Publication Date
9-1-2022
Journal
The FASEB Journal
DOI
10.1096/fj.202101168RR
PMID
35920200
PMCID
PMC9544956
PubMedCentral® Posted Date
8-3-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Chromatin, Female, Fertility, Male, Meiosis, Mice, Spermatocytes, Spermatogenesis, Y Chromosome, diplotene, liquid–liquid phase separation, male infertility, pachytene, subnuclear, XY body
Abstract
Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet‐like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body chromatin during diplotene. We demonstrate that Mrnip −/− spermatocytes have impaired DNA double‐strand break (DSB) repair, they display reduced sex body formation and defective MSCI. We show that Mrnip −/− undergoes critical meiocyte loss at the diplotene stage. Furthermore, we determine that DNA DSBs (induced by SPO11) and synapsis initiation (facilitated by SYCP1) precede Mrnip expression in testes. Altogether, our findings indicate that in addition to an emerging role in DNA DSB repair, MRNIP has an essential function in spermatogenesis during meiosis I by forming drop‐like accumulations interacting with the sex body.
Included in
Immunology of Infectious Disease Commons, Immunopathology Commons, Medical Immunology Commons, Pathology Commons