Embryonic Development in Humans: Gametogenesis, Fertilization, Gastrulation and Organogenesis

Epigenesis vs. preformationism: Aristotle and William Harvey proposed epigenesis, the view that the embryo develops progressively from an undifferentiated, homogeneous mass. Malpighi and other preformationists maintained that a fully formed miniature organism, the homunculus, already existed in the gamete.

Gametogenesis

Spermatogenesis: spermatogonium (mitosis) → primary spermatocyte → meiosis I → secondary spermatocyte → meiosis II → spermatids → spermatozoa (spermiogenesis).

Oogenesis: oogonium (mitosis) → primary oocyte (arrested for a long period) → primordial follicle (puberty, rapid growth) → primary follicle → zona pellucida → secondary follicle → tertiary follicle (Graafian follicle) → second meiotic division (arrested at metaphase II) → corpus luteum (corpus rubrum, corpus luteum) → corpus albicans.

Types of Egg Yolk

The yolk contains phosvitin, lipovitellin and immunoglobulins.

• By amount of yolk: alecithal, oligolecithal, mesolecithal, macrolecithal.
• By distribution: isolecithal (homogeneous) and anisolecithal (yolk displaced toward the centre or the vegetal pole, telolecithal).

Sperm Capacitation

Capacitation involves β-amylase, which disperses the corona radiata; the Sp56–ZP3 interaction; K⁺ channels; and phosphorylation of acrosin.

Penetration and Fertilization

The acrosome releases lysin, acrosin and phospholipase A, allowing the sperm to penetrate the zona pellucida by binding ZP2 and integrin. Binding of the sperm to CD9 forms the cone of fertilization. A Ca²⁺ channel opens and pH changes trigger the release of cortical granules, which produces the block to polyspermy. The fusion of the pronuclei constitutes amphimixis.

Increased permeability: sperm entry activates G protein, phospholipase C, and PIP₂ hydrolysis into IP₃ and diacylglycerol, which activates the Na⁺/H⁺ pump and alters pH.

Hydatidiform mole: a tumour resulting from a compensatory paternal (sperm-derived) contribution.

Cleavage

The zygote divides into totipotent blastomeres.

• Holoblastic cleavage (complete; isolecithal eggs) and meroblastic cleavage (incomplete; anisolecithal eggs).
• Radial cleavage (amphioxus and echinoderms): meridional, equatorial, and descentral meridional-equatorial patterns.
• Rotational cleavage (mammals): asynchronous, slow, compacted; resulting in external cells (trophoblast, specified by Cdx2) and internal cells (totipotent, expressing Oct4 and Foxd3).
• Discoidal cleavage (birds): occurs in the blastodisc, forming a subgerminal cavity.

Gastrulation

• Birds: invagination through the primitive streak (ZMP) and a subgerminal cavity.
• Mammals: formation of the hypoblast by delamination and the epiblast.

Germ Layers

• Mesoderm: cephalic mesoderm, notochord, somites, lateral plate, dermis, blood vessels.
• Endoderm: digestive and respiratory tracts, larynx.
• Ectoderm: epidermis, central nervous system, neural crest.

Body Axes

In birds:

• Dorsal–ventral: basic (alkaline) versus acidic, yolk, positive; ventral; posterior (ZMP) and gravity.
• Left–right: Shh, Caronte, BMP, Nodal, Leftyy, Pitx2 (right side); Activin, Fgf8, Caronte, BMP, Snail (left side).

In mammals: cranial–caudal axis controlled by Hox genes a, b; dorsal–ventral axis by sperm entry point and animal pole; left–right asymmetry by villous movement, dynein, Fgf8, Nodal and Lefty.

Irreversibility: from the moment of determination, separation of the tube and neural plate occurs: E-cadherins are expressed in the ectoderm and N-cadherins in the neural plate.

Neural Tube Patterning

• Dorsal: surface ectoderm produces TGF-β, which induces dorsolateral hinge points; BMP4 specifies sensory neurons.
• Ventral: notochord produces Shh, which induces the medial hinge point; motor neurons and floor plate form.

Neural Tube Defects and Related Malformations

• Spina bifida (rachischisis): failure of neural tube closure at cephalic and medullary levels.
• Myeloplasia: malformation of the spinal cord.
• Hydrocephalus: accumulation of cerebrospinal fluid (CSF).

Skin Development

The epidermis consists of a basal layer and a spinous layer (stratum of Malpighi).

• Regulation: TGF-α acts in an autocrine manner on basal cells; excess TGF-α contributes to psoriasis. KGF acts in a paracrine manner, produced by fibroblasts, stimulating basal cells.
• The primordial follicle (hair follicle) expresses β-catenin, which induces the dermal papilla.
• Epidermal thickenings: the bulge contains stem cells and melanocytes; sebaceous glands produce sebum.