Biology subjects

Kotaja, N.

Publications and source records attributed to Kotaja, N..

5 recordsLinked to original sources

bioRxiv2026

Male youth BMI is associated with epigenetic ageing of female descendants but not blood or sperm DNA methylation

Studies based on harvest records indicate that grandparental nutrition in youth is associated with the health traits of grandchildren in a sex-specific lineage. We investigated whether male early adulthood anthropometrics associate with epigenetic age, a measure of general well-being, and DNA methylation, a potential molecular inheritance mechanism, in three generations of descendants. Data on weight, height, BMI and chest circumference measured at military draft examinations (at age 18-24 yrs.) were retrieved from national archives for 1,013 men, herein referred to as Generation Archives (GA). The genome-wide DNA methylation of their descendants participating in the Young Finns Study (YFS) was measured from the blood and sperm from the children (59-80 yrs., nblood = 362, nsperm = 51), grandchildren (34-49 yrs., nblood = 421, nsperm = 98) and great-grandchildren (7-30 yrs., nblood = 200). The men's (GA) BMI had an inverse association with the epigenetic pace of ageing (DunedinPACE) of their daughters ({beta} = -0.01, p = 0.002, n = 169) and the daughters' daughters ({beta} = -0.01, p = 0.049, n = 126) but not with that of their male descendants. From within the YFS cohort, maternal, but not paternal, BMI at ages 13-34 also had an inverse association with the DunedinPACE of the immediate offspring. However, robust evidence for the inheritance mechanism was not found in the analyses between the anthropometric measurements of the GA men and the DNA methylation profiles in the blood and sperm of their descendants.

molecular biology↗

bioRxiv2026

Transcriptome profiling identifies the chromatoid body as a dynamic center for RNA surveillance and transcript sorting during spermatogenesis

The chromatoid body (CB) is a hallmark of haploid male germ cells, but how it selects and regulates RNAs has remained unclear. Here we define the RNA landscape of the CB by transcriptome and small RNA profiling of isolated CBs throughout mouse round spermatid differentiation. We find that the CB selectively concentrates pachytene piRNAs, retrotransposon transcripts, specific mRNA isoforms and intron-retaining mRNAs, revealing extensive RNA sorting within this cytoplasmic germline condensate. The enrichment of transposable element transcripts together with PIWI-piRNA complexes identifies the CB as a surveillance center that may safeguard genome integrity in post-meiotic haploid cells. Unexpectedly, mRNA recruitment is not determined by predicted piRNA targeting. Instead, transcript localization is encoded by a combinatorial set of intrinsic sequence and structural features that accurately predict CB enrichment at isoform resolution. These findings establish the CB as a dynamic post-transcriptional regulatory compartment that integrates genome surveillance, RNA quality control and selective transcript sorting, uncovering general principles through which biomolecular condensates shape cell-specific transcriptomes.

bioinformatics↗

bioRxiv2026

Chromatoid body integrates piRNA, SMG6 and m⁶A pathways to control mRNAs in the male germline

Spermatogenesis requires tightly controlled transcriptome regulation, supported by the PIWI-interacting RNA (piRNA) and nonsense-mediated decay (NMD) pathways, both concentrated in the chromatoid body (CB) of haploid spermatids. We previously showed that the NMD endonuclease SMG6 interacts with the piRNA-binding protein PIWIL1, and that loss of either factor results in overlapping mRNA dysregulation, suggesting functional cooperation. Here, we demonstrate that SMG6 and PIWIL1 assemble with shared RNA-regulatory proteins and bind common mRNA targets in the testis. Functional experiments in GC-2spd cells revealed cooperative regulation of selected transcripts, including Ccny and Taf1d, and established that SMG6 is required for piRNA-guided degradation of these targets, implicating its endonuclease activity in the piRNA pathway. Target mRNAs were mA-methylated, and this modification shaped their expression levels, SMG6 binding, and CB localization. Moreover, intact target mRNAs accumulated in CBs isolated from Smg6-cKO testes, indicating defective CB-associated decay. Together, these findings uncover a key role for the CB in mRNA regulation through coordinated action of the NMD and piRNA pathways.

cell biology↗

bioRxiv2025

Tissue-resident neutrophils serve homeostatic and immunological functions in embryos

Development of neutrophils in the bone marrow and their crucial role in first-line defense are well understood in adults, but remarkably little is known about fetal neutrophils. Here, we analyzed the production, distribution, and functions of neutrophils during embryonic development in the mouse. We discovered that multiple non-hematopoietic steady-state organs harbor substantial numbers of immature and mature neutrophils, many of which are localized to tissue parenchyma outside the vessels. Using single-cell transcriptomic analyses, we revealed the presence of neutrophil progenitors and precursor cells in the blood and even in non-hematopoietic tissues in fetal and newborn mice. Embryonic tissue-resident neutrophils were transcriptionally different from embryonic blood-borne neutrophils and adult neutrophils. We demonstrated, through functional analyses, that embryonic neutrophils proliferated actively, had a high glycolytic capacity, and exhibited distinct diurnal rhythmicity. Embryonic neutrophils displayed lineage-specific innate immune effector functions and were responsive to maternal immunostimulation and immunosuppression. Using a genetic embryonic neutrophil depletion model, we discovered that neutrophils impact the piRNA pathway in the testis. Collectively, our data provides an atlas of the fetal neutrophil landscape and dissects their responses in steady-state. SummaryNon-hematopoietic steady-state tissues harbor extravascular immature and mature neutrophils during fetal development. Embryonic neutrophils are endowed with multiple effector mechanisms and also serve homeostatic roles during tissue development.

immunology↗

bioRxiv2023

Exposure to childhood maltreatment is associated with changes in sperm small non-coding RNA and DNA methylation profiles

BackgroundChildhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the paternal germ line. The contribution of paternal early life stress on the health of the next generation in humans is not fully elucidated. MethodsIn this study, we measured paternal CME using the Trauma and Distress Scale (TADS) questionnaire and mapped sperm-borne sncRNAs expression by small RNA sequencing (small RNA-seq) and DNA methylation (DNAme) in spermatozoa by reduced-representation bisulfite sequencing (RRBS-seq) in males from the FinnBrain Birth Cohort Study. The study design was a (nested) case-control study, high-TADS (TADS [≥] 39, n = 25 for DNAme and n = 14 for small RNA-seq) and low-TADS (TADS [≤] 10, n = 30 for DNAme and n = 16 for small RNA-seq)). Groups were compared to identify specific epigenetic signatures associated with TADS levels in the spermatozoa of participants. ResultsCompared to the control group, high CME was associated with altered sperm sncRNA expression and DNAme profiles. Particularly, we identified several tRNA-derived small RNAs (tsRNAs) and miRNAs with markedly changed levels in males with high CME. DNA methylation analysis identified several genomic regions with differentially methylated CpGs between groups. Notably, we identified two epigenetic marks related to brain development with distinct profiles between CME and controls, the miRNA hsa-mir-34c-5p and differential methylation of the region in proximity of FSCN1. ConclusionsThis study provides further evidence that early life stress influences the paternal germ line epigenome and supports a possible contribution in the development of the central nervous system of the next generation.

molecular biology↗