Introduction to Embryology Carolyn Joy Rodgers MD FACOG

AIM Begin your study of embryology Outline the early major developmental events and anatomical landmarks of a human embryo Understand and be able to use the terminology of early human development Act as an introduction to the systems embryology you will encounter in the phase one modules Begin to identify relevance of these processes to clinical practice Develop a glossary of new words. Some of you may be familiar with many depending on your background

Learning Outcomes: lecture one Describe simply the processes from fertilisation to implantation Describe simply the second week of human development Describe simply the early stages of placental development First will be developed further in REPRO module Second week of development is the first week in the uterus Placental is that amazing organ that nourishes and supports the growing pregnancy as well as providing mechanisms for excretion of waste. As we shall see in the Repro module it has other significant roles as well.

What is embryology? Development from single diploid cell…. to…. Multicellular organism Organised body structure Specialised tissues THE complex structure that results is recognisable as a human being The specialised tissues, once developed will grow and mature along different lines

Development Growth Morphogenesis Differentiation Change in size by cell division and elaboration of products Change in shape/ form involves mass cell movement / migration as well as cell interactions. The term induction is used whereby one group of cells produce a signal to which another group of cells respond and change. Many of these inductive processes occur in human development. Differentiation is the specialisation of cells into tissues/ organs and ultimately body systems

Role and relevance of embryology Understand normal body structure Maturation of adult structures Anatomical relationships Links prenatal development to clinical medicine Values in medicine Often thought of as somewhat dry subject but: Helps us in understanding normal anatomy of baby/child and the changes as we mature into adults;, and to understand the spectrum of variation in anatomy Helps us understand relationships between organs and body systems eg why does my uterus drain lymph to my iliac nodes but my ovaries drain lymph to my lumbar nodes Links our lives before birth to the rest of our lives and allows for better fetal / reproductive health, better obstetric care, less birth defects and in some cases better long term health as in utero events can have long lasting effects on our lives and well being It can also help us as individuals and societies grapple with some of the issues hat challenge us, abortion rights, fetal surgery, fetal screening, pre-implantation diagnosis, designer baby, and the role of ART in infertility cases

How is it studied? Starting with anatomy Teratology Experimental Molecular / Cellular Genetic Anatomical studies dominated the field initially –dissection techniques and improved optical instruments helped. They investigated offspring with birth defects comparing them to normal offspring and this study is called Teratology In 20th C dyes and radiographic techniques advanced the study and in the 60s the early genetic markers were used in studying embryos Teratolgy became prominent in the 60s largely because of the thalidomide issue ( association bdrug used as an anti-nausea agent in pregnancy and abnormality in limb development) Today molecular approaches are used to identify and tag cells with various probes to map the fate of specific cells during development and techniques to alter specific gene expression have allowed us to study the role of a single gene in development of a specific tissue/. Some of you are probably quite familiar with some of these techniques… but for now But we are going to stay largely at the simple anatomy

The embryonic period Conception Eight weeks Body axes Organ primordia Three layers Early placenta Embryonic period usually covers first 8 weeks From creation of the new individual to a structure that is recognisable as a human- has distinct shape and obvious body axes ( not just a blob) Which has all the basic structural building blocks, Which has necessary precurser cell types three types from which all others will devlop And has the beginning of an organ designed to nurture its further devlopment

First Week Fertilisation Cleavage Blastocyst formation Implantation These are the events we’ll look at. Much of first week is spent in the oviduct

The first day Gametes and fertilisation-zygote A unique new individual Ampulla Cleavage Blastomeres Male and female haploid gametste fuse their nuclei in the fertilisation process to create a new diploid individual .. The zygote Usually in the ampulla of the oviduct, then it gradually makes its way alomg the oviduct toward the uterus Gametogenesis is a whole topic itself which we will cover in Repro but suffice it to say that individuals produce these haploid cells by a process of meiotic cell division. It is thought that there is quite a high frequency of meiotic errors especially in women as we get older. Difficult to estimate numbers of abnl zygotes as most are lost during first 1-2 weeks and woman may never know she was pregnant. Some authers think upto 50% zygotes are lost and half may be due to chromosome abnl- a natural method of reducing incidence of congenital birth defects mRNA inherited from oocyte supports embryo development through fertilisation and early cleavage- a series of mitotic cell divisions to produce a clump of identical cells Onset of mRNA production from embryonic genome principally at 4-8c stage

Ovum is a large cell. Sperm head has to penetrate through outer shell, zona pellucida by enzymic action

Day 3 Compaction Morula This process begins to segrate outer cells and inner cells in the clump as cleavage carries on to produce a 16 cell ball mulberry

Entering the uterus: day 4-5 Blastocoele / Blastocyst Outer cells-Trophoblast- Inner cell mass-embryoblast -pluripotent Morula begins to enter uterine cavity. Fluid begins to penetrate between the cells until a confluent cavity blastocoele forms and the structure is called a blastocyst. The inner cell mass is now termed the embryoblast and will become the embryo proper- cells are pluripotent- can form virtually any cell or tissue– Whole field of study about the potential use of embryonic stem cells in curing a number of disease Also gives the early embryo some compensatiory power-if part lost can regrow, all or nothing effects of chemicals, radiations and other insultsetc

Implantation:day 6-7 Hatching Cytotrophoblast Syncytiotrophoblast Invasion New individual is finally in the uterus- now it needs to latch on. First of all it escapes from the ZP Then the trophoblast which has differentiated into outer syncytio( multinucleate cell mass) and inner cyto ( discrete cells) begins the process of implantation. It

Implantation process:day7 Uterus has been prepared Usually in upper part of uterus Specific orientation and maternal/embryonic communication mechanisms Immunologically complex Very little information in humans IVF- most likely stage of failure Uterus has been prepared by events of the menstrual cycle-more in REPRO Usually in the upper part of uterus-you might want to consider why Very complex / invasive process Another stage of pregnancy failure Consider here ART- men and women have gone thru all the counselling, hormone preps, retrievals etc then to lose at this stage

Second week Two layers Amniotic cavity Yolk sac Extraembryonic mesoderm-splanchnic - somatopleural So, implantation is proceeding and the second week begins. Remember the timeline is only a guide– there can be quite a bit of difference in rates of development even at these early stages Main events of the second weekare- formation of two distinct layers in the embryoblast, the formation of the cavities– week of twos

The two layers: Bilaminar disc: day8-9 Epiblast and hypoblast Amniotic cavity Primitive yolk sac Blastocyst is partly embedded, fibrin plug begins to form at the site. Cells of the embryoblast now differentiate into two layers, hypoblast and epiblast They form a flat disc with the hypoblast adjacent to the blastocyst cavity. A small cavity then begins to form in the epiblast and this will form the amniotic cavity Meanwhile cells from hypoblast produce a membrane which lines the cytotrophoblast of the blastocoele and it becomes the primitive yolk-sac

Day 10-12 Utero-placental circulation Extra-embryonic mesoderm Chorionic cavity (Extra-embryonic coelom) Blastocyst becomes completely embedded. Trophoblast continues to grow especially at the embryonic end. Vacuoles appear and fuse into larger spaces,- lacunae- and cells of syncytio penetrate deep into uterine stroma and erode into congested uterine capillaries- sinusoids- establishing contact with maternal circulation Anew group of cells, a loose connective tissue type, the EEM appears between the cyto and yolk-sac and splits into splanchnic layer and somatopleural layer Large spaces begin to form in the EEM and these coalesce to form the chorionic cavity

Day 13-14 Implantation bleed Human chorionic gonadtrophin HCG Villous formation Secondary yolk sac Chorionic plate Connecting stalk All this has happened before she misses a period, SOMETIMES IMPLANTATION BLEED due to maternal blood filling lacunae may be mistaken as period—wrong dates Trophoblast continues to grow with finger like projections Hcg The chorionic cavity surrounds the the primitive yolk sac and amniotic cavity except where the bilaminar disc is connected to it by connecting stalk destined to be the umbilical cord 1)