Mutations that occur in the cell lineages of sperm or eggs can be transmitted to offspring. In humans, positive selection of driver mutations during spermatogenesis can increase the birth prevalence of certain developmental disorders1–3. Until recently, characterizing the extent of this selection in sperm has been limited by the error rates of sequencing technologies. Here we used the duplex sequencing method NanoSeq4 to sequence 81 bulk sperm samples from individuals aged 24–75 years. Our findings revealed a linear accumulation of 1.67 (95% confidence interval of 1.41–1.92) mutations per year per haploid genome driven by two mutational signatures associated with human ageing. Deep targeted and exome NanoSeq5 of sperm samples identified more than 35,000 germline coding mutations. We detected 40 genes (31 newly identified) under significant positive selection in the male germline that have activating or loss-of-function mechanisms and are involved in diverse cellular pathways. Most of t

Author summary Meiotic drivers, a class of selfish gene, are frequently located on sex chromosomes and have dramatic impacts on gamete development. However, our understanding of their molecular conseq...

Non-obstructive azoospermia (NOA) belongs to male infertility due to spermatogenesis failure. Howeve

Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of

Kedua proses ini sama-sama memengaruhi proses pembuahan, Ma

Abstract. Protamine 2 (Prm2/PRM2), together with Protamine 1 (Prm1/PRM1), constitute the two protamines found in both murine and human sperm. During spermi

Testis-specific transcript 10 (Tex10) is highly expressed in the testis, embryonic stem cells (ESCs), and primordial germ cells (PGCs). We previously generated a Tex10 knockout mouse model demonstrating its critical roles in ESC pluripotency and preimplantation development. Here, using conditional knockout mice and dTAG-degron ESCs, we show Tex10 is required for spermatogenesis and ESC-to-PGCLC differentiation. Specifically, Tex10-null spermatocytes arrest at metaphase I, compromising round spermatid formation. Tex10 depletion and overexpression compromise and enhance ESC-to-PGCLC differentiation, respectively. Mechanistically, bulk and single-cell RNA sequencing reveals that Tex10 depletion downregulates genes involved in pluripotency, PGC development, and spermatogenesis while upregulating genes promoting somatic programs. Chromatin occupancy study reveals that Tex10 binds to H3K4me3-marked promoters of Psmd3 and Psmd7, negative regulators of Wnt signaling, and activates their expres

Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potent

Chaperone-Mediated Autophagy (CMA) is a major pathway of lysosomal proteolysis involved in numerous

Seasonal spermatogenesis in fish is driven by spermatogonial stem cells (SSCs), which undergo a comp