Importance of Windows of Exposure to Maternal High-Fat Diet and Feto-Placental Effects: Discrimination Between Pre-conception and Gestational Periods in a Rabbit Model.

Delphine Rousseau-Ralliard,Gwendoline Morin,Nathalie Daniel,Catherine Rey,Michèle Dahirel,Jérémy Bertrand,Anne Couturier-Tarrade,Audrey Prézelin,Pascale Chavatte-Palmer,Marie-Christine Aubrière

doi:10.3389/fphys.2021.784268

Abstract

Context and Aim: Lipid overnutrition in female rabbits, from prepuberty, leads to impaired metabolism (dyslipidemia and increased adiposity) and follicular atresia, and, when continued during gestation, affects offspring phenotype with intrauterine growth retardation (IUGR) and leads to placental and lipid metabolism abnormalities. Growth retardation is already observed in embryo stage, indicating a possible implication of periconceptional exposure. The objective of this study was to discriminate the effects of preconception and gestational exposures on feto-placental development.Materials and Methods: Rabbit 1-day zygotes were collected from female donors under control (CD) or high-fat-high-cholesterol (HD) diet and surgically transferred to the left and right uterus, respectively, of each H (n = 6) or C (n = 7) synchronized recipients. Close to term, four combinations, CC (n = 10), CH (n = 13), HC (n = 13), and HH (n = 6), of feto-placental units were collected, for biometry analyses. Fatty acid (FA) profiles were determined in placental labyrinth, decidua, fetal plasma, and fetal liver by gas chromatography and explored further by principal component analysis (PCA). Candidate gene expression was also analyzed by RT-qPCR in the placenta and fetal liver. Data were analyzed by Kruskal–Wallis followed by Dunn’s pairwise comparison test. Combinations of different data sets were combined and explored by multifactorial analysis (MFA).Results: Compared to controls, HH fetuses were hypotrophic with reduced placental efficiency and altered organogenesis, CH presented heavier placenta but less efficient, whereas HC presented a normal biometry. However, the MFA resulted in a good separation of the four groups, discriminating the effects of each period of exposure. HD during gestation led to reduced gene expression (nutrient transport and metabolism) and big changes in FA profiles in both tissues with increased membrane linoleic acid, lipid storage, and polyunsaturated-to-saturated FA ratios. Pre-conception exposure had a major effect on fetal biometry and organogenesis in HH, with specific changes in FA profiles (increased MUFAs and decreased LCPUFAs).Conclusion: Embryo origin left traces in end-gestation feto-placental unit; however, maternal diet during gestation played a major role, either negative (HD) or positive (control). Thus, an H embryo developed favorably when transferred to a C recipient (HC) with normal biometry at term, despite disturbed and altered FA profiles.

Highlights

The incidence of obesity and overweight has reached epidemic levels in the United States, Europe, and other developed countries worldwide (Ng et al, 2014)
Fetal length was significantly increased in the CH fetuses compared to controls, but CH placental efficiency was decreased, with significantly heavier placenta and decidua
The fatty acids (FAs) profiles or gene expression in HC were not significantly different from Compared to controls (CC), when we studied these different datasets separately, in this multiple factor analysis (MFA), this HC group appeared completely dissociated from CC, demonstrating that the fetal repercussions of the preconception environment deserved to be studied because it affects, beyond the placenta, the fetus health as well

Summary

Introduction

The incidence of obesity and overweight has reached epidemic levels in the United States, Europe, and other developed countries worldwide (Ng et al, 2014). Caused by food transition and changes in dietary behavior (over-nutrition of industrialized food), this metabolic status is associated with a major risk of developing serious diet-related non-communicable diseases, such as type-2 diabetes, cardiovascular disease, hypertension, and stroke, that are often associated with non-alcoholic fatty liver disease and reduce the overall quality of life and overall lifespan. Excess body weight reduces fertility and increases obstetric complications, such as miscarriage, gestational diabetes, hypertension, pre-eclampsia, and difficult delivery (LangleyEvans, 2009). Children born to obese or overweight mothers have increased adiposity and are at higher risk of metabolic diseases later (Mitanchez and Chavatte-Palmer, 2018). The specific effect of preconception over-nutrition has been less studied (Fleming et al, 2004; Kwong et al, 2006), there is clear evidence from animal and a limited number of human studies that body composition and nutrient supply during these periods may impact fertility and early embryo viability (Shankar et al, 2008; Watkins et al, 2008; Lane et al, 2015; Stang and Huffman, 2016; Yang et al, 2021) as well as induce long-term metabolic effects on offspring (Satpathy et al, 2008; Smedts et al, 2008; Wax, 2009; Stephenson et al, 2018; Panchenko et al, 2019)

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