Diet before and during Pregnancy and Offspring Health: The Importance of Animal Models and What Can Be Learned from Them

Abstract

This review article outlines epidemiologic studies that support the hypothesis that maternal environment (including early nutrition) plays a seminal role in determining the offspring's long-term health and metabolism, known as the concept of Developmental Origins of Health and Diseases (DOHaD). In this context, current concerns are particularly focused on the increased incidence of obesity and diabetes, particularly in youth and women of child-bearing age. We summarize key similarities, differences and limitations of various animal models used to study fetal programming, with a particular focus on placentation, which is critical for translating animal findings to humans. This review will assist researchers and their scientific audience in recognizing the pros and cons of various rodent and non-rodent animal models used to understand mechanisms involved in fetal programming. Knowledge gained will lead to improved translation of proposed interventional therapies before they can be implemented in humans. Although rodents are essential for fundamental exploration of biological processes, other species such as rabbits and other domestic animals offer more tissue-specific physiological (rabbit placenta) or physical (ovine maternal and lamb birth weight) resemblances to humans. We highlight the important maternal, placental, and fetal/neonatal characteristics that contribute to developmentally programmed diseases, specifically in offspring that were affected in utero by undernutrition, overnutrition or maternal diabetes. Selected interventions aimed at prevention are summarized with a specific focus on the 1000 days initiative in humans, and maternal exercise or modification of the n-3/n-6 polyunsaturated fatty acid (PUFA) balance in the diet, which are currently being successfully tested in animal models to correct or reduce adverse prenatal programming. Animal models are essential to understand mechanisms involved in fetal programming and in order to propose interventional therapies before they can be implemented in humans. Non-rodent animals are particularly important and should not be neglected, as they are often more physiologically-appropriate models to mimic the human situation.

Keywords: 1000 days; DOHaD; fetal programming; rodent and non-rodent animal models.

Figure 1

Schematic representation of the DOHaD (developmental origins of health and diseases) concept in human beings, showing the effects of several maternal conditions (non exhaustive) during the gestation on feto-placental unit development (affected parameters), leading to particular birth size from SGA (small for gestational age) to LGA (large for gestational age), and the most observed outcomes in terms of health at adulthood.

Figure 2

Schematic representation of materno-fetal vascularization in human normal pregnancy or preeclampsia conditions leading to intrauterine growth retardation (IUGR).

Figure 3

Schematic representation of prevalent models for studying exposures to maternal nutrition or metabolism during gestation, the consecutive and species-specific birth size, and the usual outcomes in terms of health for all animal models at adulthood. One color is attributed to each kind of exposure: red for placental insufficiency and maternal malnutrition (undernutrition), green for over nutrition, orange for obesity and purple for diabetes. The column “size at birth” gave the fetal response to each kind of maternal conditions in term of size compared to control conditions in the same species. The same color is used for the “small” or “normal” or “large” response to each corresponding maternal conditions compared to normal (or expected) size for same age in the same species.