ArticleJournal of assisted reproduction and genetics2026
TEX43, a testis-enriched microtubule-associated gene, exerts minimal impact on spermatogenesis and fertility in mice and humans.
Article in Journal of assisted reproduction and genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTestis-specific TEX family genes are critical for spermatogenesis, but TEX43's function and subcellular localization remain uncharacterized. This study aimed to delineate TEX43's localization, molecular function and role in spermatogenesis and fertility using murine models and clinical data.
methodsTex43 expression was analyzed via quantitative reverse transcription-polymerase chain reaction (Q-PCR), immunohistochemistry (IHC), and western blotting. A Tex43 knockout (KO) mouse model was generated using CRISPR/Cas9 (targeting exons 1-3). Testicular histology (hematoxylin-eosin [H&E] staining), sperm parameters (morphology via H&E smears, density via hemocytometer, motility via computer-assisted sperm analysis [CASA]), and fertility (in vivo breeding assays, in vitro fertilization [IVF]) were evaluated. Sperm ultrastructure was assessed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Whole-exome sequencing (WES) identified TEX43 variants in 146 infertile men with asthenoteratozoospermia. Variant characterization was performed via Sanger sequencing and pedigree analysis. Structural modeling of WT/mutant TEX43 was performed via SWISS-MODEL.
resultsTex43 is testis-enriched: mRNA expression initiated at postnatal day 18 (round spermatid stage) and peaked in elongating spermatids; TEX43 localized to sperm flagellar microtubules. Tex43-KO mice showed modestly reduced sperm density (28.6 ± 3.2 vs. 41.2 ± 2.9 × 10⁶ sperm/ml in WT; P < 0.01) but normal testicular architecture, sperm motility, and fertility (litter size: KO 6.8 ± 0.7 vs. WT 7.2 ± 0.5 pups/litter; P > 0.05). TEM revealed increased flagellar end piece "9 + 2" microtubule disorganization in KO sperm (~ 30% vs. ~ 5% in WT; P < 0.01). WES identified 5 infertile men with TEX43 variants; The missense variant p.R37Q (c.110G > A) was predicted to weaken TEX43-microtubule binding. SEM/TEM of patient sperm harboring p.R37Q confirmed microtubule disorganization. Four patients with exonic variants achieved live births via ICSI.
conclusionsTEX43, localized to the sperm flagellar microtubules, plays a subtle role in murine spermatogenesis by stabilizing axonemal structure, with genetic redundancy mitigating overt fertility defects. Human TEX43 variants may exert subtle reproductive effects, but are amenable to ICSI, requiring validation in larger cohorts with functional studies. These finding advance understanding of testis-specific microtubule-associated proteins in sperm biology and inform clinical interpretation of TEX43 variants in infertility.
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