Early Development

Main Anatomy Index | The placenta

This page was contributed by David Boshell, with thanks to Sarah Yong

Click here to go to Spermatogenesis under the Male Reproductive System

The First Week

• The process of fertilisation occurs as follows: a spermatazoon encounters a receptor protein in the zona pelucida of an oocyte, penetrating this layer by releasing degradative acrosomal enzymes.
• The cell membranes of the 2 gametes fuse, causing:
  1. The release of cortical granules from under the oocyte membrane that will render the zona pellucida impenetrable to further sperm, preventing polyspermy
  2. The oocyte to resume its second meiotic division, becoming the definitive oocyte, and the male and female pronuclei fuse to produce a single, diploid (2N) nucleus of the fertilised zygote.

• Over the next few days, the zygote, travelling down the oviduct, will undergo cleavage to produce blastomeres, still enclosed in the zona pellucida, and by day 4 consists of about 32 cells, now known as the morula.
• At about the 8 cell stage, the blastomeres develop an inside-outside polarity, undergoing compaction to maximise cell to cell contact, and segregation occurs between the central and peripheral blastomeres, forming the inner cell mass and outer cell mass, respectively.
• The inner cell mass will give rise to most of the embryo proper, and is thus known as the embryoblast, whilst the outer cell mass will contribute to the placenta and is called the trophoblast.
• By day 5, fluid absorbed by the morula forms the blastocyst cavity, so the embryo is now called the blastocyst, and the embryoblast cell mass at one side of this cavity forms the embryonic pole, with the opposite side being the abembryonic pole.

• The morula reaches the uterus by about day 4, hatches from the zona pellucida by day 5, adheres to the uterine lining, and implants in the uterine wall on about day 6.
• The adjacent endometrial cells respond to the presence of the blastocyst and progesterone secreted by the corpus luteum by undergoing the decidual reaction to differentiate into secretory decidual cells, whilst the uterine wall and its glands become oedematous and vascularised.
• The supply of progesterone is maintained by cells of the trophoblast secreting human chorionic gonadotropin (hCG) that supports the corpus luteum.

• Implantation in an abnormal site, such as the oviduct or peritoneal cavity results in an ectopic pregnancy.

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The Second Week

• The trophoblast differentiates into:
  1. An inner cytotrophoblast surrounding the blasocyst
  2. An outer layer of proliferating cells at the embryonic pole that lose their membranes to form the syncitiotrophoblast.
• The embryo becomes completely implanted in the endometrium by day 9, via the action of hydrolytic enzymes from the cytotrophoblast.

• A small region of endometrium where the blastocyst implanted is filled in by material called the coagulation plug.

• By day 8, the embryoblast splits into 2 layers:
  1. The epiblast (primitive ectoderm)
  2. The hypoblast (primitive endoderm), thus forming the bilaminar germ disc.
• Within the epiblast, the amniotic cavity develops on day 8, with its fluid displacing some epiblast cells towards the embryonic pole that will become amnioblasts of the amniotic membrane.
• On day 8, cells at the periphery of the hypoblast migrate over the inner surface of the cytotrophoblast, forming a thin layer of extraembryonic endoderm called Heuser’s membrane, with the blasocyst cavity henceforth called the primary yolk sac.

• Extraembryonic reticulum is then secreted between the Heuser’s membrane and the cytotrophoblast, beginning the formation of the chorionic cavity.
• The developing chorionic cavity comes to be lined by extraembryonic mesoderm, whose origin is uncertain, although it will eventually envelop not only the yolk sac but the amnion as well, whilst the extraembryonic reticulum breaks down into fluid.

• On day 12, a new wave of hypoblast cells proliferate and migrate outwards, displacing the primary yolk sac towards the abembryoinc pole, before it disintegrates into exocoelomic vesicles that will themselves degenerate, leaving the new definitive yolk sac as a result.

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The Third Week

• On day 15, the primitive streak develops along the caudal midline of the germ disc, consisting of the primitive groove extending half way along the embryo, ending in the primitive pit at its cranial end, surrounded by the primitive node.
• This establishes the longitudinal axis of the embryo and bilateral symmetry in the future adult.

• On day 16, gastrulation commences with epiblast cells near the primitive streak developing pseudopodia that allow them to migrate through the primitive groove into the underlying space between the epiblast and hypoblast.
• The first wave of ingressing epiblast cells invades the hypoblast layer, eventually completely replacing it with a new layer of cells that becomes the definitive endoderm.
• Another wave of involuting cells fills the space between the epiblast and the definitive endoderm, forming the intraembryonic mesoderm.
• Once these two layers are formed, the epiblast is henceforth known as the ectoderm, and thus the 3 definitive layers of the trilaminar germ disc are all derived from the epiblast.

• As gastrulation proceeds, the primitive streak retreats caudally, giving rise to a midline mass of mesoderm called the caudal eminence on day 20, and disappearing by day 26.
• The ingressing mesoderm differentiates according to its position along the primitive streak (ie. its site of origin), as cells that migrate through the primitive pit come to lie in the midline, firstly forming a prechordal plate of compact mesoderm, followed by the hollow tube of the notochordal process.

• The notochordal process grows cranially as the primitive streak retreats, becoming complete by day 20, and then begins to transform into a solid rod.
• First it fuses with the endoderm, then it opens ventrally from the region of the primitive pit, flattening to form the notochordal plate and just transiently forming the neurenteric canal between the yolk sac and the amniotic cavity.
• At days 22-24, the notochordal plate detaches from the endoderm back into the mesoderm space, becoming a solid rod called the notochord.

• Meanwhile, by day 19, 2 depressions in the ectoderm have fused with underlying endoderm to form bilaminar membranes:
  1. The buccopharyngeal membrane at the cranial end
  2. The cloacal membrane at the caudal end

• By day 17, the mesoderm cells that migrated lateral to the primitive streak begin to condense into:
  1. The cylindrical paraxial mesoderm adjacent to the notochordal process
  2. The less pronounced intermediate mesoderm lateral to the paraxial mesoderm
  3. A flattened sheet of lateral plate mesoderm most laterally
• This process occurs craniocaudally, and the lateral plate mesoderm then splits into a further 2 layers:
  1. A ventral layer next to the endoderm called the splanchnopleuric mesoderm
  2. A dorsal layer next to the ectoderm called the somatopleuric mesoderm.

• As the paraxial mesoderm forms, it becomes faintly segmented into rounded somitomeres, with several pairs developing firstly in the cranial region, then cervical, thoracic, lumbar, sacral and coccygeal regions.
• The somitomeres become further segmented into somites, except for the first 7 pairs, with the first somites appearing on day 20, and with the process completed by day 30, with a final count of about 37 pairs starting from the occipital region to the embryonic tail.
• The somites establish the segmental organisation of the body, with the first 4 pairs contributing to the skull; the next 8 pairs contributing to the cervical region; the next 12 pairs being thoracic somites; the next 5 pairs being lumbar somites; followed by 5 sacral, and finally 3 coccygeal somites.

• The neural plate also begins to develop at day 18, with the epiblast cranial to the primitive pit thickening in response to inducing substances secreted by the underlying prechordal and notochordal plates, becoming columnar, pseudostratified neuroepithelial cells (neuroectoderm).

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The Fourth Week

• The somites develop a central cavity polulated by core cells, before rupturing on their medial sides, forming:
  1. The sclerotome medially, that surrounds the developing notocord and neural tube
  2. The dermomyotome that is displaced laterally, and will itself split into:
     1. A dermotome
     2. A myotome
• The sclerotome surrounding the notochord ventrally will develop into vertebral bodies, whilst the dorsal portion surrounding the developing neural tube will form vertebral arches, under the influence of inducing substances.
• Abnormal induction of the sclerotomes and neural tube causes spinal defects such as scoliosis from the vertebral body rudiments, or spina bifida from the vertebral arch rudiments.

• Each sclerotome then splits into cranial and caudal segments, with spinal segmental nerves emerging between this split, and the vertebrae are formed from the fusion of the caudal half of each sclerotome with the cranial half of the next, with the cranial half of the 1^st sclerotome fusing with the occipital bone.
• The intervertebral discs then form from the sclerotomes, with their nucleus pulposus core derived from notochord cells.
• Cartilagenous ribs develop from costal processes on thoracic vertebrae, and by day 45, the first 7 will join with the sternum that developed from 2 ventral sternal bars.

• The dermotome cells migrate to the surface ectoderm of the corresponding segmental region to  form the dermis, although most of the dermis is derived from somatopleuric lateral plate mesoderm.
• The myotome develops into myogenic cells, splitting to form:
  1. A dorsal epimere, that will form the deep muscles of the back
  2. A ventral hypomere that will form the anterolateral thoracic and abdominal wall muscles
• Myoblasts also invade the limb buds for limb musculature.

• Meanwhile, the cephalic end of the embryo begins folding ventrally on day 22, giving rise to the mesencephalic flexure that divides the prosencephalon (forebrain) cranially and rhombencephalon (hindbrain) caudally.
• The rhombencephalon becomes faintly segmented into rhombomeres, whilst the narrow caudal portion of the neural plate (the future spinal cord) lengthens rapidly.

• Neurulation, the folding of the neural plate into the neural tube, commences with the neural groove acting as a hinge for the 2 neural folds as they rotate around so that their lateral lips fuse dorsally, enclosing the neural canal, whilst simultaneously detaching from the overlying surface ectoderm as it fuses as well, and sinking into the posterior body wall.
• There may be several points of fusion, initially in the occipital area before the canal is continuous, leaving open the cranial and caudal neuropores that will close on days 24 and 26, respectively.
• Formation of the neural tube caudal to somite 31 occurs by secondary neurulation, where a solid neural cord derived from the caudal eminence cavitates to join the lumen of the neural canal, and is complete by week 8.

• Neural crest cells that originated in the lateral lips of the neural folds detach in a craniocaudal wave from day 22, migrating to many different parts of the body, for differentiation into a variety of structures.

• The ventricular layer of cells surrounding the neural canal proliferates to produce most of the cell types of the future central nervous system.
• The 1^st wave of proliferation from this layer produces neuroblasts (future neurons) that migrate peripherally to form an outer mantle layer (the future grey matter of the CNS), which in turn gives rise to another peripheral layer: the marginal layer (the future white matter of the CNS).

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