Embryo Project Encyclopedia Articles

Fetal programming, or prenatal programming, is a concept that suggests certain events occurring during critical points of pregnancy may cause permanent effects on the fetus and the infant long after birth. The concept of fetal programming stemmed from the fetal origins hypothesis, also known as Barker’s hypothesis, that David Barker proposed in 1995 at the University of Southampton in Southampton, England. The fetal origins hypothesis states that undernutrition in the womb during middle to late pregnancy causes improper fetal growth, which in turn, causes a predisposition to certain diseases in adulthood. In addition to nutritional impacts, researchers have studied the fetal programming effects of many factors, such as maternal anxiety or violence during pregnancy. Researchers proposing the concept of fetal programming established a new area of research into the developmental causes of disease, pointing towards the in utero environment and its critical role in healthy human development.

Published in 1971, Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women, by Arthurs L. Herbst and colleagues, was the first piece of literature connecting maternal use of the drug diethylstilbestrol (DES), also called stilbestrol, with the development of a rare and severe form of vaginal cancer in young women. Diethylstilbestrol was later classified as an endocrine disruptor, a substance that disrupts the hormonal function of the body in those exposed to it during development or later in life. After Herbst and his team established the connection between DES and the occurrence of breast cancer, cervical cancer, infertility, and reproductive abnormalities, the US federal government banned use the drug for pregnant women. The article was published in the New England Journal of Medicine.

Edward Charles Dodds researched the function and effects of natural and artificial hormones on the endocrine system in England during the twentieth century. Though he first worked with hormones such as insulin, Dodds focused on the effects of estrogen in the body and how to replicate those effects with artificial substances. In 1938, along with chemist Robert Robinson, Dodds synthesized the first synthetic estrogen called diethylstilbestrol. Despite the wide use of diethylstilbestrol to treat a variety of hormonal problems like miscarriages during pregnancy and menopause, Dodds argued against the use of synthetic substances in the human body due to their unknown effects. Just before Dodds's death, his hypotheses were confirmed when researchers showed that people exposed to diethylstilbestrol often developed cancer. Dodds was one of the first researchers to investigate the endocrine or hormone system in humans, and his research led to the creation of other synthetic hormones used in contraceptive pills and hormone replacements.

Scientists use cerebral organoids, which are artificially produced miniature organs that represent embryonic or fetal brains and have many properties similar to them, to help them study developmental disorders like microcephaly. In human embryos, cerebral tissue in the form of neuroectoderm appears within the first nine weeks of human development, and it gives rise to the brain and spinal cord. In the twenty-first century, Juergen Knoblich and Madeleine Lancaster at the Institute of Molecular Biotechnology in Vienna, Austria, grew cerebral organoids from pluripotent stem cells as a model to study developmental disorders in embryonic and fetal brains. One such disorder is microcephaly, a condition in which brain size and the number of neurons in the brain are abnormally small. Scientists use cerebral organoids, which they've grown in labs, because they provide a manipulable model for studying how neural cells migrate during development, the timing of neural development, and how genetic errors can result in developmental disorders.

William Withey Gull studied paraplegia, anorexia, and hormones as a physician in England during the nineteenth century. In addition to caring for patients, he described the role of the posterior column of the spinal cord in paraplegia, and he was among the first to describe the conditions of anorexia and of hypochondria. He also researched the effects of thyroid hormone deficiencies in women who had malfunctioning thyroid glands. Gull's research on thyroid hormone confirmed that chemicals in the body directly affect health, and he contributed to the foundation of endocrinology, the scientific field for the study of hormones.

Charles Raymond Greene studied hormones and the effects of environmental conditions such as high-altitude on physiology in the twentieth century in the United Kingdom. Green researched frostbite and altitude sickness during his mountaineering expeditions, helping to explain how extreme environmental conditions effect respiration. Greene’s research on hormones led to a collaboration with physician Katarina Dalton that culminated in the development of the theory that progesterone caused premenstrual syndrome, a theory that became the basis for later research on the condition. In his later career Greene formed the Thyroid Club of London that brought together specialists in the emerging field on endocrinology. Greene’s research on progesterone and thyroid helped researchers study how of the endocrine system functions in women’s reproductive health.

In 1953, Raymond Greene and Katharina Dalton, who were doctors in the UK, published The Premenstrual Syndrome in the British Medical Journal. In their article, Dalton and Greene established the term premenstrual syndrome (PMS). The authors defined PMS as a cluster of symptoms that include bloating, breast pain, migraine-headache, fatigue, anxiety, depression, and irritability. The article states that the symptoms begin one to two weeks before menstruation during the luteal phase of the menstrual cycle, and they disappear upon the onset of the menstrual period. Menstruation is the monthly series of changes a woman's body undergoes in preparation for the possibility of pregnancy. Dalton and Greene described how progesterone affected women during different phases of their menstrual cycles. The paper convinced many about the phenomenon of PMS, and docotors and scientists adopted Dalton's and Green's term. The paper furthered research about the role of hormones in physiology and of conditions linked to the reproductive system.

Karl Landsteiner studied blood types in Europe and in the United States in the late nineteenth and early twentieth centuries. Landsteiner won the Nobel Prize in Physiology or Medicine in 1930 for detailing immunological reactions in the ABO blood group system. The ABO blood group system divides human blood into one of four types based on the antibodies that are present on each cell. Landsteiner's work with blood types led physicians to safely perform blood transfusions and organ transplants. Additionally, Landsteiner researched the Rh blood factor, a protein marker on the surface of blood cells and that can impact pregnancy.

In 2011, Sarah McMahon and colleagues published “The Impact of Emotional and Physical Violence During Pregnancy on Maternal and Child Health at One Year Post-partum,” hereafter, “The Impact,” in the journal, Child and Youth Services Review. While existing studies had indicated negative chronic effects resulting from intimate partner violence, or IPV, such as miscarriage and premature labor, there was little research specifically analyzing the separate and joint effects of psychological and physical abuse on pregnant women and fetuses. The authors reported that both physical and emotional IPV had negative impacts on the woman and child at one-year after birth, including worse overall health and increased likelihood of depression. In “The Impact,” the researchers analyzed the effects of partner abuse during pregnancy, distinguishing between the effects of emotional abuse and physical abuse on health outcomes for a pregnant woman and her offspring.

In 2001, Kevin M. Godfrey and David J.P. Barker published the article “Fetal Programming and Adult Health” in Public Health Nutrition, where they identified the significance of maternal nutrition during pregnancy to healthy offspring development. The authors describe the effects of maternal nutrition on fetal programming of cardiovascular disease. Fetal programming is when a specific event during pregnancy has effects on the fetus long after birth. The authors argue that fetuses may adapt to varying shifts in their environment in utero, such as slowed fetal growth in response to malnutrition. While those adaptations can be helpful in utero, the authors assert they may persist into adolescence and adulthood, causing conditions such as high blood pressure or diabetes. Godfrey and Barker assert that fetal adaptations to maternal malnutrition may be implicated in the development of cardiovascular disease in adulthood, and called for future research investigating additional fetal programming variables.