Embryo Project Encyclopedia

Mechanism of Notch Signaling: The image depicts a type of cell signaling, in which two animal cells interact and transmit a molecular signal from one to the other. The process results in the production of proteins, which influence the cells as they differentiate, move, and contribute to embryological development. In the membrane of the signaling cell, there is a ligand (represented by a green oval). The ligand functions to activate a change in a receptor molecule. In the receiving cell, there are receptors; in this case, Notch proteins (represented by orange forks). The Notch proteins are embedded in the receiving cell membrane, and they have at least two parts: an intracellular domain (inside the cell) and the receptor (outside the cell). Once the ligand and receptor bind to each other, a protease (represented by the dark red triangle) can sever the intracellular domain from the rest of the Notch receptor. Inside the nucleus of the receiving cell (represented by the gray area) are the cellês DNA (represented by the multi-colored helices) and its transcription factors (blue rectangles). Transcription factors are proteins that bind to DNA to regulate transcription, the first step in gene expression, which eventually yields proteins or other products. Initially, repressor proteins (represented by a red irregular hexagon) prevent transcription factors from allowing transcription. When the severed Notch receptor intracellular domain reaches the nucleus, it displaces the repressor. The transcription factor can then signal for transcription to occur. 1) There is a Notch receptor protein in the membrane of a receiving cell, and a ligand for this receptor (for example, Delta) in the membrane of the signaling cell. When the ligand binds to the receptor, the intracellular domain of the receptor changes shape. 2) Inside the receiving cell, there are proteases. Once the intracellular domain of the receptor changes shape, the protease can bind to it and shear the intracellular domain away from the rest of the receptor molecule. 3) The severed intracellular domain is shuttled to the receiving cell nucleus. Here, the intracellular domain displaces a repressor protein. This allows a transcription factor to initiate DNA transcription. During transcription, DNA is used as a template to create RNA. Following transcription, the process of translation occurs, which uses RNA as a template to create proteins. These proteins influence the behavior, fate, and differentiation of cells, which contribute to normal embryonic development

Orchiopexy, also known as orchidopexy, is a surgical technique that can correct cryptorchidism and was successfully performed for one of the first times in 1877 in Scotland. Cryptorchidism, a condition where one or both of the testicles fail to descend before birth, is one of the most common male genital birth defects, affecting approximately 2 to 8 percent of full-term male infants, and around 33 percent of premature infants. Typically in the womb, male testes form within the abdomen, then descend into the scrotal area between twenty-five to thirty-five weeks’ gestation. If one or both testicles fail to descend before birth, physicians use orchiopexy to surgically relocate the undescended testes to their normal position in the scrotum. According to many researchers, most cases of cryptorchidism do not resolve on their own, and therefore, orchiopexy surgery is often necessary. Orchiopexy, when performed before puberty, can decrease the risk of testicular cancer and infertility associated with cryptorchidism.

First manufactured in 1988 by Serono laboratories, recombinant gonadotropins are synthetic hormones that can stimulate egg production in women for use in fertility treatments. Recombinant gonadotropins are artificially created using recombinant DNA technology, a technology that joins together DNA from different organisms. In vertebrates, naturally-occurring gonadotropins regulate the growth and function of the gonads, known as testes in males and ovaries in females. Medical professionals can derive female gonadotropins from the urine of pregnant and post-menopausal women, often using it to facilitate in vitro fertilization, or IVF. With the rapid development of assisted reproductive technologies like IVF, demand for human-derived gonadotropins rose to a global yearly demand of 120 million liters of urine by the beginning of the twenty-first century, which resulted in a demand that could not be met by traditional technologies at that time. Therefore, researchers created recombinant gonadotropins to establish a safer and more consistent method of human gonadotropin collection that met the high demand for its use in fertility treatments.

'On the Permanent Life of Tissues outside of the Organism' reports Alexis Carrel's 1912 experiments on the maintenance of tissue in culture media. At the time, Carrel was a French surgeon and biologist working at the Rockefeller Institute in New York City. In his paper, Carrel reported that he had successfully maintained tissue cultures, which derived from connective tissues of developing chicks and other tissue sources, by serially culturing them. Among all the tissue cultures Carrel reported, one was maintained for more than two months, whereas previous efforts had only been able to keep tissues in vitro for three to fifteen days. Carrel’s experiments contributed to the development of long-term tissue culture techniques, which were useful in the study of embryology and eventually became instrumental in stem cell research. Despite later evidence to the contrary, Carrel believed that as long as the tissue culture method was accurately applied, tissues kept outside of the organisms should be able to divide indefinitely and have permanent life.

In 2007, Ishola Agbaje, Deirdre Rogers, Carmel McVicar, Neil McClure, Albert Atkinson, Con Mallidis, and Sheena Lewis published “Insulin Dependent Diabetes Mellitus: Implications for Male Reproductive Function,” hereby “Diabetes Mellitus: Implications,” in the journal Human Reproduction. In their article, the authors explore the effects of elevated blood sugar in the form of diabetes mellitus on the quality of male sperm. When investigating possible fertility issues, fertility specialists often study semen, the male reproductive fluid that contains sperm cells to detect changes in sperm count, movement, and structure. In “Diabetes Mellitus: Implications,” the authors use both conventional semen analysis and technical molecular methods to assess the quality of sperm from diabetic and non-diabetic men. The authors found that men with diabetes had higher levels of DNA damage within their sperm and highlighted a need for additional research on the link between diabetes and male reproductive health.

In the twentieth century, researchers developed the oral glucose tolerance test, or OGTT, as a method to diagnose different types of diabetes, a medical condition that causes blood sugar levels to become abnormally high. During the test, a healthcare provider measures a person’s blood sugar levels before and after the person consumes a predetermined amount of glucose solution. While not exclusively used for pregnant women, an OGTT may test for gestational diabetes which, according to the International Diabetes Federation, affected one in six pregnancies worldwide in 2019. Generally, the results from an OGTT can inform a patient and her physician how her body is responding to glucose during pregnancy, and high levels may increase her risk of developing adverse pregnancy outcomes such as heavy bleeding during delivery and a high blood pressure condition known as preeclampsia. An OGTT can help to accurately diagnose, treat, and monitor gestational diabetes in pregnant women, which can reduce health and pregnancy complications for the woman and the fetus.

Christiane Nusslein-Volhard studied how genes control embryonic development in flies and in fish in Europe during the twentieth and twenty-first centuries. In the 1970s, Nusslein-Volhard focused her career on studying the genetic control of development in the fruit fly Drosophila melanogaster. In 1988, Nusslein-Volhard identified the first described morphogen, a protein coded by the gene bicoid in flies. In 1995, along with Eric F. Wieschaus and Edward B. Lewis, she received the Nobel Prize in Physiology or Medicine for the discovery of genes that establish the body plan and segmentation in Drosophila. Nusslein-Volhard also investigated the genetic control of embryonic development to zebrafish, further generalizing her findings and helping establishing zebrafish as a model organism for studies of vertebrate development.

Transvaginal ultrasound-guided oocyte retrieval, also known as egg retrieval, is a surgical technique used by medical professionals to extract mature eggs directly from the women’s ovaries under the guidance of ultrasound imaging. In 1982, physicians Suzan Lenz and Jorgen Lauritsen at the University of Copenhagen in Copenhagen, Denmark, proposed the technology to improve the egg collection aspect of in vitro fertilization, or IVF. During IVF, a healthcare practitioner must remove mature eggs from a woman’s ovaries to fertilize them with sperm outside of the body. Transvaginal ultrasound-guided egg retrieval is a surgery that can be completed in a medical office setting in twenty minutes. Transvaginal ultrasound-guided egg retrieval increased mature egg collection and rates of successful fertilization, becoming the new standard for egg collection in IVF.

Researchers Geoffrey Sher and Jeffrey Fisch gave Viagra, also known as sildenafil, to women undergoing fertility treatment to test whether the medication could improve fertility and pregnancy rates. The researchers proposed that Viagra, typically indicated to treat erectile dysfunction in men, would help women with a history of failed past fertility treatments by thickening their endometrial lining, which is the layer of tissue in the uterus where an embryo implants during pregnancy. Sher and Fisch gave the women Viagra during in vitro fertilization, or IVF, an assisted reproductive technology. They summarized their findings in the article “Effect of Vaginal Sildenafil on the Outcome of In Vitro Fertilization (IVF) After Multiple IVF Failures Attributed to Poor Endometrial Development,” published in Fertility and Sterility in 2002. Although they noted additional research was needed, Sher and Fisch concluded that the prescribed combination treatment of Viagra and IVF resulted in an increased thickening of the endometrium lining which enabled the embryo to implant and result in a pregnancy.

In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene expression. Britten worked at the Carnegie Institute of Washington in Washington, D.C., while Davidson worked at the California Institute of Technology in Pasadena, California. Their paper was an early theoretical and mechanistic description of gene regulation in higher organisms.