Embryo Project Encyclopedia

Between February 1969 and August 1970 Edward Kollar and Grace Baird, from the University of Chicago in Chicago, Illinois, published three papers that established the role of the mesenchyme in tooth induction. Drawing upon a history of using tissue interactions to understand differentiation, Kollar and Baird designed their experiments to understand how differentiated structures become specified. Their work overturned a widely accepted model that epithelium controls the identity of the structure, a phenomenon called structural specificity. Interactions between epithelium and mesenchyme control the development and differentiation of many parts during embryonic development, including structures like the gastrointestinal tract and hair. Thus, the realization that mesenchyme drives induction and differentiation during epithelio-mesenchymal interactions had far-reaching effects.

This project focuses on the history of how teratogens, or agents which have the potential to cause birth defects, have been understood and tested for teratogenic potential in the US over the twentieth century. Prior to this time, teratogen studies were primarily concerned with cataloguing defects rather than exploring possible causes. At the turn of the twentieth century, experimental teratogen studies with the aim of elucidating mechanisms commenced. However, these early studies did not aim to discover human pregnancy outcomes and ways to prevent them, but simply focused on the results of exposing pregnant mammals to various physical and chemical insults.

Theodora Colborn studied how chemicals affect organisms as they develop and reproduce during the twentieth and twenty first centuries in the US. By the 1940s, researchers had reported that chemicals from agricultural and industrial processes affected how wild organisms developed, but in 1991, Colborn organized the Wingspread Conference in Racine, Wisconsin, at which a group of scientists classed these chemicals as environmentally harmful substances. Colborn and her colleagues called those chemicals endocrine disruptors, as they mimic or block the body's endocrine system. After scientists identified these chimicals and showed that they harm humans and wildlife, US Congress passed several acts to regulate these chemicals and to protect both wildlife and humans from their harmful effects.

Mesoderm is one of the three germ layers, groups of cells that interact early during the embryonic life of animals and from which organs and tissues form. As organs form, a process called organogenesis, mesoderm interacts with endoderm and ectoderm to give rise to the digestive tract, the heart and skeletal muscles, red blood cells, and the tubules of the kidneys, as well as a type of connective tissue called mesenchyme. All animals that have only one plane of symmetry through the body, called bilateral symmetry, form three germ layers. Animals that have only two germ layers develop open digestive cavities. In contrast, the evolutionary development of the mesoderm allowed in animals the formation of internal organs such as stomachs and intestines (viscera).

Diethylstilbestrol (DES) is an artificially created hormone first synthesized in the late 1930s. Doctors widely prescribed DES first to pregnant women to prevent miscarriages, and later as an emergency contraceptive pill and to treat breast cancer. However, in 1971, physicians showed a link between DES and vaginal cancer during puberty in the children of women who had taken DES while pregnant. Consequently, the US Food and Drug Administration (FDA) banned its use during pregnancy. In the late 2000s, several studies showed that the grandchildren of women who had consumed DES also suffered medical issues. By the early decades of the twenty-first century, roughly ten million people in the US had been exposed to DES, and three generations of individuals had suffered medical issues due to DES exposure. Researchers class DES as an endocrine disruptor, which affects the form and function of the hormone (endocrine) system.

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.

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

Diana W. Bianchi studied the medical treatment of premature and newborn infants in the US during the twentieth and twenty-first centuries. Bianchi helped develop non-invasive prenatal genetic tests that use cell-free fetal DNA found within maternal blood to diagnose genetic abnormalities of the fetus during pregnancy. The test provides a means to test fetuses for chromosomal and genetic abnormalities.

Carl Richard Moore was a professor and researcher at the University of Chicago in Chicago, Illinois who studied sex hormones in animals from 1916 until his death in 1955. Moore focused on the role of hormones on sex differentiation in offspring, the optimal conditions for sperm production, and the effects of vasectomy or testicular implants on male sex hormone production. Moore's experiments to create hermaphrodites in the laboratory contributed to the theory of a feedback loop between the pituitary and fetal gonadal hormones to control sex differentiation. Moore showed that the scrotal sac controls the temperature for the testes, which is necessary for sperm production. He also helped distinguish the hormones testosterone, and androsterone from testicular extracts.

Vitamin A (retinol) is an essential vitamin in the daily functioning of human beings that helps regulate cellular differentiation of epithelial tissue. Studies have shown that an excess of vitamin A can affect embryonic development and result in teratogenesis, or the production of birth defects in a developing embryo. Excess intake of vitamin A and retinoids by pregnant women often results malformations to fetuses' skulls, faces, limbs, eyes, central nervous system. Additionally, doctors often use derivatives of vitamin A, known as retinoids, as medicine to treat a number of skin conditions and carcinomas, the most common form of human cancers.