A Novel Compound Heterozygous Mutation in TEX14 Causes Human Non-Obstructive Azoospermia by Disrupting the Assembly of Intercellular Bridges.

Abstract

Intercellular bridges (ICBs) are critical in intercellular communication, coordinated cellular development, and the equilibration of cytoplasmic contents between germ cells during vertebrate spermatogenesis. Mammalian TEX14 is specifically expressed in the testes and is a pivotal component of ICBs. It is indispensable for proper spermatogenesis; its deficiency causes meiotic arrest at the pachytene stage of meiotic prophase I, resulting in male infertility with non-obstructive azoospermia (NOA) in murine models. However, the specific effects of TEX14 deficiency on spermatogenesis remain poorly understood. In this study, we identified a novel compound heterozygous mutation in TEX14 (c.802A>T, p.S268C and c.1021C>T, p.R341*) in a patient with NOA. Functional analyses demonstrated that these mutations disrupted TEX14 synthesis. This led to spermatogenic failure characterized by meiotic arrest at the pachytene stage and impaired ICB assembly in the testes harboring the mutations. Our findings provide robust evidence that pathogenic biallelic TEX14 mutations are recurrent genetic etiologies of NOA in humans.