inducing maternal dietary deficiencies in mice to study the impact on offspring health

Effect of Maternal Folic Acid and Choline Deficiencies on Offspring Health

Maternal nutrition during pregnancy and lactation plays a vital role in offspring development. One-carbon (1C) metabolism is a key metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. Folic acid and choline are central components of 1C that play an important role in the closure of the neural tube. It is widely recommended for women to supplement with folic acid and choline during their childbearing years1. While the critical role of folic acid in fetal development is clearly established, the underlying mechanisms involved remain unclear. Women of childbearing are recommended to take folic acid prior to becoming pregnant since the closure of the neural tube occurs within the first trimester2. Pregnant mothers who are deficient in folic acid or other components of 1C, like choline, have a higher incidence of birthing offspring with neural tube defects due to the high demand for nucleotide synthesis and other processes required by the early gestational period3.
The long-term impact of maternal diets deficient in 1C metabolism intake on offspring health outcomes is poorly understood. Research from our laboratories, as well as others, has demonstrated that maternal diets deficient in either folic acid or choline do indeed impact offspring health outcomes after ischemic stroke using preclinical models4,5,6. The impact of maternal diet has also been shown in clinical studies where smaller brain volumes and altered methylation levels have been described7. The Developmental Origins of Health and Disease (DOHaD) theory suggests that prospective chronic diseases are programmed in utero8,9, and maternal diet plays an important role.
This protocol is designed to outline the method for altering 1C dietary consumption in female mice before pregnancy, with the purpose of examining the effects of maternal nutrition on the health outcomes of the offspring.

Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes

We are interested in understanding how maternal dietary deficiencies in folic acid or choline during pregnancy and lactation impact long-term offspring health outcomes. We know that folic acid is really important for the closure of the neural tube in utero, but my laboratory is interested in what roles it plays after birth. We are reading studies that are showing that maternal diet during pregnancy and lactation does play an important role in offspring health.Dietary changes include high fat, one carbon metabolism, et cetera. These changes are sometimes seen in several generations of offspring. We are using a variety of tools to understand the long-term effects on offspring that come from moms with dietary deficiencies in folate and choline.Our most recent study is looking at metabolite changes in stool samples of offspring. We use behavioral neuroscience, biochemical assays, molecular biology, and epigenetic tools. My research group is the first one to show that maternal dietary deficiencies in either folic acid or choline during pregnancy and lactation result in worse stroke outcome for female and male offspring.We are really interested in understanding the long-term role that maternal dietary deficiencies in either folic acid or choline have on offspring health outcomes. Folic acid is well known for its role in the closure of the neural tube in utero. The impact of deficiencies after birth on brain function are not well-defined.

Inducing Maternal Dietary Deficiencies in Mice to Study the Impact on Offspring Health

To begin, obtain folic acid or choline-deficient feed from commercial rodent food manufacturers. The special diet contains 0.3 milligrams per kilogram of folic acid, or 300 milligrams per kilogram of choline by tartrate. Maintain a female mouse on this special diet for four to six weeks.Later, when the offspring are weaned from the mother, Place them on a folic acid or choline-deficient diet as well as a control diet. After euthanizing the offspring, collect the blood sample and liver tissue for biochemical analysis. Add the blood to an EDTA-coated tube and centrifuge the tube to isolate the blood plasma for determining the concentration of one-carbon metabolites.Then, transfer the cut liver tissue samples into a cryo-storage tube for snap freezing. The baseline and weekly weights of female mice on control, choline, or folic acid-deficient diets during the four weeks before mating showed no significant difference. The maternal one-carbon metabolite concentrations were slightly low in the plasma of mice subjected to folic acid-deficient diet as compared to the control mice.

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Research

JoVE Journal

Neuroscience

63 Views. To begin, obtain folic acid or choline-deficient feed from commercial rodent food manufacturers. The special diet contains 0.3 milligrams per kilogram of folic acid, or 300 milligrams per kilogram of choline by tartrate. Maintain a female mouse on this special diet for four to six weeks.Later, when the offspring are weaned from the mother, Place them on a folic acid or choline-deficient diet as well as a control diet. After euthanizing the offspring, collect the blood sample and liver ...

Video: Inducing Maternal Dietary Deficiencies in Mice to Study the Impact on Offspring Health

Maternal nutrition during pregnancy and lactation plays an important role in the neurodevelopment of offspring. One-carbon (1C) metabolism, which centers around folic acid and choline, as well as other B vitamins, plays a key role during the closure of the neural tube of the developing fetus. However, the impact of these maternal nutritional deficiencies during pregnancy on offspring health outcomes after birth remains relatively undefined. Furthermore, maternal dietary deficiencies in folic acid or choline may impact other health outcomes in offspring - making this a valuable model. This protocol aims to outline the procedure for inducing a deficiency in 1C metabolism in female mice through dietary modifications. Females are placed on diets at weaning, up to 2 months of age, for 4-6 weeks prior to mating and remain on diet throughout pregnancy and lactation. Offspring from these females can be evaluated for health outcomes. Females can be used multiple times to generate offspring, and tissues from females can be collected to measure for 1C metabolite measurements. This protocol provides an overview of how to induce maternal dietary deficiencies in folic acid or choline to study offspring health outcomes.

This protocol describes the method for reducing dietary intake of folic acid or choline in female mice prior to pregnancy with the objective of investigating the impact of maternal diet on offspring health outcomes.

Maternal nutrition during pregnancy and lactation plays an important role in the neurodevelopment of offspring. One-carbon (1C) metabolism, which centers ...