Biology subjects

Jansson, T.

Publications and source records attributed to Jansson, T..

5 recordsLinked to original sources

bioRxiv2025

A Novel Framework for Quantitative Analysis of Neuronal Primary Cilia in Brain Tissue

BackgroundAccurate analysis of neuronal primary cilia is essential for understanding developmental processing of neurons. But existing image segmentation methods struggle with staining variability and background noise. To address this, we developed a more robust segmentation and statistical analysis pipeline using an animal model small sample size and with known neuronal microstructure alterations. MethodsMaternal obesity was induced in mice via a high-fat/high-sucrose diet. Hippocampal tissue from 6-month-old offspring of obese and control dams was analyzed. We developed a MATLAB-based pipeline to segment neuronal cilia from z-stack images, applying mathematical transformations and using the Weibull distribution and Bayesian Information Criterion (BIC) to assess group differences ResultsThe technique segmented cilia despite artifacts, revealing group-specific patterns. Statistical analysis confirmed significant differences, highlighting the methods robustness over traditional tests, especially with small samples. ConclusionOur method reliably segments neuronal primary cilia in immune-stained sections with thionin-counter staining and offers a sensitive, assumption-free alternative to traditional statistical tests, ideal for small-sample neurobiological studies

neuroscience↗

bioRxiv2025

HUMAN FETAL CIRCULATING FACTORS FROM PREGNANCIES COMPLICATED BY MATERNAL OBESITY INDUCE HYPERTROPHY IN NEONATAL RAT CARDIOMYOCYTES

AimObesity in pregnant women increases offspring cardiovascular risk and causes fetal cardiac dysfunction. The underpinning mechanisms remain unclear. We hypothesised that circulating factors in serum from fetuses of women with obesity induce pathological cardiomyocyte hypertrophy. MethodsPregnant women with obesity or healthy weight were recruited at term and provided umbilical cord serum and placentas, which were used for isolation of primary trophoblast cells. Primary cardiomyocytes were isolated from neonatal rats. ResultsCompared to serum-free medium, supplementing cardiomyocytes with umbilical cord serum increased their mRNA expression of atrial natriuretic factor (Anf) and brain natriuretic peptide (Bnp), hallmarks of pathological hypertrophy, but did not alter their size. Cord serum from women with obesity further upregulated cardiomyocyte Anf and Bnp, and increased the ratio of beta- to alpha-myosin heavy chain expression (Myh7:Myh6), compared to cord serum from healthy weight women. This effect was prevented by treating the cord serum with heat- freeze cycling and DNase or RNase digestion. Conditioned medium from trophoblast cells from women with obesity also increased cardiomyocyte Anf, Bnp and Myh7:Myh6 expression. MicroRNAs miR-142 and miR-17, which are associated with cardiac function, were increased in abundance in extracellular vesicles isolated from cord serum from women with obesity. However, miR-142-3p, miR-142-5p and miR-17-5p did not increase Anf, Bnp or Myh7:Myh6 expression when they were transfected into cardiomyocytes. ConclusionThe results show that human fetal circulating and placenta-derived factors induce hallmarks of pathological hypertrophy in cardiomyocytes and may mediate cardiac dysfunction in children of women with obesity.

physiology↗

bioRxiv2024

PiggyBac Transposase Mediated Inducible Trophoblast-specific Knockdown of Mechanistic Target of Rapamycin in Mice Decreases Placental Nutrient Transport and Inhibits Fetal Growth.

Abnormal fetal growth is associated with perinatal complications and adult disease. The placental mechanistic target of rapamycin (mTOR) signaling activity is positively correlated to placental nutrient transport and fetal growth. However, if this association represents a mechanistic link, it remains unknown. We hypothesized that trophoblast-specific mTOR knockdown in late pregnant mice decreases placental nutrient transport and inhibits fetal growth. PiggyBac Transposase-Enhanced Pronuclear Injection was performed to generate transgenic mice containing a trophoblast-specific Cyp19I.1 promoter-driven, doxycycline-inducible luciferase reporter transgene with a Mtor shRNAmir sequence in its 3 untranslated region (UTR). We induced mTOR knockdown by administration of doxycycline starting at E14.5. Dams were euthanized at E 17.5, and trophoblast-specific gene targeting was confirmed. Placental mTOR protein expression was reduced by [~]68% in these animals, which was associated with a marked inhibition of mTORC1 and mTORC2 signaling activity. Moreover, we observed a decreased expression of System A amino acid transporter isoform SNAT2 and the System L amino acid transporter isoform LAT1 in isolated trophoblast plasma membranes and lower fetal but not placental weight. Inhibition of trophoblast mTOR signaling in late pregnancy is mechanistically linked to decreased placental nutrient transport and reduced fetal growth. Modulating placental mTOR signaling may represent a novel intervention in pregnancies with abnormal fetal growth.

physiology↗

bioRxiv2021

Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice

Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk but its effect on myocardial metabolism is unknown. We hypothesised that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day, E18.5; term{approx}E21) and offspring were studied at 3, 6, 9 or 24 months postnatally. Maternal obesity increased heart weight and peroxisome proliferator activated receptor {gamma} (Pparg) expression in female and male fetuses and caused left ventricular diastolic dysfunction in the adult offspring. Cardiac dysfunction progressively worsened with age in female, not male, offspring of obese dams, compared to age-matched controls. In 6-month-old offspring, exposure to maternal obesity increased cardiac palmitoyl carnitine-supported mitochondrial respiration in males and reduced myocardial 18F-fluorodeoxyglucose uptake in females. Cardiac Pparg expression remained higher in adult offspring of obese than control dams and correlated with contractile and metabolic function. Maternal obesity did not affect cardiac palmitoyl carnitine respiration in females or 18F-fluorodeoxyglucose uptake in males, or alter cardiac 3H-oleic acid uptake, pyruvate respiration, lipid content or fatty acid/glucose transporter abundance in offspring of either sex. The results support our hypothesis and show that maternal obesity affects offspring cardiac metabolism in a sex-dependent manner. Persistent upregulation of Pparg expression in response to overnutrition in utero may mechanistically underpin programmed cardiac impairments and contribute to cardiovascular disease risk in children of women with obesity.

physiology↗

bioRxiv2021

Insulin-stimulated adiponectin secretion in pregnancy is mediated by inhibition of adiponectin ubiquitination and degradation and is impaired in obesity

In pregnancy, adiponectin serves as an endocrine link between maternal adipose tissue, placental function and fetal growth, with low adiponectin promoting placental function and fetal growth. Circulating adiponectin levels are decreased in obese pregnant women and in gestational diabetes, which is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms governing adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood. Using visceral adipose tissue from lean and obese pregnant mice, we show that obesity in pregnancy is associated with adipose tissue inflammation, ER stress, insulin resistance, increased adiponectin ubiquitination and decreased total abundance of adiponectin. Moreover, adiponectin ubiquitination was increased in visceral fat of obese pregnant women as compared to lean pregnant women. We further observed that insulin prevents, whereas ER stress and inflammation promote, adiponectin ubiquitination and degradation in differentiated 3T3-L1 adipocytes. We have identified key molecular pathways regulating adiponectin secretion in pregnancy. This information will help us better understand the mechanisms controlling maternal insulin resistance and fetal growth in pregnancy and may provide a foundation for the development of strategies aimed at improving adiponectin production in pregnant women with obesity or gestational diabetes.

physiology↗