The effect of high-fat diet during mouse preimplantation and pregnancy-lactation on uterine fluid protein composition, maternal metabolism and offspring health

Abstract

Optimal nourishment during pregnancy is required for the proper development of offspring. The increase in high-fat diet (HFD) consumption, particularly among reproductive-age women, has been associated with obesity. Previous studies have shown that exposure to maternal HFD during critical periods such as preimplantation and pregnancy increases the risk of metabolic syndrome-related illnesses in offspring. In this study using mice, we investigated the hypothesis that maternal HFD, in the absence of obesity, during the preimplantation period alone or during gestation/lactation, induces metabolic changes in mothers and alters uterine fluid (UF) and serum protein composition during preimplantation, subsequently affecting offspring metabolism.
Female MF1 mice were mated and allocated to different diets from conception: Control-Fat Diet (CFD, standard diet with 7% fat), Embryonic-HFD (EmbHFD, HFD with 45% fat until day 3.5 of pregnancy, then standard diet), or HFD (HFD throughout gestation and lactation). After weaning, all the offspring were maintained on the standard diet. An Additional cohort was used to study serum and UF protein composition using nano-liquid chromatography-tandem mass spectrometry, as well as metabolic changes in dams on embryonic day 3.5 (E3.5).
Our findings demonstrated altered protein expression in serum and UF in dams exposed to HFD at E3.5. Furthermore, gene expression related to lipid metabolism in the uterus and liver was altered in dams during the preimplantation period. Leptin and cholesterol serum concentration were also affected in dams exposed to HFD during the preimplantation and pregnancy/lactation. Offspring mice exposed to maternal HFD (in the absence of obesity) displayed metabolic disturbances. EmbHFD and HFD offspring exhibited higher systolic blood pressure (SBP), elevated cholesterol and leptin concentrations in serum, and alterations in fatty acid profiles. Energy metabolism analysis revealed significant differences in energy expenditure (EE) and respiratory exchange ratio (RER) in HFD offspring. These physiological observations were corroborated by altered metabolic gene expression in brown adipose tissue (BAT), particularly among EmbHFD and HFD female offspring. Additionally, lipid accumulation in skeletal muscle was significantly different, and EmbHFD and HFD offspring exhibited reduced resistance on the rotarod.
Our study demonstrates, for the first time, that poor maternal nutrition during the preimplantation affects UF and serum protein composition, as well as maternal metabolism, which can subsequently impact offspring physiology and metabolism, despite adequate nutrition.

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Identifiers

ORCID for Irene Peral Sanchez: orcid.org/0000-0001-9725-3036

ORCID for Sandrine Willaime-Morawek: orcid.org/0000-0002-1121-6419

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