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Maternal Hyperhomocysteinemia Compromises Female Offspring Fertility Through Over-Activation of Primordial Follicles

ABSTRACT: Hyperhomocysteinemia (HHcy), characterized by elevated plasma homocysteine levels exceeding 15 µmol/L, has been associated with various issues impacting personal health and offspring's well-being. This study examines the impact of maternal HHcy, induced by a high-methionine diet, on the fertility of female offspring mice. The results showed that maternal HHcy caused the over-activation of primordial follicles in female offspring mice by promoting the phosphorylation of key factors, including RPS6, MTOR, FOXO3A, and AKT. Meanwhile, the number of mitochondria in mature oocytes decreases, and mitochondrial function declines, further leading to an increase in reactive oxygen species (ROS) levels, an increase in the proportion of DNA damage, and spindle abnormalities, ultimately impairing the quality of oocytes. These findings demonstrate that maternal HHcy decreases offspring fertility by inducing primordial follicle over-activation and impairing oocyte quality. This provides new insights into the pathological mechanisms of HHcy affecting offspring's reproductive potential.

ORGANISM(S): Mus musculus

PROVIDER: GSE322825 | GEO | 2026/05/18

REPOSITORIES: GEO

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Project description:Slimming is globally prevalent especially in young women, and it may contribute to the metabolic health of their offspring. Whereas some Lamarckian ideas about environmental inheritance have been dismissed, increasing evidence suggest that certain acquired traits can be transmitted to the next generation. It is therefore of great interest to determine how and to what extent a maternal lifestyle change contributes to their offspring. Here we show that enriched environment (EE) induced maternal slimming improves general health and reprograms metabolic gene expression in mice offspring. EE in mothers induced decreased body weight, adiposity, and improved glucose tolerance and insulin sensitivity. Relative to controls, their offspring exhibited improved general health such as reduced fat accumulation, enhanced metabolic parameters as well as glucose tolerance and insulin sensitivity. Maternal slimming altered the expression of 1,732 genes in the liver of offspring, with coherent downregulation of genes involved in lipid and cholesterol biosynthesis. Epigenomic profiling in offspring revealed numerous changes in cytosine methylation depending on maternal slimming, including hypermethylation of several genes involved in lipid biosynthesis, correlated with the downregulation of these genes. Maternal slimming also altered overall transcriptome patterns in mature oocytes, which contributes largely to the metabolic health and gene expression patterns in offspring. Overall, our studies suggest that maternal slimming have a beneficial role in regulating metabolic profiles in offspring, implying that it might be considered as a potential strategy to reverse the global prevalence of obesity and related metabolic syndromes. Examination of the effect of 2 different maternal lifestyles, control and slimming, on the mRNA expression in the mature oocytes of the female mice. Naturally ovulated mature oocytes (MII stage) were collected from 3 control and 3 slimming female F0 founders (3 oocytes per mouse, 9 oocytes for each group).

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Maternal Hyperhomocysteinemia Compromises Female Offspring Fertility Through Over-Activation of Primordial Follicles

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