This article was contributed by Megan Lee

If you feel like you’ve been seeing more pregnant women lately, your eyes are not deceiving you. According to the US Census, August is the month with the highest number of births.  During pregnancy, the fetus relies on its mother’s diet to sustain its nutritional needs for growth and development in the womb. For years, scientists have studied the potential long-term effects of prenatal nutrition on the development of adult diseases like hypertension, cardiovascular disease, and diabetes. New research is showing that a mother’s nutrition and health may also contribute to permanent changes in fetal metabolism, even before she knows she’s eating for two.

The Basics of Reproductive Physiology and Early Nutrition

The full-term human fetus develops from a single cell and needs nutrition from the moment of conception. The developing fetus relies primarily on the mother’s placenta for energy, but it takes nearly 12 weeks until growth of the placenta is complete. How are the high-energy needs of a growing baby fueled from day one?

Upon ovulation, a mature female egg (ovum) is released into the fallopian tube. Fertilization takes place within the fallopian tube when a sperm meets the egg, forming a single-celled zygote.  Over the next several days, the zygote divides rapidly while traveling to the uterus, relying on energy stored in the egg to fuel its growth. By the time it reaches the uterine cavity, the shape of the cell mass has changed from a solid sphere to a more ring-like shape with an inner cell mass called the blastocyst. The developing blastocyst remains in the uterine cavity for 4-5 days before implanting in the uterine lining (endometrium), using nutrients from endometrial secretions to meet its energy needs until implantation occurs. The outer cells of the blastocyst, or trophoblast, are the first cells to differentiate and take on specialized tasks. Its first task is to initiate implantation by secreting enzymes that help break down the cells of the endometrium. The trophoblastic cells digest endometrial cells, absorbing the nutrients and transferring them to the blastocyst to provide further sustenance. While some trophoblastic cells break down the endometrium for nutrition, others form cords of cells that reach deeper into the endometrium to allow the blastocyst to attach and implant. Once implantation is complete, around one week post ovulation, the trophoblast and cells from the endometrium proliferate rapidly to form the placenta. The endometrium is the only source of nutrients for the embryo in the first week of implantation and remains a major source of nutrition for 8-12 weeks until the development of the maternal blood supply to the placenta is complete.

The Roots of the ‘Fetal Origins of Disease’ Theory

In the late 1980s and early 1990s, David Barker, an epidemiologist, and his colleagues at the University of Southampton published a series of groundbreaking studies that found an association between low-birthweight and adult chronic diseases. Barker’s hypothesis posits that malnutrition, even subclinical malnutrition, can adversely affect growth of the fetus.  An infant born with a low-birthweight has presumably developed more slowly in the womb.  Barker’s studies showed that low-birthweight infants have higher incidences of chronic diseases such as coronary heart disease, type-2 diabetes, hypertension, and stroke as adults.

The connection between low-birthweight and type-2 diabetes is attributed to what Barker calls the “thrifty phenotype”. He hypothesizes that a malnourished fetus adapts its metabolism to a low-nutrient environment in the womb.  If that infant is then exposed to an environment of caloric excess during childhood, as is the case in many developed countries, excess nutrients are stored as fat instead of muscle, and this altered body composition can eventually lead to obesity and insulin resistance in adulthood.  This hypothesis rests on the assumption that our metabolisms are “hard-wired” during fetal development, and that these systems are therefore unable to adapt to a different degree of food availability during childhood and beyond.

The notion that prenatal nutrition could be linked to adult health, dubbed the developmental origins of disease theory, was astounding to the medical and research community at the time. There were many skeptics of his early research, but further studies have continued to show this pattern of birthweight being correlated with adult metabolic disease.

New Research on Prenatal Nutrition and its effect on the Fetal Environment

Barker’s hypothesis is no longer considered controversial, but the mechanism of how maternal nutrition influences long-term health outcomes is still being examined. Last month at the Society for Reproductive Science conference in Pittsburg, PA, new research proposed some explanations for how prenatal nutrition might influence adult health, and highlighted the role of prenatal nutrition at even the very early stages of pregnancy.

Researchers are finding that nutrition for the blastocyst and even the single-celled zygote may be especially critical. A group of scientists led by Kelle Moley from Washington University has discovered that in mouse studies, the nutritional environment at the zygote stage can produce long-term effects in the developing fetus. The researchers transferred single-celled zygotes from diabetic mice into non-diabetic mice.  They found that, compared to normal mice, the zygotes from the diabetic mice had higher rates of growth defects later in fetal development, including neural tube defects, heart defects, and limb deformities.  Because the embryos were transferred at the zygote stage, this suggests that maternal nutrition even before this point is important for the health of the offspring.  The researchers hypothesize that the high blood sugar of diabetics may cause changes in the mothers’ eggs themselves that eventually lead to changes in a fetus if an egg becomes fertilized, though this will take many more studies to fully investigate.

Another scientist, Tom Fleming from the University of Southampton, presented a mouse study displaying the so-called thrifty phenotype. His team fed mice a low-protein diet during the stages before implantation, followed by normal nutrition for the rest of gestation and postnatally. Mice that were fed a diet low in protein had offspring that were heavier than the controls and showed signs of cardiovascular abnormalities and hypertension as adult mice. Fleming’s lab analyzed a selection of embryos from both mice and found differences in cell development during the early blastocyst stage that eventually produced changes in the trophoblast when these outer cells differentiated. Because the trophoblast plays a significant role in the development of the fetal side of the placenta, this research suggests that the diet programs the offspring’s metabolism early on. The zygote and blastocyst seem to sense a low-nutrient environment, so they boost metabolism to collect as many nutrients as possible during pregnancy, presumably to compensate for the potentially low-nutrient environment outside the womb. After the mice are born, they still show this type of metabolism that promotes nutrient storage in the form of fat.

It’s not just undernutrition that affects long-term changes: both animal and human studies show that obesity during pregnancy can also affect fetal metabolism, though more studies need to be done on the cellular and molecular level to examine how this happens. Preliminary research shows that offspring of obese mothers tend to show insulin resistance and have decreased functioning of the pancreas: their pancreases produce lower amounts of several hormones necessary for metabolism. These offspring also had higher rates of developmental anomalies similar to those of diabetic mothers such as neural tube defects, abnormalities in the functioning of arteries, and increased susceptibility to high blood pressure.

Barker’s work, the studies described above, and work by many other researchers, has established that the nutritional environment during early gestation influences adult metabolism.  But exactly how, at the molecular level, are these changes mediated?  One potential mechanism by which nutrients can influence metabolism is through changes in gene expression, or the amount or type of protein made from a particular gene. The amount and type of products made from genes define how cells in the body function. While differences in gene expression can be hereditary, they can also be due to factors in the environment like nutrient availability. While these studies suggest that this is indeed occurring, what is exactly happening at the genetic level still needs to be examined.

The role of maternal nutrition seems well-established, but what about the paternal nutrition? While the father’s nutrition has been examined for its role in infertility, it has not been studied extensively for its influence in embryonic development.

Life-style or Fetal Origins of Disease?

Scientific evidence suggests that adult metabolic diseases may be the result of the nutritional environment both before conception and throughout gestation.  But we shouldn’t point fingers at moms just yet. Prenatal nutrition is just one factor among many that may influence human development and metabolism. It is clear that adult lifestyle factors such as smoking, diet, and exercise also contribute to chronic disease risk.  Thus, metabolic disease is likely caused by a combination of prenatal development and adult lifestyle factors.  Maintaining a healthy weight and eating a nutritious diet with complete vitamins and minerals is therefore important for mothers, fathers, and children alike.

For more information, please see:

University of Pittsburgh Schools of the Health Sciences (2009, July 22). Are We What Our Mothers Ate?. ScienceDaily.­ /releases/2009/07/090721122843.htm

Mitchell, MK. Nutrition Across the Lifespan. Philadelphia: Elsevier. 2003

Primary research referenced in this article:

Moley KH. Too Much of a Sweet Thing–Maternal Diabetes and Oocyte Quality. Biol Reprod 81: 2.

Wyman A, Pinto AB, Sheridan R, and Moley KH. One-Cell Zygote Transfer from Diabetic to Nondiabetic Mouse Results in Congenital Malformations and Growth Retardation in Offspring. Endocrinology 2008 February; 149(2): 466–469.