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Embryology Teaching: an Often-Neglected Part of the Medical

Embryology Teaching: an Often-Neglected Part of the Medical

Embryology Teaching Rev Arg de Anat Clin; 2017, 9 (2): 47-51 ______

Editorial

EMBRYOLOGY TEACHING: AN OFTEN-NEGLECTED PART OF THE MEDICAL CURRICULUM Ivan Varga Institute of and Embryology, Faculty of , Comenius University in Bratislava, Slovak Republic

emergence of anatomical variations, anomalies. The knowledge of embryology is also beneficial for medical students in the preparation for the exam in Gynecology and (infertility disorders and assisted reproduction techniques, structure and function of the , the factors affecting the development of the ), as well as in Pediatrics and Surgery (problems of congenital developmental defects and anatomical variations).

Historical Introduction Intrauterine development has fascinated mankind since time immemorial. In the beginning, there were mainly religious reasons that forced to think about when a new human life starts. An philosopher (384-322 B.C.) predicted that a developing individual does not have its own soul in the early stages of development ( inanimatus, Embryology is a science of the origin and unsouled fetus). At the beginning of devel- development of living organisms. The study of opment, it has only a vegetative and later animal human embryology has theoretical (as a pre- soul, and it is, therefore, similar to plants and clinical course during medical study), but also lower animals. He was based on his theory of important clinical significance. Embryology is a in which single organs of an individual fascinating field of science which can guide develop from a simpler to more complex form. students of medicine or natural sciences in a With some modifications, the concept of delayed miraculous way through the laws of human - at 40 or 90 days after fertilization - development from fertilization to birth. Owing to was adopted for example by Saint Thomas embryology, we get to know ourselves because Aquinas and remained valid throughout centuries we all went through this period of development (Obladen, 2017). Basic processes that today we (although we do not remember it). This issue will refer to as fertilization and subsequent early again capture our attention or has already done it development were previously ambiguous (it was in time when we are about to become parents or a period without a quality light microscope). On grandparents, and we will be interested in the the one hand, there was Aristotelian theory of development of our children or grandchildren. epigenesis, i.e. the theory of gradual evolution of Regarding medical studies, embryology facilitates individual organs. On the other hand, there was the study of as it can also explain the formed the theory of under

47 Direc. Nac. de Derecho de Autor Reg. Nº: 5291682 www.anatclinar.com.ar Embryology Teaching Rev Arg de Anat Clin; 2017, 9 (2): 47-51 ______which the already finished miniature organism 1. Embryology as Part of Biological Sciences was hiding inside the germ cells. There were two Embryology provides evidence for the competing models of preformationism: ovism and development of man as a result of the evolution spermism (animalculism). According to ovists, a of the animal kingdom. woman's oocyte is the essence of a new of man is a condensed and abbreviated repetition individual, whereas the only serves to start of the continued gradual evolutionary devel- the developmental process. The father of ovist opment of the whole subphylum of , preformationism is an English physiologist even the entire animal kingdom. Vertebrates William Harvey (1578-1657) who asserted "omne resemble each other in the early stages of vivum ex ovo" (all life begins from an ). In embryonic development and differences appear contrast, there were animalculists, e.g. the along with their gradual embryonic development. inventor of the light microscope Dutchman This rule was first noticed by , and Antony van Leeuwenhoek. Leeuwenhoek (1632- he named it as the recapitulation theory, or 1723) together with his colleague Ham first biogenetic law ( recapitulates observed by light sperm and believed phylogeny) (Olsson et al., 2017). Even in the they saw in its a preformed human being development of man, there could find many (so-called homunculus). Primitive preformed examples that confirm Haeckel's hypothesis. We opinions were revised in the 18th century by a cite the following examples: German-Russian physiologist and one of the  the presence of branchial (pharyngeal) founders of embryology Caspar Friedrich Wolff arches on the cranial end of the embryo (1733-1794). Wolff in his dissertation "Theoria during the 4th and 5th week of development Generationis" revived and supported Aristotle's that resemble gills of aquatic animals theory of epigenesis. He assumed that the  the gradual emergence of all stages of gradual development of an individual is controlled (, meso- by a kind of “vis essentialis", i.e. life or formative nephros, and metanephros) also in humans, force (Van Speybroeck et al., 2002). while some were characteristic only for fish or Embryology as a modern science began to amphibian develop after the discovery of a light microscope.  the development of the as the Thanks to the development of microscopic common end portion of the digestive and techniques, a German-Latvian Heinz C. urogenital system, typical of the class of Pander (1794-1865) managed to describe the animals from fishes to birds three germ layers in the chick embryo. The  the morphology of the developing presence of germ layers also in other animal also reminds the heart of particular classes of species was confirmed by an Estonian animals (the embryonic heart tube with its (1792-1876). In 1842, Von inflow and outflow portion is similar to the Baer formulated the basic laws of embryo- heart of fishes, etc.) genesis, including for example a postulate that  the formation of reminds the general structural relations are likewise segmented body structure (segmentation) of formed before the most specific appear (e.g. the some and vertebrates skin has in embryogenesis the equal basis in all  the hematopoietic function of the vertebrates, and only later there are formed and spleen during the intrauterine devel- scales, feathers, or hair).Von Baer laws were the opment reminds the function of these organs basis also for publishing the work of an English in those animals (fish and amphibian larvae) biologist (1809-1882), entitled that have no marrow yet "" (1859). Darwin's theory of evolution influenced many scientists, At this point, I would like to remind the words of a such as a German biologist Ernst Haeckel (1834- giant of Czech embryology, Professor Jaroslav 1919). His work "Anthropogenie" (1874) is often Slipka, MD, DSc. (1926-2013): "Every tissue or considered as one of the first textbooks of has their own history. History has two embryology. - ontogenesis and phylogenesis. Both are This historical overview also shows that equally important." embryology has always been at the center of concerns of physicians and natural scientists. But 2. Relevance of Embryology to the Study of what is the current status of embryology at Anatomy medical schools? There are several reasons why Another important function of embryology is to embryology is an appropriate component of the provide a logical basis for understanding the standard medical curriculum. These reasons are overall organization of the . equally important, so their order is more or less Embryology describes the development of the random. body organs of the adult and explains the

48 Direc. Nac. de Derecho de Autor Reg. Nº: 5291682 www.anatclinar.com.ar Embryology Teaching Rev Arg de Anat Clin; 2017, 9 (2): 47-51 ______emergence of possible variations in their number, understanding of the normal development of man changes to final position or topographic particul- before birth. Improving the methods of prenatal arities of human anatomy (variant anatomy). The diagnosis (amniocentesis, ultrasound, fetoscopy, variant anatomy is a specific large subfield of biochemical screening or analysis of free fetal gross anatomy. Anomalies of the human body DNA from maternal blood) allows early detection which are not considered as serious defects of of many birth defects, identify their causes and by the development that means they do not impair novel operating procedures, it is sometimes the function are considered as variants (Kachlik possible also to remove the consequences (Rink et al., 2016). Especially in the areas of surgery and Norton, 2016; Van den Veyver, 2016). To and radiology, it is important to think about the date, there has been a range of developmental possible anatomical variations, and therefore it is anomalies that can be corrected during the fetal important to understand the laws of embryology period in the (so-called fetal surgery). In for each clinical discipline. fact, the wounds after such surgery heal much better in utero; however, the development of fetal 3. Relevance of Embryology to Prenatal surgery is still limited by financial, technical, and Diagnosis professional demands of the performance and by Modern embryology deals not only with a high risk for subsequent preterm delivery morphogenesis - the development of organs but (because the human amnion does not heal, also with various developmental disorders that leading to a significant incidence of premature result in birth defects (congenital anomalies). rupture of the membranes) (Kitagawa and First and foremost, an obstetrician and Pringle, 2017). In the future, there might also be pediatrician should be thoroughly familiar with the possible the correction of the identified human development before birth. Every doctor chromosomal fetal anomalies (), or encounters congenital anomalies in their practice. there will be more extended also a replacement A precondition for recognizing birth defects, therapy with the administration of products of understanding their formation during devel- defective genes (e.g. enzyme replacement opment and often a successful treatment is the therapy).

1. Susceptibility to teratogenesis depends on the genotype of the conceptus and a manner in which this interacts with adverse environmental factors. 2. Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence. 3. Teratogenic agents act in specific ways (mechanisms) on developing cells and tissues to initiate sequences of abnormal developmental events (pathogenesis). 4. The final manifestations of abnormal development are death, malformation, growth retardation, and functional disorder. 5. The access of adverse environmental influences to developing tissues depends on the of the influences (agent). 6. Manifestations of deviant development increase in frequency and degree as dosage increases from the no-effect to the totally lethal level.

Table 1. Wilson's Six Principles of Reviewed by Friedman (2010)

4. Embryology and Understanding of usually sufficient. The principles of teratology Congenital Anomalies were published in 1959 by James G. Wilson A scientific discipline teratology (from Greek (1915-1987). He expanded the original five teratos - monster, malformation) deals with the principles in 1977 to six (Table 1). Teratology causes of congenital defects. It is important to uses the methods of experimental embryology know harmful teratogenic factors and their effects (based on animal models), develops test on the developing organism at certain periods to methods for embryo-toxicity on tissue cultures produce healthy offspring. On the other hand, and aids to discover the causes of serious nowadays, there is already evidence of the developmental malformations. Over the past 50 embryo-protective effect of certain vitamins (such years, the Teratology Society (USA) has also as folic acid) whose intake in natural form is not developed the scientific basis to prevent birth

49 Direc. Nac. de Derecho de Autor Reg. Nº: 5291682 www.anatclinar.com.ar Embryology Teaching Rev Arg de Anat Clin; 2017, 9 (2): 47-51 ______defects caused by rubella and alcoholism, as well understand the concomitant occurrence of large as other prenatal exposures (Shepard et al., intestine motility disorders (e.g. Hirschsprung 2010). disease) with congenital defects of the urinary system and the heart (Slavikova et al., 2015). 5. Clinical Embryology and Reproductive Medicine Quo Vadis Embryology Teaching? With the development of methods of reproductive This overview also shows that embryology is not medicine, there specifically developed also a new a closed static field with a set of stable and laboratory discipline, clinical embryology. unchangeable knowledge. Embryology is growing Assisted reproduction is a medical discipline that by the development of biological sciences, like all deals with oocytes, sperm and outside branches of medicine, and must, therefore, the body (in vitro) aimed at a woman to get respond to ever increasing range of knowledge pregnant (infertility treatment). Currently, the field also in the curriculum. Today, modern embryol- of reproductive medicine includes also the issues ogy examines the development of man from the of freezing of and embryos (cryo- macroscopic description up to gene expression. preservation), as well as genetic analysis of Knowing the roles of signaling molecules and embryonal cells () before its transfer transcription factors has allowed better into the uterine cavity. The birth of the world's understanding of the mechanism of processes first “test tube baby” in 1978 significantly during the development and the origin of contributed to the development of clinical congenital anomalies. However, in the curricula embryology. Both a British gynecologist Patrick of medical schools, there is often larger space for Steptoe (1913-1988) and a physiologist Sir other courses such as molecular , Robert Edwards (1925-2013) took credit for , , and often at the developing methods of in vitro fertilization. A expense of morphological sciences (Grim, 2009). clinical embryologist is a close co-worker to a Embryology teaching varies considerably not only gynecologist. Embryologists in the centers of between countries but also between different reproductive medicine, among other activities, universities (Moxham et al., 2016). For instance, are responsible for the examination of the in the USA, embryology is usually taught together ejaculate and semen analysis (spermiology), for with gross anatomy (integrated courses) (Drake the course of in vitro fertilization (e.g. using et al., 2002), while in most medical schools in micromanipulation techniques), for evaluation of Slovakia or the Czech Republic it is taught in adequacy of the early embryonic development conjunction with histology. Alternatively, there are and in the case of pre-implantation genetic curricula in which it is a completely separate screening for taking the daughter cells stand-alone course. In general, we can say that (blastomeres) from the . Following recently there has been observed a trend of relevant training and exams, clinical embryolog- reducing the number of hours devoted to ists can obtain an internationally recognized embryology, including laboratory hours in certificate from the European Society of Human embryology courses (Drake et al. 2009). If Reproduction and Embryology (Kovacic et al., embryology is taught only in the lower years of 2015). medical studies, students often poorly underst- and and underestimate the clinical importance of 6. Modern Trends in Embryology, “Molecular this scientific field. It is, therefore, desirable to Embryology” and Regenerative Medicine add to the curriculum also lectures on "clinically As another application of embryological oriented embryology" in later years of the medical knowledge into clinical practice can also be program (Scott et al., 2013; Hamilton and regarded the study of knowledge of Carachi, 2014). and reparation mechanisms. In fact, these Based on my opinion, very useful and high- mechanisms are at the molecular level often quality recommendations for a core syllabus for similar to activities which take place during the embryology teaching were published by embryonic development. For example, signaling Fakoya et al. (2017). The question is: how can be pathways responsible for the formation of new embryologic information presented effectively to blood vessels during embryonic development medical students? Different curricular models in also apply during tissue regeneration and embryology teaching exist, but at most medical remodeling in the postnatal period, as well as in schools, embryology is presented as a lecture- the formation of new blood vessels in tumors based course, typically with no laboratory (Kyselovič and Varga, 2017). Similarly, without (Carlson, 2002). Adequate textbooks and the knowledge of genes and signaling molecules computer-based learning programs are extremely of the migration of -derived cells helpful in teaching. The advantage is when they during embryogenesis, it is not possible to contain test questions for final verification of

50 Direc. Nac. de Derecho de Autor Reg. Nº: 5291682 www.anatclinar.com.ar Embryology Teaching Rev Arg de Anat Clin; 2017, 9 (2): 47-51 ______knowledge or problem-based model situations in processes and physical exercises. Ann Transl the context of the clinical problems. Some Med 5: S20. authors (e.g. Nieder et al., 2005; Vasan et al., Moxham BJ, Emmanouil-Nikoloussi E, Standley 2008; Shankar and Roopa, 2009) recommend H, Brenner E, Plaisant O, Brichova H, Pais D, "team-based learning" (independent out-class Stabile I, Borg J, Chirculescu A. 2016. The preparation for in-class discussion in small attitudes of medical students in Europe toward groups). More than 80% of students agree that the clinical importance of embryology. Clin team-based learning is helpful to their learning. Anat 29: 144-50. In conclusion, it is to be hoped that embryology, Nieder GL, Parmelee DX, Stolfi A, Hudes PD. either as part of other courses or as a stand- 2005. Team-based learning in a medical alone course, will not cease to exist at medical gross anatomy and embryology course. Clin schools. And future physicians worldwide will still Anat 18: 56-63. receive information on this "pillar" of under- Obladen M. 2017. Animatio: a history of ideas on graduate medical courses with a significant the beginning of personhood. J Perinat Med. impact on clinical practice. doi: 10.1515/jpm-2016-0404. Olsson L, Levit GS, Hoßfeld U. 2017. The "Biogenetic Law" in : From Ernst References Haeckel's formulation to current approaches. Carlson BM. 2002. Embryology in the medical Theory Biosci 136: 19-29. curriculum. Anat Rec 269: 89-98. Rink BD, Norton ME. 2016. Screening for fetal Drake RL, Lowrie DJ Jr, Prewitt CM. 2002. aneuploidy. Semin Perinatol 40: 35-43. Survey of gross anatomy, microscopic Scott KM, Charles AR, Holland AJ. 2013. Clinical anatomy, , and embryology embryology teaching: is it relevant anymore? courses in curricula in the ANZ J Surg.; 83: 709-12. United States. Anat Rec 269: 118-22. Shankar N, Roopa R. 2009. Evaluation of a Drake RL, McBride JM, Lachman N, Pawlina W. modified team based learning method for 2009. Medical education in the anatomical teaching general embryology to 1st year sciences: the winds of change continue to medical graduate students. Indian J Med Sci.; blow. Anat Sci Educ 2: 253-59. 63: 4-12. Fakoya FA, Emmanouil-Nikoloussi E, Sharma D, Shepard TH, Barr M Jr, Brent RL, Hendrickx A, Moxham BJ. 2017. A core syllabus for the Kochhar D, Oakley G, Scott WJ Jr, Rogers teaching of embryology and teratology to JM. 2010. An updated history of the medical students. Clin Anat.; 30: 159-67. Teratology Society. Birth Defects Res A Clin Friedman JM. 2010. The principles of teratology: Mol Teratol 88: 263-85. are they still true? Birth Defects Res A Slavikova T, Zabojnikova L, Babala J, Varga I. ClinMolTeratol.; 88: 766-68. 2015. An embryological point of view on Grim M. 2009. Anatomy in perspective of modern associated congenital anomalies of children time. Czech Medical Academy Review 5:16- with Hirschsprung disease. Bratisl Med J 116: 19. 640-47. Hamilton J, Carachi R. 2014. Clinical embryol- Van den Veyver IB. 2016. Recent advances in ogy: is there still a place in medical schools prenatal genetic screening and testing. today? Scott Med J 59: 188-92. F1000Res 5: 2591. Kachlik D, Musil V, Baca V. 2016. Contribution to Van Speybroeck L, De Waele D, Van de Vijver G. the anatomical nomenclature concerning 2002. Theories in early embryology: close general anatomy and anatomical variations. connections between epigenesis, pre- Surg Radiol Anat 38: 757-65. formationism, and self-organization. Ann N Y Kitagawa H, Pringle KC. 2017. Fetal surgery: a Acad Sci 981: 7-49. critical review. Pediatr Surg Int 33: 421-33. Vasan NS, DeFouw DO, Holland BK. 2008. Kovacic B, Plas C, Woodward BJ, Verheyen G, Modified use of team-based learning for Prados FJ, Hreinsson J, De los Santos MJ, effective delivery of medical gross anatomy Magli MC, Lundin K, Plancha CE. 2015. The and embryology. Anat Sci Educ 1: 3-9. educational and professional status of clinical embryology and clinical embryologists in Acknowledgments Europe. Hum Reprod 30: 1755-62. This study was supported by Grant of the Slovak Kyselovič J, Varga I. 2017. Research focused on Research and Development Agency No. APVV- microRNAs: a link between myocardial 0434-12 and Grant of the Ministry of Education of remodeling and growth during pathological the Slovak Republic VEGA 1/0086/17.

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