Abstract
Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.
Highlights
Over the past 30 years, obesity in males in the reproductive age has tripled, concomitant with the increase in male infertility [1]
To identify Long non-coding RNAs (lncRNAs) and mRNAs that are differentially expressed in mice sperm between the obese and normal groups, we carried out microarray analysis of lncRNA and mRNA expression in F0-high fat diet (HFD) and F0
In order to reveal the impact of obesity induced by a high-fat diet on progeny fertility, we examined the expression of lncRNA and mRNA in the spermatozoa of obese and normal mouse offspring
Summary
Over the past 30 years, obesity in males in the reproductive age has tripled, concomitant with the increase in male infertility [1]. Obesity can have a negative impact on male reproductive potential by reducing sperm density and motility [2, 3] and increasing the release of reactive oxygen species (ROS), which can cause DNA damage and influence plasma membrane integrity in sperm [4, 5]. Male offspring from high fat diet (HFD) fathers have a high sensitivity to HFD-induced metabolic and reproductive disturbances [6]. Genetic and epigenetic changes in the spermatozoa may explain paternal programming www.impactjournals.com/oncotarget of offspring phenotypes induced by paternal obesity [7]. DNA methylation is required for spermatogenesis, and it has been demonstrated that diet-induced paternal obesity regulates germ cell methylation status and causes metabolic disorders in two generations of mice [11, 12]. Paternal obesity changes the expression of insulin-like growth factor 2 (IGF2) in infants by influencing normal IGF2 methylation in spermatozoa [13]. The contribution of the patrilineal phenotype to fertility is not just at the DNA level [14]; sperm RNA can reflect the quality of spermatogenesis, and its fertilizing capacity and post-fertilisation functions [15]
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