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.

Human pluripotent stem cells are valued for their potential to form numerous specialized cells and for their longevity. In the US, where a portion of the population is opposed to destruction of human embryos to obtain stem cells, what avenues are open to scientists for obtaining pluripotent cells that do not offend the moral sensibilities of a significant number of citizens? It is this question that the official position paper, or white paper, "Alternative Sources of Human Pluripotent Stem Cells," published in May 2005 by the President's Council on Bioethics under the chairmanship of Leon Kass, seeks to answer. Three experts external to the council, Andrew Fire from the Stanford University School of Medicine, Markus Grompe of the Oregon Health and Science University, and Janet Rossant from the Samuel Lunenfeld Research Institute in Toronto, also reviewed the white paper prior to publication.

Matthew Kaufman was a professor of anatomy at the University of Edinburgh, in Edinburgh, UK, who specialized in mouse anatomy, development, and embryology during the late twentieth century. According to the The Herald, he was the first, alongside his colleague Martin Evans, to isolate and culture embryonic stem cells. Researchers initially called those cells Evans-Kaufman cells. In 1992, Kaufman published The Atlas of Mouse Development, a book that included photographs of mice development and mice organs over time. Kaufman also wrote books about UK medical history, phrenology, or the study of craniums as an indicator of character or mental ability, and medical teaching in the eighteenth and nineteenth centuries. Kaufman’s anatomical records and experiments in mouse development contributed to genetic engineering, embryology, and anatomy.

In the twentieth and early twenty-first centuries, Gail Roberta Martin specialized in biochemistry and embryology, more specifically cellular communication and the development of organs. In 1981, she named any cell taken from inside a human embryo at the blastocyst stage an “embryonic stem cell”. During development, an embryo goes through the blastocyst stage just before it implants in the uterus. Embryonic stem cells are useful for experiments because they are self-renewing and able to develop into almost any cell type in the body. Martin later identified a key chemical component in limb development and continues to study embryogenesis, or the growth of embryos over time. Martin’s work on embryonic stem cells has allowed scientists to further research and treat human diseases, and her study of how organs form has helped scientists learn about the healthy growth of embryos.

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.