Male infertility is a universal, but under-diagnosed issue involving 15% of couples around the world. Possible semen phenotypes are azoospermia, oligozoospermia, asthenozoospermia and teratozoospermia. Atrophic non-obstructive azoospermia: the inability to sterilise or spermatinate (either Sertoli cell-only phenotype (SCO), spermatogonial arrest (SpgA), meiotic arrest (MeiA), round spermatid arrest (RsA) or hypospermatogenesis (Hyposp).
While infertility may be a multifactorial phenomenon, genetics is central to reproductive outcomes. Spermatogenesis is a multigene phenomenon. Genes for male germ cells must be found and described to learn the hows and whys of cell development. Testis expressed (TEX) relatives were detected in other vertebrates (mammals, birds and reptiles), invertebrates and yeast. There are currently 69 TEX genes in existence in species and tissues. For male infertility, the most prevalent genes at present are pathogenic versions of TEX11, TEX14 and TEX15. Infertility in men, as we know it, is a genetic condition for which precise diagnostic and therapeutic interventions are needed.
Fig. 1 The transcription of TEX genes in different species (Bellil, H.; et al.2021).
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TEX Genes in Male Infertility
It is under-expressed in pachytene spermatocytes and over-expressed in postmeiotic germ cells. Females lacking TEX15 are fertile; males are infertile, with their testis slashed by 80 per cent and the total absence of pachytene spermatocytes and post-meiotic germ cells.
| TEX Genes |
Description |
| TEX18 |
Male TEX18 mice become subfertile as sperm morphology and motility are hampered, a condition called asthenoteratozoospermia. Spermatids mature unidirectionally and have some partial degeneration in seminiferous tubules, so TEX18 probably only comes out during spermatid differentiation. |
| TEX19 |
The protein TEX19.1 encodes exists only in germ cells and pluripotent cells. TEX19.1-mutant male mice are unfertile, lacking meiotic chromosome synapsis, DNA DSBs at meiosis, and post-meiotic loss of germ cells. |
| TEX27 |
TEX27 appears only in adult mouse testes. It codes for a protein whose carboxyl-terminal domain is a zinc finger domain and its amino-terminal domain is a transactivation domain. TEX27 could be a transcription factor which is repressed more heavily in postmeiotic cells during spermatogenesis in mice. |
| TEX33 |
TEX33 is expressed only in the testis; the encoded protein is present in the cytoplasm of round spermatids but not so much in elongated ones. Given that spermatogenesis is normal in male TEX33 knockout mice, perhaps TEX33 isn't needed. |
| TEX36 |
It's only present in testicle but male mice knocked out for TEX36 remain fertile with no visible defects in the genitals, and so neither is TEX36 required for spermatogenesis. |
| TEX37 |
Similar to TEX36, TEX37 knockout male mice are also fertile and have no detectable defects in testis/body weight ratio, epididymal sperm count, and testicular and epididymal histology (compared with wild-type mice). |
| TEX40 |
The TEX40 protein (CATSPERZ) is localised at the front of the flagellum. Fertility and sperm count and morphology in TEX40 knockout mice are normal. But the flagella are stiff, which slows the sperm's movements and reduces fertility both in humans and in vitro. |
| TEX101 |
TEX101 is predominantly found in the testis (from spermatogonia to spermatids), but it is also transscribed during oogenesis. Mouse TEX101 is a germ cell-specific protein of the testis that's found primarily on the germ cell plasma membrane during development. |
| TEX261 |
TEX261 might be involved in many neurological disorders. TEX261 knockout mice lack bone, immune system, growth/size/body and fat tissue. |
| TEX264 |
TEX292 also known as Utp4. Deletion of TEX292 kills embryos. |
Human TEX Gene Expression and Defects
mRNA Expression
Of the 49 TEX genes expressed in humans, 13 are testis-specific and 27 show high expression levels in the testis with mean testis ratios exceeding 0.4 (ranging between 0.411 and 0.998).
Protein Expression
For 14 TEX genes, protein expression patterns were similar to mRNA expression patterns. Testis-specific protein isoforms have been identified for 29 TEX genes, while expression data for the other 14 genes are missing.
Conclusion
TEX genes have a close affinity to reproductive function and defects can be linked to male infertility. TEX genes are found mostly in germ cells, and they are required for sperm maturation. Because all TEX genes have the same function - they're only expressed in the testis – they're involved in a wide range of pathways and functions in testicles, germ cells (spermatogonia to spermatids), Sertoli cells and Leydig cells. Out of the diverse TEX gene family, genes with known pathogenicity are TEX11, TEX14 and TEX15. TEX13A, TEX13B, TEX13C, FAM9A (TEX39A) and FAM9B (TEX39B), then, are all only candidate genes for azoospermia.
Sooner or later, cumulative information about physiological roles and pathophysiological dysfunctions of human TEX genes will be accessible. Then there are the functional implications of natural knockout or knockdown in humans, whose list of essential and non-essential testis-specific genes and proteins is required to continue human reproductive biology.
References
- Wenzek F.; et al. Nicotinamide riboside: What it takes to incorporate it into RNA. Molecules. 2024, 29(16): 3788.
- Bellil, H.; et al. Human testis-expressed (TEX) genes: a review focused on spermatogenesis and male fertility. Basic and clinical andrology. 2021, 31(1): 9.
- Sieper, M.; et al. Scrutinizing the human TEX genes in the context of human male infertility. Andrology. 2024, 12(3): 570-584.
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