TRAPPC2l Participates in Male Germ Cell Development by Regulating Cell Division

TL;DR

TRAPPC2L is essential for male germ cell development by preventing premature meiosis and maintaining cell division control.

Contribution

This study reveals a novel role of TRAPPC2L in regulating male germ cell development through cell division control.

Findings

Knockout of Trappc2l in male mice leads to infertility due to abnormal germ cell development.

Germ cell syncytial structures form in Trappc2l-deficient mice, likely due to abnormal cell division.

Meiosis-associated genes are expressed prematurely in Trappc2l-deficient germ cells.

Abstract

TRAPPC2L is a core subunit of the Transport Protein Particle (TRAPP) complex, which is involved in vesicle transport and autophagy. Mutations in Trappc2l gene are associated with neurodevelopmental disorders, characterised by severe neurodevelopmental delays and varying degrees of muscle abnormalities. In this study, we found that the knockout of Trappc2l did not cause developmental abnormalities in both male and female mice. However, the male mice were completely infertile. Histological examination revealed that germ cell syncytial structures with multiple nuclear were formed in Trappc2l knockout mice from embryonic day 17.5 (E17.5) and the number and size of these structures gradually were increased at later developmental stages. The germ cells were completely lost at 2 weeks after birth. Further study found that germ cell syncytial structures were most likely formed by abnormal cell division but not cell fusion. We also found that meiosis‐associated genes Stra8 and Sycp3 were expressed in Trappc2l‐deficient germ cells during the embryonic stage. Our study demonstrated that Trappc2l is essential for germ cell development in male mice which is probably involved in keeping the mitotic quiescent state of male germ cells during the embryonic stage.

Trappc2l is crucial for maintaining the quiescent state of male gonocytes. In the absence of Trappc2l, the quiescent state of gonocytes is disrupted, leading to premature and abnormal initiation of meiosis, which consequently results in subsequent abnormalities in sperm development.

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