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.

Thomas Joseph King Jr. was a developmental biologist who, with fellow scientist Robert Briggs, pioneered a method of transplanting nuclei from blastula cells into fresh egg cells lacking nuclei. This method, dubbed nuclear transplantation, facilitated King's studies on cancer cell development. King's work was instrumental for the development of cloning of fish, insects, and mammals.

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.

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.

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.

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.

In the early twentieth century US, Jean Paul Pratt and Edgar Allen conducted clinical experiments on women who had abnormal menstrual cycles. During the clinical tests, researchers injected the hormone estrogen into their patients to alleviate their menstrual ailments, which ranged from irregular cycles to natural menopause. The hormone estrogen plays a prominent role in the menstrual cycle by signaling the tissue lining the uterus (endometrium) to thicken in preparation for possible pregnancy. In their clinical tests, Pratt and Allen showed that injecting estrogen into female human subjects restored their normal menstrual cycle, removed symptoms such as hot flashes, and caused uterine tissue to grow. The clinical tests conducted by Pratt and Allen provided experimental evidence and justification for the injection of isolated estrogen in women to alleviate, for a short amount of time, different menstrual problems, and it contributed to later hormone therapy research.

Sindell v. Abbott Laboratories was a 1980 California case that established the doctrine of market share liability for personal injury cases. For such liability, when a drug causes personal injury and the manufacturer of the drug cannot be identified, each producer is responsible for paying the settlement in proportion to the percentage of the market they supplied. Judith Sindell and Maureen Rogers brought the case against the producers of diethylstilbestrol (DES), which their mothers had taken during pregnancy to prevent miscarriage and other complications. Sindell and Rogers alleged that their mothers' ingestions of DES during pregnancy later caused Sindell and Rogers to develop cancers at the onset of puberty, but they could not identify the specific manufacturer of the drug. The market share liability ruling in Sindell allowed millions of DES-affected individuals to seek restitution for reproductive cancers caused by prenatal exposure to DES.

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.

In 1894, William Stewart Halsted published The Results of Operations for the Cure of Cancer of the Breast Performed at the Johns Hopkins Hospital from June, 1889, to January, 1894, in the medical journal Annals of Surgery. In the article, Halsted describes the results from fifty of his operations on women with breast cancer, performed at Johns Hopkins Hospital in Baltimore, Maryland. Those operations involved a surgical procedure Halsted called radical mastectomy, which consists in removing all of the patient’s breast tissue, chest muscle, and underarm lymph nodes. Halsted’s surgery effectively cured breast cancer in a time period when no other effective treatment options were available. The radical mastectomy remained the standard of care from the 1890s to the 1970s as a means of treating a type of reproductive cancer common to women.