Embryo Project Encyclopedia Articles

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.

Josef Warkany studied the environmental causes of birth defects in the United States in the twentieth century. Warkany was one of the first researchers to show that factors in the environment could cause birth defects, and he helped to develop guidelines for the field of teratology, the study of birth defects. Prior to Warkany’s work, scientists struggled to explain if or how environmental agents could cause birth defects. Warkany demonstrated that a deficiency or excess of vitamin A in maternal nutrition could cause birth defects. He also established that mercury in teething powders increased infant mortality rates. Warkany showed how substances outside the human body could adversely affect conception, growth, and development of the human fetus in utero.

In its 1993 decision Daubert v. Merrell Dow Pharmaceuticals, Inc., the US Supreme Court established the Daubert Standard for evaluating the admissibility of scientific knowledge as evidence in US federal courts. When it began in trial court, the case addressed whether or not Bendectin, an anti-nausea medication taken during pregnancy, caused birth defects. However, after the trial court dismissed the case for lack of admissible evidence, Daubert v. Merrell Dow Pharmaceuticals, Inc. advanced through appeals courts to the US Supreme Court, where the Justices defined the criteria by which scientific knowledge, which for them included a least theories based on evidence, expert testimony from scientists, and scientific techniques, could be introduced and used in court cases as evidence. The Daubert Standard states that the judge of a case is responsible for determining what claims are admissible as scientific knowledge and as evidence in the case. The admissibility should be determined by the falsifiability of the claims, by whether or not they had passed peer reviewed, by the general scientific acceptance of the claims, and for techniques, by their error rates of the techniques. Daubert v. Merrell Dow Pharmaceuticals, Inc. set a landmark precedent in the US judicial system and influenced most subsequent legal cases that appealed to science to establish facts in trials.

Fortunio Liceti studied natural philosophy and medicine in Italy during the first half of the seventeenth century. Liceti wrote greater than seventy works on a wide range of topics, including the human soul, reproduction, and birth defects observed in animals and human infants. In the seventeenth century, people commonly addressed birth defects using superstition and considered them as signs of evil, possibly caused by spiritual or supernatural entities. Liceti described infants with birth defects as prodigies and monsters to be admired and studied rather than feared. Liceti’s works established monsters as a possible subject of scientific inquiry and served as models for the future study of birth defects, a field later called teratology. Liceti was one of the first scholars to attempt to systematically categorize birth defects based on their causes, including multiple causes unrelated to the supernatural.

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.

Truman William Brophy developed a cleft palate surgical repair, later called the Brophy Operation, in the late nineteenth century US. The procedure improved facial aesthetics and speech in cleft palate patients. A cleft palate occurs during development when the palatal bones in the roof of the mouth don't completely fuse, leaving an opening, or cleft, in the upper lip and mouth. Brophy's cleft repair used compression inside and outside of the mouth to push the palatal bones into normal alignment shortly after birth. Brophy advocated surgery on newborns with cleft palates as soon as possible after birth, which met with opposition in the late nineteenth and early twentieth centuries when medical professionals did not operate on infants for non-life threatening conditions. However, Brophy's successful operations convinced many doctors to adopt his technique.

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.