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Structural and functional characterization of long non-coding RNA implicated in the production and motility of sperm

@INRAE B. Mandon-Pépin (Localisation of lncRNA 4930463O16Rik by in situ Hybridization (red) on testicule sections from 2-month old mice. Immunofluorescence labelling with anti-DDX4 antibodies (green) to visualize the cytoplasm of germ cells and DAPI coloration (blue) to visualize nuclear chomosomes. White squares: spermatocytes before the first meiosis division. White circles: sperm obtained after 2 meiosis divisions.)
Inactivation of the gene Topaz1 causes sterility in male mice due to the blockage of spermatogenesis leading to a dysregulation of numerous long non-coding RNA (LncRNA) in the testicules. One of the lncRNA was tudied and its inactivation presents a different phenotype than that of Topaz1. The concentration of sperm was decreased by half in these animals and their motility was altered.

Topaz1 is a gene initially discovered in the fetal ovaries of ewes during meiosis. It is well conserved in vertebrates and its expression is specific of germ cells. A murine model lacking the gene Topaz1 (KO), was generated. This allowed to identify its role in male fertility. The absence of this gene leads to meiotic arrest after prophase I and a chromosome misalignment at the metaphase I plate.

In order to better characterize the tecticule phenotype of Topaz 1-/- mice, high-throughput transcriptomic analyses were done by RNA sequencing. The absence of TOPAZ1 disturbs the expression of genes implicated in the mobility of microtubules and/or the cilium, biological processes necessary for spermatogenesis. In addition, one quarter of the dysregulated genes are lncRNA specific for male germ cells of which some are not expressed in Topaz1 -/- testicules. A mouse line in which the expression of one of these lncRNA (4939463O16Rik) was suppressed showed that fertility in these mice is not affected. Yet certain sperm parameters are modified and the concentration of sperm decreased by half in these animals.

This work identifies a lncRNA (4930463O16Rik) whose expression is dependent on Topaz1 and that is the key element, for both the production and motility of sperm.

See also

Reference:

Chadourne Manon, Poumerol Elodie, Jouneau Luc, Passet Bruno, Castille Johan, Sellem Eli, Pailhoux Eric, Mandon-Pépin Béatrice.Structural and Functional Characterization of a Testicular Long Non-coding RNA (4930463O16Rik) Identified in the Meiotic Arrest of the Mouse Topaz1–/– Testes. Frontiers in Cell and Developmental Biology. 2021. 9: 1771. DOI=10.3389/fcell.2021.700290    
Contact : Béatrice Mandon-Pépin (beatrice.mandon-pepin(at)inrae.fr)
For more information: https://www.frontiersin.org/article/10.3389/fcell.2021.700290