Embryo Project Encyclopedia

The figure depicts three different molecular structures of estrogen found in mammals’ that differ by the arrangement of bonds and side groups. The molecular structures of the three estrogen molecules differ by the arrangement of chemical bonds and side groups attached to the core steroid structure, cholesterol, which contains three cyclohexane rings and one cyclopentane ring. Compared to the molecular structure of estriol, the molecular structure of estradiol is missing one oxygen-hydrogen or OH group, and estrone lacks the OH group, and one hydrogen molecule that results in a double bonded oxygen atom. These steroid hormones bind to specific cell receptor molecules and induce transcriptional changes in cells. The production of estriol increases during pregnancy, estradiol production increases during stages of the menstrual cycle, and estrone levels increase during menopause. The differing bonds and chemical arrangements enable scientists to determine the different concentrations of the molecules.

The sex of a reptile embryo partly results from the production of sex hormones during development, and one process to produce those hormones depends on the temperature of the embryo's environment. The production of sex hormones can result solely from genetics or from genetics in combination with the influence of environmental factors. In genotypic sex determination, also called genetic or chromosomal sex determination, an organism's genes determine which hormones are produced. Non-genetic sex determination occurs when the sex of an organism can be altered during a sensitive period of development due to external factors such as temperature, humidity, or social interactions. Temperature-dependent sex determination (TSD), where the temperature of the embryo's environment influences its sex development, is a widespread non-genetic process of sex determination among vertebrates, including reptiles. All crocodilians, most turtles, many fish, and some lizards exhibit TSD.

Isotretinoin is a molecule and a byproduct (metabolite) of vitamin A, and in greater than normal amounts in pregnant women, it can cause fetal abnormalities including cleft lips, ear and eye defects, and mental retardation. Isotretinoin is commonly called by its trade name Accutane, and it's a chemical compound derived from vitamin A, or retinoic acid. Doctors prescribe isotretinoin to treat severe acne. For pregnant women, too much vitamin A or isotretinoin can also cause greater than normal rates of stillbirths and fetal disintegrations after the ninth week of gestation. Women who use isotretinoin during the first trimester of their pregnancies, even in small amounts, risk defects to their fetuses such as external ear malformations, cleft palates, undersized jaws (micrognathia), a variety of heart defects, buildups of fluids inside the skulls that leads to brain swelling (hydrocephalus), small heads and brains (microcephaly), and mental retardation.

Eugen Steinach researched sex hormones and their effects on mammals in the late nineteenth and early twentieth centuries in Europe. He experimented on rats by removing their testicles and implanting them elsewhere in their bodies, and he found that the testes interstitial cells produce male sex hormones. He developed the Steinach Rejuvenation Procedure, which he claimed could rejuvenate men by increasing their production of sex hormones. Steinach’s work on female sex hormones and on ovarian extracts led to the development of the first standardized injectable estrogen. Steinach’s research on reproductive hormones helped researchers explain the roles of sex hormones and develop hormone drugs.

In 1996, the US Congress mandated that the US Environmental Protection Agency (EPA) create and regulate the Endocrine Disruptor Screening Program. The program tests industrial and agricultural chemicals for hormonal impacts in humans and in wildlife that may disrupt organisms' endocrine systems. The endocrine system regulates the release of small amounts of chemical substances called hormones to keep the body functioning normally. Some chemicals can impede the endocrine system's function by mimicking or blocking hormone reception, which can disrupt processes of development and reproduction and harm organisms. As of 2017, the Endocrine Disruptor Screening Program is the largest US program to identify and regulate chemicals that affect the normal production of sex hormones like estrogen and androgen, which can have long-term effects on development and reproduction.

Isidore Geoffroy Saint-Hilaire studied anatomy and congenital abnormalities in humans and other animals in nineteenth century France. Under the tutelage of his father, Etienne Geoffroy Saint-Hilaire, Isidore compiled and built on his father's studies of individuals with developmental malformations, then called monstrosities. In 1832, Isidore published Histoire generale et particuliere des anomalies de l'organisation chez l'homme et les animaux (General and Particular History of Structural Monstrosities in Man and Animals), in which he defined the term teratology as the study of birth defects and deformities. Isidore Geoffroy Saint-Hilaire established teratology as a legitimate branch of scientific study.

In the early 1920s, researchers Edgar Allen and Edward Adelbert Doisy conducted an experiment that demonstrated that ovarian follicles, which produce eggs in mammals, also contain and produce what they called the primary ovarian hormone, later renamed estrogen. In their experiment, Doisy and Allen extracted estrogen from the ovarian follicles of hogs and proved that they had isolated estrogen by using a measurement later renamed the Allen-Doisy test. Allen and Doisy’s 1923 experiment to isolate estrogen showed it was made within the ovaries and also established a method for isolating the sex hormone. That method provided a basis for future research on hormones. Later researchers showed that estrogen functions in the menstrual cycles of primates by signaling for the tissue lining the uterus (endometrium) to thicken in preparation for possible implantation of a fertilized egg.

The article Experimental Studies on Congenital Malformations was published in the Journal of Chronic Diseases in 1959. The author, James G. Wilson, studied embryos and birth defects at the University of Florida Medical School in Gainesville, Florida. In his article, Wilson reviewed experiments on birds and mammals from the previous forty years to provide general principles and guidelines in the study of birth defects and teratogens, which are things that cause birth defects. Those principles included what species are convenient for conducting teratological research, what principles act in human embryological and fetal development, and what agents impact those processes. Wilson's article was one of the first attempts in the twentieth century to synthesize basic research conducted in the field of teratology. The article helped to establish teratology as a field in medicine during the twentieth century.

Norman Haire was a physician who advocated for eugenics, which is the betterment of human population by promoting positive traits, and birth control rights in the twentieth century in both Australia and the UK. In the UK, Haire joined the Malthusian League, a contraception advocacy organization, and helped the League open the first physician-supervised birth control clinic, called Walworth Women’s Welfare Centre in London, England. Throughout his life, Haire worked closely with other well-known contraception and women’s rights advocates in the early 1900s including Margaret Sanger, Marie Stopes, and Havelock Ellis. Haire was also known for his work on sexual rejuvenation, an early twentieth century theory that the male sexual appetite could be restored through vasectomies and hormonal injections. Haire advocated for birth control rights through his practice, conference lectures, radio debates, and published work. His activism in the fields of eugenics, contraception, and sexual reform promoted the emergence of more liberal attitudes towards sex and controlled reproduction and in the twentieth century.

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.