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The Role of Feed Restriction on DNA Methylation, Feed Efficiency, Metabolome, Biochemical Profile, and Progesterone Patterns in the Female Filial Generation (F1) Obtained From Early Feed Restricted Ewes (F0).

ABSTRACT: Deficient management of replacement animals in the farm during early developmental windows may promote adverse programming effects on reproductive traits and subsequent transmission to the next generation. In this sense, DNA methylation profiles allow researchers to decode epigenetic regulation mechanisms in mammals and identify novel candidate genes correlated with phenotype differences in both dams and offspring. Therefore, improving knowledge in the field of epigenetics and intergenerational effects caused by prenatal and postnatal early nutritional events (e.g., feed restriction) is crucial for refining strategies dedicated to animal breeding. In this study, we determined differences in the global blood methylation patterns, biochemical profile, and metabolome of ewe lambs (F1) born from either early feed restricted dams (F0-RES) or fed ad libitum (F0-ADL). Our data show that functional categories such as those related to cellular processes, phosphorylation, nervous system, immunity response, or reproductive function were enriched significantly in the F1-RES lambs due to differences in the methylation of genes in these categories. These F1-RES lambs did not show differences in feed efficiency during the replacement period but presented higher levels of insulin and triglycerides and reduced concentration of progesterone, whereas the metabolome profile demonstrated variations in the bile acid composition when compared with the F1-ADL lambs. Taken together, all these results suggest that intergenerational effects caused by early feed restriction of dams (F0) may persist in the F1 female lambs with negative consequences on genes involved in cellular processes and reproductive traits.

SUBMITTER: Andres S

PROVIDER: S-EPMC8745145 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Feed restriction during the early life of ewe lambs (F0) triggers the transfer of epigenetic marks to the next generation, thus impairing the reproductive performance of F1. However, the effects of this factor on milk production and composition, including its abundance in regulatory miRNA (many of which are contained in exosomes, small vesicles of endocytic origin that play a role in the modulation of immune response of the offspring), has not been tested so far. Therefore, in this study, the replacement ewe lambs (F0) obtained in a previous project (a group of ewes fed milk replacer ad libitum –ADL– vs. a group of ewes restricted –RES– to 62.5% the intake level of milk replacer during the suckling period) were raised under similar post-weaning conditions and mated to obtain the progeny (F1). The F1 dairy ewes were also mated, and six of these F1 dairy ewes were selected and divided into two groups: the F1-ADL group (n=3) born from F0-ADL and the F1-RES group (n=3), born from F0-RES animals. Milk production was controlled during the peak lactation period, and milk samples were obtained for each gland separately to measure chemical composition, somatic cell counts, and bacteriology. Exosomes were also isolated for each gland separately to define the miRNA content. The miRNAome was determined following a Next Generation Sequencing approach. The first preliminary results indicate significant differences in the abundance of five miRNAs in the milk obtained during the peak of lactation. Thus, oar-miR-150, oar-miR-221, oar-miR-23a, oar-miR-27a, oar-miR-376c were all down modulated in F1-RES when compared to F0-ADL. Most of these miRNAs have been found to play a role in biological functions such as development, apoptosis, muscle differentiation, reproduction, or milk production. Moreover, somatic cell count (SCC) was reduced significantly in milk samples during the peak of lactation of F1-RES dairy sheep. No significant differences were found in milk production, the chemical composition of milk (fat, protein, lactase), or bacteriology (colony forming units, CFU). This study's results provide some evidence of the effects of nutritional programming events on the milk's bioactive components.

Project description:A negative energy balance (NEB) is detrimental to reproduction in animals. A suggested link between NEB and reproductive failure is the gastrointestinal hormone ghrelin, because of the association between ghrelin and the hypothalamo-pituitary-gonadal axis. The [D-Lys3]-Growth Hormone Releasing Peptide-6 ([D-Lys3]-GHRP-6) is a ghrelin antagonist that acts on ghrelin receptors (GHS-R1). The objective of this study was to evaluate the effect of [D-Lys3]-GHRP-6 on reproduction variables in feed restricted ewes. Two experiments were conducted. Experiment I was conducted for 30 days; and Experiment II for 13 days. In both experiments the ewes (n = 18) were randomly assigned to: Control (CO): fed to meet maintenance requirements; Feed restriction (FR): 80% of maintenance restriction; or Ghrelin antagonist (GA): feed restricted and daily subcutaneous of 7.5μg/kg of [D-Lys3]-GHRP-6. Plasma was collected to measure hormones and metabolite concentration. In Experiment II, the hypothalamus and ovaries were collected on day 13. In both Experiments, sheep allocated to the FR and GA treatments decreased their body weight compared with sheep in the CO group (P < 0.06); progesterone however, did not differ between treatments (P > 0.10). Experiment I: Plasma ghrelin concentration was greater (P < 0.01) in FR and GA compared with CO ewes. Plasma non-esterified fatty acids concentration was greater (P < 0.01) in GA and FR than CO. Experiment II: Kisspeptin1-Receptor (Kiss1-R) mRNA expression was greater in FR (P < 0.01) and tended to be greater in GA (P = 0.10) compared with CO ewes. The neuro peptide-Y (NPY) mRNA expression was greater (P = 0.03) in FR than CO; and tended to be greater (P = 0.06) compared with GA ewes. Growth hormone releasing hormone (GhRH) mRNA expression was greater in GA (P = 0.04) and tended to be greater in FR (P = 0.07) compared with CO ewes. Feed restriction increased GhRH, NPY, and Kiss-R mRNA expression in hypothalamus without affecting reproductive variables.Ghrelin antagonist may prevent an increase inNPY expression in ewes.

Project description:The objective of this study was to evaluate the changes in the ruminal fermentation, epithelium-associated microbiota, and ruminal epithelial barrier function in response to severe feed restriction (SFR) in pregnant ewes. Sixteen pregnant ewes (108 d of gestation) were randomly blocked and assigned to 1 of 2 treatments: control (CON, n = 8) and SFR (n = 8). Ewes were fed a common diet with a 60:40 forage to concentrate ratio for 7-d baseline period followed by a SFR challenge period. Ewes on the SFR treatment were restricted to 30% of the base for 15 d. At the end of the experimental period, all animals were slaughtered and then ruminal contents and ruminal epithelial tissue were collected. Results showed that ruminal pH was greater in SFR group (P = 0.040) compared with CON group, while SFR decreased (P < 0.05) the concentrations of ruminal acetate, propionate, butyrate, and total volatile fatty acid. A plot of principal coordinate analysis and analysis of molecular variance revealed that the composition of ruminal epithelial bacterial communities in the CON group was distinct from that of the ruminal epithelial microbiome in the SFR animals. At the genus level, SFR increased the abundance of unclassified Neisseriaceae, Comamonas, and Papillibacter, and decreased the proportion of Howardella, Desulfobulbus, and Suttonella (P < 0.05) compared with CON group. The metagenome of ruminal epithelium-associated microbiota predicted by PICRUSt revealed that the SFR significantly affected 14 metabolic pathways, and 9 were significantly enriched in the SFR group. In particular, SFR markedly increased relative abundances of dominant gene families involved in amino acid metabolism (P = 0.003), cellular processes and signaling (P = 0.021), and lipid metabolism (P = 0.001). The real-time PCR results showed SFR decreased the mRNA expression of IL-10 (P = 0.003) and upregulated the mRNA expression of IL-6 (P = 0.003) and TLR4 (P = 0.021). The mRNA expression of Claudin-1 (P = 0.001) and ZO-1 (P = 0.009) were lower in the SFR group compared with the CON group. Generally, our data suggest that SFR decreased most ruminal fermentation parameters, altered the composition of rumen epithelium-associated microbiota, and compromised the barrier function of rumen epithelium. These findings are of great importance for understanding the alteration in the rumen function following SFR in pregnant ewes.

Project description:Paternal high-fat diet (HFD) can alter the epigenetics of sperm DNA, resulting in the transmission of obesity-related traits to the offspring. Previous studies have mainly focused on the HFD-induced changes in DNA methylation of imprinted genes, overlooking the potential involvement of non-imprinted genes in this process. SETD2, an important epigenetically-regulated gene known for its response to environmental stress, remains poorly understood in the context of high-fat diet-induced epigenetic changes. Here we examined the effect of obesity from a HFD on paternal SETD2 expression and methylation in sperm, and embryos at the blastocyst stage and during subsequent development, to determine the alteration of SETD2 in paternal intergenerational and transgenerational inheritance. The result showed that mice fed with HFD for two months had significantly increased SETD2 expression in testis and sperm. The paternal HFD significantly altered the DNA methylation level with 20 of the 26 CpG sites being changed in sperm from F0 mice. Paternal high-fat diet increased apoptotic index and decreased total cell number of blastocysts, which were closely correlated with DNA methylation level of sperm. Out of the 26 CpG sites, we also found three CpG sites that were significantly changed in the sperm from F1 mice, which meant that the methylation changes at these three CpG sites were maintained. In conclusion, we found that paternal exposure to an HFD disrupted the methylation pattern of SETD2 in the sperm of F0 mice and resulted in perturbed SETD2 expression. Furthermore, the paternal high-fat diet influenced embryo apoptosis and development, possibly through the SETD2 pathway. The altered methylation of SETD2 in sperm induced by paternal HFD partially persisted in the sperm of the F1 generation, highlighting the role of SETD2 as an epigenetic carrier for paternal intergenerational and transgenerational inheritance. Supplementary Information The online version contains supplementary material available at 10.1186/s12263-023-00731-4.

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The Role of Feed Restriction on DNA Methylation, Feed Efficiency, Metabolome, Biochemical Profile, and Progesterone Patterns in the Female Filial Generation (F1) Obtained From Early Feed Restricted Ewes (F0).

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