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Meiotic prophase I disruption as a strategy for non-hormonal male contraception using small-molecule inhibitor JQ1 [RNA-seq]

ABSTRACT: The small-molecule bromodomain inhibitor JQ1 transiently suppresses spermatogenesis by targeting BRDT, a testis-specific transcriptional regulator required for meiotic and post-meiotic differentiation. To define the transcriptional and cellular consequences of JQ1 exposure and recovery, we performed single-cell RNA sequencing (scRNA-seq) of mouse testes collected from untreated controls, JQ1-treated males, and recovery cohorts following treatment withdrawal. This dataset includes 15 libraries representing all experimental groups and captures germ cell and somatic populations spanning spermatogonial, meiotic, and spermiogenic stages. The data provide a comprehensive transcriptional atlas of JQ1-induced meiotic disruption and subsequent restoration of spermatogenesis, supporting mechanistic and contraceptive studies of BRDT inhibition.

ORGANISM(S): Mus musculus

PROVIDER: GSE310340 | GEO | 2026/03/23

REPOSITORIES: GEO

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Meiotic prophase I disruption as a strategy for non-hormonal male contraception using small-molecule inhibitor JQ1

Project description:The small-molecule bromodomain inhibitor JQ1 transiently suppresses spermatogenesis by targeting BRDT, a testis-specific transcriptional regulator required for meiotic and post-meiotic differentiation. To define the transcriptional and cellular consequences of JQ1 exposure and recovery, we performed single-cell RNA sequencing (scRNA-seq) of mouse testes collected from untreated controls, JQ1-treated males, and recovery cohorts following treatment withdrawal. This dataset includes 15 libraries representing all experimental groups and captures germ cell and somatic populations spanning spermatogonial, meiotic, and spermiogenic stages. The data provide a comprehensive transcriptional atlas of JQ1-induced meiotic disruption and subsequent restoration of spermatogenesis, supporting mechanistic and contraceptive studies of BRDT inhibition.

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Project description:JQ1 is a small-molecule (BET family) bromodomain inhibitor that causes a contraceptive effect in mice by blocking spermatogenesis and reducing sperm motility.

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Project description:Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential meiotic genes and repressing a “progenitor cells” gene expression program, while “priming” a post-meiotic gene group for further activation. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdt’s first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome. Total RNA obtained from testes from prepuberal mice at 17dpp and at 20dpp were compared between Brdt-/- and Brdt+/- (17dpp), between Brdt-/- and Brdt +/+ (20dpp) and between BrdtBD1del and Brdt wt mice (20dpp). In each experiments, 6 replicates of each genotype and condition were used.

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