Endocrine Abstracts

Periconceptional low-protein (LPD) intake has been linked to altered developmental trajectory of offspring, increasing their risk of developing non-communicable diseases in adulthood. These effects have been attributed to changes in the parental 1-Carbon metabolism. Until now, effects of poor maternal or paternal diet have been investigated individually and not in combination, despite being of higher clinical relevance. This study aimed to investigate the combined impact of maternal and paternal LPD on parental 1-C metabolism and preimplantation embryo development. Eight-week-old C57BL/6 mice were fed either a normal protein diet (NPD; 18% casein) or LPD (9% casein) for 8 weeks. Mice were mated in a 2×2 factorial design, resulting in four dietary groups: NN (NPD female, NPD male), NL (NPD female, LPD male), LN (LPD female, NPD male) and LL (LPD female, LPD male). Females were culled at embryonic day 1.5 (E1.5) for preimplantation embryo collection and culture in a time-lapse system (EmbryoScope). Liver 1-C metabolites were analysed using a novel LC-MS/MS method. A significant interaction between maternal and paternal diets was observed for blastocyst morphology, with embryos from group LL (both parents on LPD) showing a 20% decrease in survival rate. Maternal livers showed reduced ADMA, betaine, glycine, and serine, with increased cysteine and SAM, while methionine remained unchanged. Paternal livers exhibited lower choline and methionine, with no change in SAM. Branched-chain amino acids (valine, leucine) were significantly reduced in both maternal and paternal tissues. These findings indicate that parental LPD disrupts key metabolic pathways in both maternal and paternal tissues, particularly amino acid availability and methylation-related metabolites, which likely contribute to impaired blastocyst morphology and reduced embryo survival. The results highlight the synergistic impact of maternal and paternal nutrition on early embryonic development and emphasise the critical importance of adequate parental protein intake for reproductive success and developmental programming.