Embryo Project Encyclopedia

In December 2011, the Stillbirth Collaborative Research Network, or SCRN, published the article “Causes of Death Among Stillbirths” in The Journal of the American Medical Association. The authors of the article investigate the causes of stillbirth and possible reasons for the racial, ethnic, and geographic disparities in stillbirth rates. According to the Centers for Disease Control and Prevention, or CDC, stillbirth is the death of a fetus at twenty or more weeks during pregnancy. “Causes of Death Among Stillbirths” explores the common causes of stillbirth in different racial and ethnic groups, and provides a framework for future research into medical interventions to help reduce racial and ethnic stillbirth disparity.

In April 1994, Elizabeth Raymond, Sven Cnattingius, and John Kiely published “Effects of Maternal Age, Parity, and Smoking on the Risk of Stillbirth” in the British Journal of Obstetrics and Gynecology, now known as BJOG: An International Journal of Obstetrics and Gynecology. The article examines how advanced maternal age, defined as delivery at thirty-five years old or older, cigarette smoking, and nulliparity, or the state of never having given birth, can negatively impact pregnancy. At the time of publication, according to Raymond and colleagues, stillbirths comprised over half of all perinatal, or close to birth, deaths and more than one-third of total fetal and infant deaths in Europe and North America. In the article, Raymond and her coauthors demonstrate how certain risk factors may increase the risk of stillbirth at different stages of pregnancy, which helped set a foundation for future research in interventions to prevent stillbirth.

In the early 2000s, Manjong Han, Xiaodang Yang, Jennifer Farrington, and Ken Muneoka investigated how genes and proteins in fetal mice (Mus musculus) influenced those fetal mice to regenerate severed toes at Tulane University in New Orleans, Louisiana. The group used hind limbs from mice to show how the gene Msx1 (Homeobox 7) functions in regenerating amputated digits. The researchers showed that in the process of regenerating digit tips, Msx1 genes make products that regulate or influence other genes, such as the Bone Morphogenetic Protein 4 gene (BMP4 gene), to produce proteins, such as the BMP4 proteins. The researchers also showed that BMP4 proteins, which are produced from the BMP4 gene, function in tissues during the process of limb development. Furthermore, while Msx1 genes regulate other genes during the process of regeneration, they don't produce proteins otherwise needed to organize cells in the regeneration of digit tissues. The group published their results in 2003 as Digit Regeneration Is Regulated by Msx1 and BMP4 in Fetal Mice.

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.

Edgar Allen identified and outlined the role of female sex hormones and discovered estrogen in the early 1900s in the US. In 1923, Allen, through his research with mice, isolated the primary ovarian hormone, later renamed estrogen, from ovarian follicles and tested its effect through injections in the uterine tissues of mice. Allen’s work on estrogen, enabled researchers to further study hormones and the endocrine system.

Karl Oskar Illmensee studied the cloning and reproduction of fruit flies, mice, and humans in the US and Europe during the twentieth and twenty-first centuries. Illmensee used nuclear transfer techniques (cloning) to create early mouse embryos from adult mouse cells, a technique biologists used in later decades to help explain how embryonic cells function during development. In the early 1980s, Illmensee faced accusations of fraud when others were unable to replicate the results of his experiments with cloned mouse embryos. Illmensee also worked with human embryos, investigating how embryos split to form identical twins.

In 1953, Raymond Greene and Katharina Dalton, who were doctors in the UK, published The Premenstrual Syndrome in the British Medical Journal. In their article, Dalton and Greene established the term premenstrual syndrome (PMS). The authors defined PMS as a cluster of symptoms that include bloating, breast pain, migraine-headache, fatigue, anxiety, depression, and irritability. The article states that the symptoms begin one to two weeks before menstruation during the luteal phase of the menstrual cycle, and they disappear upon the onset of the menstrual period. Menstruation is the monthly series of changes a woman's body undergoes in preparation for the possibility of pregnancy. Dalton and Greene described how progesterone affected women during different phases of their menstrual cycles. The paper convinced many about the phenomenon of PMS, and docotors and scientists adopted Dalton's and Green's term. The paper furthered research about the role of hormones in physiology and of conditions linked to the reproductive system.

Estrogen is the primary sex hormone in women and it functions during the reproductive menstrual cycle. Women have three major types of estrogen: estrone, estradiol, and estriol, which bind to and activate receptors within the body. Researchers discovered the three types of estrogen over a period of seven years, contributing to more detailed descriptions of the menstrual cycle. Each type of estrogen molecule contains a slightly different arrangement or number of atoms that in turn causes some of the estrogens to be more active than others. The different types of estrogen peak and wane throughout women's reproductive cycles, from normal menstruation to pregnancy to the cessation of menstruation (menopause). As scientists better explained the effects of estrogens, they used that information to develop oral contraceptives to control pregnancy, to map the menstrual cycle, and to create hormone therapies to regulate abnormal levels of estrogen.

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.

Roy John Britten studied DNA sequences in the US in the second
half of the twentieth century, and he helped discover repetitive
elements in DNA sequences. Additionally, Britten helped propose
models and concepts of gene regulatory networks. Britten studied the
organization of repetitive elements and, analyzing data from the
Human Genome Project, he found that the repetitive elements in DNA
segments do not code for proteins, enzymes, or cellular parts.
Britten hypothesized that repetitive elements helped cause cells to
differentiate into more specific cell kinds among different
organisms.