{Part I described how we Came Into Being, and how we spent our very earliest moments. Part II herein is about our Earliest Days. These are extracts from a larger work on embryology and bioethics, researched and completed in September 2021. This essay constitutes the first half Section 2 of that work. The next part addresses Embryonic Engineering}
Section II: Homo sum
“The deeper you go into biology, the more it shades into something that appears to be religious”
Jordan Peterson, March 2021, before he received the grace to accept that it’s quite alright to be terrified that the mythological narrative world and the real historic objective world do touch, and it is those who surrender to that terror and strive to live up to the Ideal despite their weakness, who are the saints.
Embryo
The embryo stage refers to the early development period in multicellular organisms and the term is derived from the Greek embruon meaning “the young one”. In many multicellular organisms, "embryo" can be used more broadly to refer to any early developmental or life cycle stage prior to birth or hatching. Human embryology is the study of human ontogeny in the first 8 weeks of our lives beginning with our origination usually within the process of fertilisation and ending when more than 90 percent of the 4500 identifiable structures of the adult body have appeared and we assume the name of foetus, which also means “the young one” but originates from Latin. The division of human development into an embryonic or embryo and foetal or foetus periods is historical and arbitrary, based on an observation of the replacement of cartilage in the humerus with bone marrow. The first eight weeks constitute the embryonic period of human development and embryonic development begins when the embryo begins and that is at the earliest stages in the process of fertilisation, and continuous growth and development proceed thenceforth through recognisable stages. When we are born, we will be called infant, even if we are born prematurely.
First Journey
Consequent to syngamy, and the formation of the first mitotic spindle, we undergo our first cleavage within a day or a little longer and each new cell is called a blastomere. Two become three and we become multi-cellular as we move towards the uterine cavity. When we have 8 cells or more on day 3, there is a tightening and realignment between adjacent cells and a polarisation between inner and outer blastomeres become visible. We may be called a morula towards the end of our third day because we look like a mulberry consisting initially of 16-32 blastomeres. From around the fourth day a fluid-filled cavity begins to form within, and we are named blastula or blastocyst and a distinction between our outer layer of trophoblasts and an inner cell mass of pluripotent blastomeres referred to misleadingly as embryoblasts becomes apparent. During our fifth day, our blastocystic cavity the blastocoele continues to enlarge, our cells continue to multiply and the inner cell mass begins to differentiate.
Implantation
Each of us move and develop at our own pace, and usually by our fifth day, having completed the journey along the Fallopian tube, we enter the lumen of the uterus and hatch out herniating through an opening on the zona or now capsula pellucida and expanding so that we may embed in mother’s endometrium. The inner cell mass begins to specialise into epiblast that in turn gives rise to the hypoblast which together form a double-layer disc. Our trophoblasts further differentiate into the cytotrophoblast and the outer synctiotrophoblast which derives from it, and which initiates the process of placentation. By the day 6 while we begin settling into mother’s uterine wall that is already prepared via decidualisation and made hospitable for receiving us, having rotated to align our inner cell mass to be adjacent to the endometrium and benefitting from integrin-mediated adhesion. This first attachment is called adplantation and indicates the onset of implantation. During this time and into the following day our didermic disc separates the blastocoele from the emerging amniotic cavity. Our synctyotrophoblast forms the syncytium which causes apoptosis of the endometrial epithelium enabling penetration into the stroma beneath and into maternal blood capillary walls by the seventh day.
While our amniotic cavity is expanding, a layer of amnioblast cells is formed from differentiating epiblasts, that separate it from the cytotrophoblast on day 8. Early in our second week extracellular vacuoles appear in the syncytium which join to form lacunae that get filled with uterine secretions and further to rupturing of maternal capillaries are filled with maternal blood. By the ninth day the hypoblasts have also multiplied and grow ventrally along the inner side of the blastocystic cavity. We are now entirely embedded within the endometrium, and the syncytium has grown to surround the cytotrophoblast. By the tenth or eleventh day while the lacunae network expands, the hypoblasts extend completely to form the wall of what is called the primary umbilical vesicle, exocoelomic cavity or yolk sac which replaces the blastocystic cavity and that facilitates preplacental nutrition and gas exchange - and which in turn becomes surrounded by a fine exocoelomic membrane, that by day 11 develops into a short-lived reticulum of acellular material.
It is yet to be confirmed whether it is hypoblast cells from the extracoelomic membrane or epiblasts and cytotrophoblasts, that differentiate into cells referred to as “extra-embryonic” mesoblasts - and it appears likely that they both do, but in varying degrees at different stages of our development, that give rise to a new chorionic cavity in place of the reticulum, that lies between the umbilical vesicle and the cytotrophoblast. By day 12, implantation is complete and the invasive growth of the syncytium ceases. By day 13 the umbilical vesicle has transitioned into the secondary umbilical vesicle, the localised thickening of hypoblast that is the prechordal plate is formed and an arterial inflow and venous outflow system is established for obtaining mothers blood to continue to nourish us and take away waste products and the primitive utero-placental circulatory system has arisen. By day 13 the chorionic cavity is surrounded by a layer of mesoblast cells forming its walls that cover the inner side of the cytotrophoblasts layer and the outer sides of the umbilical vesicle and amniotic cavity, the chorion itself being a double-layered membrane formed by the trophoblast and the “extra-embryonic” mesoderm.
As the generation of the embryo occurred during a moment in the process of fertilisation, likewise the development of the embryo continues during the movement into the uterine cavity and during the process of implanting into the uterus, extending from the onset through the embedment to the completion of implantation. Development and change continue thereafter during the remaining pre-natal period whether pre- or post-gastrulation and during foetogenesis, and thereafter after birth, through childhood, youth and adulthood. Even though obvious, it needs to be stated that the pre-implantation period of embryonic development ends with the completion of implantation on day 12, but our growth and development continue unabated. By day 14 we are constituted of a bi-layer disc surrounded by the amniotic cavity, the umbilical vesicle and the chorionic cavity that is attached by a thick stalk to the chorion, within the syncytium, which itself is surrounded by maternal decidual cells.
Gastrulation and Beyond
Prior to gastrulation a subpopulation in the proximal posterior region of the epiblast initiates the expression of the transcription factor protein T/Brachyury thus defining the site of gastrulation. Migrating epiblasts which initially appear as a linear grooved band of cells called the primitive streak by around day 14 which marks the onset of gastrulation, ingress early in our third week into the primitive groove and at the primitive pit within the primitive node at its cranial end to begin forming a third germinal layer called the “intra-embryonic” mesoderm between the two existing layers that constituted the bi-laminar disc. During this time, these mesenchymal cells migrating through the primitive knot begin forming the notochord that establishes a central body axis, and the buccopharyngeal and cloacal membranes which will be our future mouth and anal cavities appear. Consequently, epiblast and hypoblast are replaced with epiblast-derived ectoderm and endoderm, the now trilaminar embryonic disc thickens and we could be called a gastrula by day 19.
Induced by the notochord, neurulation also begins in our third week with the formation of the neural tube out of neural tissue differentiated from the ectoderm and a transient neurenteric canal appears connecting the amniotic cavity to the primitive gut that is the umbilical vesicle, and organogenesis begins - and proceeds and continues after birth as well, while a finger-like outpocketing of the posterior wall of the umbilical vesicle develops into the allantoic diverticulum, a primitive excretory duct of the embryo that will become part of the urinary bladder. Beginning in the third week and continuing into the fourth, somitomeres that will form transitional organs called somites appear from paraxial mesoderm, our umbilical vesicle folds to close off the body cavity and form the gut by day 22 and the disc takes on a cylindrical shape in transverse view or head on, and a convex shape from a rostral-caudal view, or when seen sideways. Our heart is the first functional organ with cardiac pulsation in the primitive heart tube beginning on day 21 or 22, the maturation of the heart having begun in the early stages of gastrulation on day 15 with migration into regions known as heart fields of mesodermal cells that specialise into myocytes.
As the placenta, formed by the chorion on the embryonic side, takes over our nourishment beginning week 4, the umbilical vesicle reduces in size having begun to vascularise on day 17 giving rise to erythroid precursors and remaining to serve in haematopoesis - and harbouring in its wall our primordial germ cells which will give rise to our gametes, at the base of the allantois. During all this time, our continuous and multi-faceted growth in size, complexity and capability continue marvelously as it has done from our beginning, and continues to do likewise at the end of our eighth week when we are kicking and capable of jumping when startled as we graduate from embryohood, into a time when we become able to respond to music that mother is listening to, and even later when we change environment and emerge to breath the air, and at all other milestones we pass after that as well.