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Editorial
EMBRYOLOGY TEACHING: AN OFTEN-NEGLECTED PART OF THE
MEDICAL CURRICULUM
Ivan Varga
Institute of Histology and Embryology, Faculty of Medicine, Comenius University in
Bratislava, Slovak Republic
Embryology is a science of the origin and
development of living organisms. The study of
human embryology has theoretical (as a preclinical
course during medical study), but also
important clinical significance. Embryology is a
fascinating field of science which can guide
students of medicine or natural sciences in a
miraculous way through the laws of human
development from fertilization to birth. Owing to
embryology, we get to know ourselves because
we all went through this period of development
(although we do not remember it). This issue will
again capture our attention or has already done it
in time when we are about to become parents or
grandparents, and we will be interested in the
development of our children or grandchildren.
Regarding medical studies, embryology facilitates
the study of anatomy as it can also explain the
emergence of anatomical variations, anomalies.
The knowledge of embryology is also beneficial
for medical students in the preparation for the
exam in Gynecology and Obstetrics (infertility
disorders and assisted reproduction techniques,
structure and function of the placenta, the factors
affecting the development of the embryo), 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
scientists to think about when a new human life
starts. An ancient Greek philosopher Aristotle
(384-322 B.C.) predicted that a developing
individual does not have its own soul in the early
stages of development (fetus inanimatus,
unsouled fetus). At the beginning of development,
it has only a vegetative and later animal
soul, and it is, therefore, similar to plants and
lower animals. He was based on his theory of
epigenesis in which single organs of an individual
develop from a simpler to more complex form.
With some modifications, the concept of delayed
ensoulment - at 40 or 90 days after fertilization was
adopted for example by Saint Thomas
Aquinas and remained valid throughout centuries
(Obladen, 2017). Basic processes that today we
refer to as fertilization and subsequent early
development were previously ambiguous (it was
a period without a quality light microscope). On
the one hand, there was Aristotelian theory of
epigenesis, i.e. the theory of gradual evolution of
individual organs. On the other hand, there was
formed the theory of preformationism under
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which the already finished miniature organism
was hiding inside the germ cells. There were two
competing models of preformationism: ovism and
spermism (animalculism). According to ovists, a
woman's oocyte is the essence of a new
individual, whereas the sperm only serves to start
the developmental process. The father of ovist
preformationism is an English physiologist
William Harvey (1578-1657) who asserted "omne
vivum ex ovo" (all life begins from an egg). In
contrast, there were animalculists, e.g. the
inventor of the light microscope Dutchman
Antony van Leeuwenhoek. Leeuwenhoek (1632-
1723) together with his colleague Ham first
observed by light microscopy sperm and believed
they saw in its head a preformed human being
(so-called homunculus). Primitive preformed
opinions were revised in the 18
th
century by a
German-Russian physiologist and one of the
founders of embryology Caspar Friedrich Wolff
(1733-1794). Wolff in his dissertation "Theoria
Generationis" revived and supported Aristotle's
theory of epigenesis. He assumed that the
gradual development of an individual is controlled
by a kind of “vis essentialis", i.e. life or formative
force (Van Speybroeck et al., 2002).
Embryology as a modern science began to
develop after the discovery of a light microscope.
Thanks to the development of microscopic
techniques, a German-Latvian biologist Heinz C.
Pander (1794-1865) managed to describe the
three germ layers in the chick embryo. The
presence of germ layers also in other animal
species was confirmed by an Estonian scientist
Karl Ernst von Baer (1792-1876). In 1842, Von
Baer formulated the basic laws of embryogenesis,
including for example a postulate that
the general structural relations are likewise
formed before the most specific appear (e.g. the
skin has in embryogenesis the equal basis in all
vertebrates, and only later there are formed
scales, feathers, or hair).Von Baer laws were the
basis also for publishing the work of an English
biologist Charles Darwin (1809-1882), entitled
"On the Origin of Species" (1859). Darwin's
theory of evolution influenced many scientists,
such as a German biologist Ernst Haeckel (1834-
1919). His work "Anthropogenie" (1874) is often
considered as one of the first textbooks of
embryology.
This historical overview also shows that
embryology has always been at the center of
concerns of physicians and natural scientists. But
what is the current status of embryology at
medical schools? There are several reasons why
embryology is an appropriate component of the
standard medical curriculum. These reasons are
equally important, so their order is more or less
random.
1. Embryology as Part of Biological Sciences
Embryology provides evidence for the
development of man as a result of the evolution
of the animal kingdom. Embryonic development
of man is a condensed and abbreviated repetition
of the continued gradual evolutionary development
of the whole subphylum of vertebrates,
even the entire animal kingdom. Vertebrates
resemble each other in the early stages of
embryonic development and differences appear
along with their gradual embryonic development.
This rule was first noticed by Ernst Haeckel, and
he named it as the recapitulation theory, or
biogenetic law (ontogeny recapitulates
phylogeny) (Olsson et al., 2017). Even in the
development of man, there could find many
examples that confirm Haeckel's hypothesis. We
cite the following examples:
 the presence of branchial (pharyngeal)
arches on the cranial end of the embryo
during the 4th and 5th week of development
that resemble gills of aquatic animals
 the gradual emergence of all stages of
kidney development (pronephros, mesonephros,
and metanephros) also in humans,
while some were characteristic only for fish or
amphibian
 the development of the cloaca as the
common end portion of the digestive and
urogenital system, typical of the class of
animals from fishes to birds
 the morphology of the developing heart
also reminds the heart of particular classes of
animals (the embryonic heart tube with its
inflow and outflow portion is similar to the
heart of fishes, etc.)
 the formation of somites reminds
segmented body structure (segmentation) of
some invertebrates and vertebrates
 the hematopoietic function of the liver
and spleen during the intrauterine development
reminds the function of these organs
in those animals (fish and amphibian larvae)
that have no bone marrow yet
At this point, I would like to remind the words of a
giant of Czech embryology, Professor Jaroslav
Slipka, MD, DSc. (1926-2013): "Every tissue or
organ has their own history. History has two
faces - ontogenesis and phylogenesis. Both are
equally important."
2. Relevance of Embryology to the Study of
Anatomy
Another important function of embryology is to
provide a logical basis for understanding the
overall organization of the human body.
Embryology describes the development of the
body organs of the adult and explains the
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emergence of possible variations in their number,
changes to final position or topographic particularities
of human anatomy (variant anatomy). The
variant anatomy is a specific large subfield of
gross anatomy. Anomalies of the human body
which are not considered as serious defects of
the development that means they do not impair
the function are considered as variants (Kachlik
et al., 2016). Especially in the areas of surgery
and radiology, it is important to think about the
possible anatomical variations, and therefore it is
important to understand the laws of embryology
for each clinical discipline.
3. Relevance of Embryology to Prenatal
Diagnosis
Modern embryology deals not only with
morphogenesis - the development of organs but
also with various developmental disorders that
result in birth defects (congenital anomalies).
First and foremost, an obstetrician and
pediatrician should be thoroughly familiar with the
human development before birth. Every doctor
encounters congenital anomalies in their practice.
A precondition for recognizing birth defects,
understanding their formation during development
and often a successful treatment is the
understanding of the normal development of man
before birth. Improving the methods of prenatal
diagnosis (amniocentesis, ultrasound, fetoscopy,
biochemical screening or analysis of free fetal
DNA from maternal blood) allows early detection
of many birth defects, identify their causes and by
novel operating procedures, it is sometimes
possible also to remove the consequences (Rink
and Norton, 2016; Van den Veyver, 2016). To
date, there has been a range of developmental
anomalies that can be corrected during the fetal
period in the uterus (so-called fetal surgery). In
fact, the wounds after such surgery heal much
better in utero; however, the development of fetal
surgery is still limited by financial, technical, and
professional demands of the performance and by
a high risk for subsequent preterm delivery
(because the human amnion does not heal,
leading to a significant incidence of premature
rupture of the membranes) (Kitagawa and
Pringle, 2017). In the future, there might also be
possible the correction of the identified
chromosomal fetal anomalies (gene therapy), or
there will be more extended also a replacement
therapy with the administration of products of
defective genes (e.g. enzyme replacement
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 nature 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 Teratology Reviewed by Friedman (2010)
4. Embryology and Understanding of
Congenital Anomalies
A scientific discipline teratology (from Greek
teratos - monster, malformation) deals with the
causes of congenital defects. It is important to
know harmful teratogenic factors and their effects
on the developing organism at certain periods to
produce healthy offspring. On the other hand,
nowadays, there is already evidence of the
embryo-protective effect of certain vitamins (such
as folic acid) whose intake in natural form is not
usually sufficient. The principles of teratology
were published in 1959 by James G. Wilson
(1915-1987). He expanded the original five
principles in 1977 to six (Table 1). Teratology
uses the methods of experimental embryology
(based on animal models), develops test
methods for embryo-toxicity on tissue cultures
and aids to discover the causes of serious
developmental malformations. Over the past 50
years, the Teratology Society (USA) has also
developed the scientific basis to prevent birth
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defects caused by rubella and alcoholism, as well
as other prenatal exposures (Shepard et al.,
2010).
5. Clinical Embryology and Reproductive
Medicine
With the development of methods of reproductive
medicine, there specifically developed also a new
laboratory discipline, clinical embryology.
Assisted reproduction is a medical discipline that
deals with oocytes, sperm and embryos outside
the body (in vitro) aimed at a woman to get
pregnant (infertility treatment). Currently, the field
of reproductive medicine includes also the issues
of freezing of gametes and embryos (cryopreservation),
as well as genetic analysis of
embryonal cells (blastomeres) before its transfer
into the uterine cavity. The birth of the world's
first “test tube baby” in 1978 significantly
contributed to the development of clinical
embryology. Both a British gynecologist Patrick
Steptoe (1913-1988) and a physiologist Sir
Robert Edwards (1925-2013) took credit for
developing methods of in vitro fertilization. A
clinical embryologist is a close co-worker to a
gynecologist. Embryologists in the centers of
reproductive medicine, among other activities,
are responsible for the examination of the
ejaculate and semen analysis (spermiology), for
the course of in vitro fertilization (e.g. using
micromanipulation techniques), for evaluation of
adequacy of the early embryonic development
and in the case of pre-implantation genetic
screening for taking the daughter cells
(blastomeres) from the morula. Following
relevant training and exams, clinical embryologists
can obtain an internationally recognized
certificate from the European Society of Human
Reproduction and Embryology (Kovacic et al.,
2015).
6. Modern Trends in Embryology, “Molecular
Embryology” and Regenerative Medicine
As another application of embryological
knowledge into clinical practice can also be
regarded the study of knowledge of regeneration
and reparation mechanisms. In fact, these
mechanisms are at the molecular level often
similar to activities which take place during
embryonic development. For example, signaling
pathways responsible for the formation of new
blood vessels during embryonic development
also apply during tissue regeneration and
remodeling in the postnatal period, as well as in
the formation of new blood vessels in tumors
(Kyselovič and Varga, 2017). Similarly, without
the knowledge of genes and signaling molecules
of the migration of neural crest-derived cells
during embryogenesis, it is not possible to
understand the concomitant occurrence of large
intestine motility disorders (e.g. Hirschsprung
disease) with congenital defects of the urinary
system and the heart (Slavikova et al., 2015).
Quo Vadis Embryology Teaching?
This overview also shows that embryology is not
a closed static field with a set of stable and
unchangeable knowledge. Embryology is growing
by the development of biological sciences, like all
branches of medicine, and must, therefore,
respond to ever increasing range of knowledge
also in the curriculum. Today, modern embryology
examines the development of man from the
macroscopic description up to gene expression.
Knowing the roles of signaling molecules and
transcription factors has allowed better
understanding of the mechanism of processes
during the development and the origin of
congenital anomalies. However, in the curricula
of medical schools, there is often larger space for
other courses such as molecular biology,
immunology, biochemistry, and often at the
expense of morphological sciences (Grim, 2009).
Embryology teaching varies considerably not only
between countries but also between different
universities (Moxham et al., 2016). For instance,
in the USA, embryology is usually taught together
with gross anatomy (integrated courses) (Drake
et al., 2002), while in most medical schools in
Slovakia or the Czech Republic it is taught in
conjunction with histology. Alternatively, there are
curricula in which it is a completely separate
stand-alone course. In general, we can say that
recently there has been observed a trend of
reducing the number of hours devoted to
embryology, including laboratory hours in
embryology courses (Drake et al. 2009). If
embryology is taught only in the lower years of
medical studies, students often poorly understand
and underestimate the clinical importance of
this scientific field. It is, therefore, desirable to
add to the curriculum also lectures on "clinically
oriented embryology" in later years of the medical
program (Scott et al., 2013; Hamilton and
Carachi, 2014).
Based on my opinion, very useful and highquality
recommendations for a core syllabus for
the embryology teaching were published by
Fakoya et al. (2017). The question is: how can be
embryologic information presented effectively to
medical students? Different curricular models in
embryology teaching exist, but at most medical
schools, embryology is presented as a lecturebased
course, typically with no laboratory
(Carlson, 2002). Adequate textbooks and
computer-based learning programs are extremely
helpful in teaching. The advantage is when they
contain test questions for final verification of
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knowledge or problem-based model situations in
the context of the clinical problems. Some
authors (e.g. Nieder et al., 2005; Vasan et al.,
2008; Shankar and Roopa, 2009) recommend
"team-based learning" (independent out-class
preparation for in-class discussion in small
groups). More than 80% of students agree that
team-based learning is helpful to their learning.
In conclusion, it is to be hoped that embryology,
either as part of other courses or as a standalone
course, will not cease to exist at medical
schools. And future physicians worldwide will still
receive information on this "pillar" of undergraduate
medical courses with a significant
impact on clinical practice.
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Acknowledgments
This study was supported by Grant of the Slovak
Research and Development Agency No. APVV-
0434-12 and Grant of the Ministry of Education of
the Slovak Republic VEGA 1/0086/17.