autosomal chromosome; there are no closely related paralogs in Drosophila. Genetic and physical interactions of Dmel\bel have been described; see below and in the bel gene report.
[updated Jun. 2017 by FlyBase; FBrf0222196]
Non-obstructive azoospermia (NOA) is defined as absence of any measurable level of sperm in semen, resulting from a defect in the production of spermatozoa in the testes. [from MedGen, Non-obstructive azoospermia; MedGen UID: 866757]
Non-obstructive azoospermia (NOA), or failure of spermatogenesis within the testis, is diagnosed in approximately 10% of infertile men. NOA may be due to a lack of appropriate stimulation by gonadotropins, in which case hormonal therapy is usually effective. A larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment. In these cases, the primary approach is to improve the quantity and quality of sperm retrieved from the testis for use for in vitro fertilization (Kumar, 2013; PMCID:PMC3583162).
[SPERMATOGENIC FAILURE, Y-LINKED, 1; SPGFY1](https://omim.org/entry/400042)
[SPERMATOGENIC FAILURE, Y-LINKED, 1; SPGFY1](https://omim.org/entry/400042)
Sertoli cells are somatic cells of the testis; they are found in the seminiferous tubules, where meiosis occurs and the spermatozoa are produced.
In the evaluation of male infertility, the Sertoli cell-only (SCO) syndrome is diagnosed on testicular biopsy when either no germ cells are visible in any seminiferous tubules (SCO type I) or germ cells are present in a minority of tubules (SCO type II) (Sargent et al., 1999; pubmed:10507722). [from MIM:305700, MIM:400042; 2017.06.01]
There are Y-linked (MIM:400042)and X-linked (MIM:305700) forms of Sertoli cell-only syndrome. The Y-linked form has been associated with deletions of the 'azoospermia factor' (AZF) region; this region includes several genes, one of which is DDX3Y (DEAD-box helicase 3, Y-linked). [from MIM:400042; 2017.06.01] There is also a DEAD-box helicase 3 gene on the X-chromosome (DDX3X). [from MIM:300160; 2017.06.01]
Many to one: 2 human to 1 Drosophila; the 2 human genes are DDX3Y and DDX3X.
Many to one: 2 human to 1 Drosophila; the 2 human genes are DDX3Y and DDX3X.
High-scoring ortholog of human DDX3Y and DDX3X (1 Drosophila to 2 human); Dmel\bel shares 51% identity and 61% similarity with the human genes.
