HUMAN EMBRYOLOGY (First eight weeks of early human development) Recommended reading: Keith Moore, Vid Persaud The developing human: Clinically oriented embryology. 8th ed. Elsevier, 2008: 1-91, 110-143

Progenesis – includes formation of spermatozoa and oocytes - male and female germ cells Spermatogenesis – spermatozoa development - is maintained in the seminiferous tubules of testes Oogenesis – oocyte production - is maintained within the ovarian follicles

MORPHOLOGY OF SPERMATOZOON AND OOCYTE

FERTILIZATION Fusion of a spermatozoon with oocyte resulting in formation of one-cell embryo – zygote Fertilization in most of the cases occurs within the ampullary region of the uterine tube on days 14-15 of ovarian-menstrual cycle (after the ovulation – oocyte release from the ovary) and insemination with sperm Fertilization is accounted as the first day of embryogenesis

MAIN EVENTS DURING FERTILIZATION Capacitation Acrosomal reaction Penetration of corona radiata and zona pellucida Fusion of the oocyte and sperm cell membranes Cortical and zona pellucida reactions Resumption of 2nd meiotic division Metabolic activation of the egg Restoration of diploid number of chromosomes

Fertilization

The main results of fertilization: Restoration of the diploid number of chromosomes Determination of the sex of embryo Initiation of a cleavage

CLEAVAGE of the zygote (first week of development) Zygote → blastomeres → 8-cell stage (compaction) →16-cell stage (morula, or mullberry) → blastocyst ↓ inner cell mass → embryoblast outer cell mass → trophoblast Cleavage means enlargement of total cell number with simultaneous reduction of their size resulting from the abbreviated mitotic cycle

Cleavage of the zygote and formation of the blastocyst

Summary of the ovarian cycle, fertilization and human development during the first week

IMPLANTATION Adhesion – attachment of blastocyst to the surface of endometrium – day 5 Invasion – introduction of blastocyst inside the uterine wall resulting from its lytic digestion – days 6-12 Uteroplacental circulation – starts day 10, when maternal blood from eroded uterine vessels provide nutritional support to the developing embryo

Early stages of implantation: A – 6 days – blasocyst attachment; B – 7 days – invading blastocyst

BILAMINAR EMBRYONIC DISC FORMATION: SECOND WEEK OF DEVELOPMENT Embryoblast differentiates into bilaminar embryonic disc: Epiblast Hypoblast (local thickening of which forms prechordal plate, indicating future cranial region of the embryo) Trophoblast differentiates into: Cytotrophoblast Syncytiotrophoblast, which erodes blood vessels of endometrium and establish haematotrophic circulation Cavities formation: Amniotic cavity Umbilical vesicle (yolk sac)

Implanted blastocysts: A – 10 days; B – 12 days

End of the second week (day 14): formation of chorionic sac and chorionic villi

THIRD WEEK OF DEVELOPMENT: GASTRULATION – formation three of germ layers Formation of the primitive streak with primitive node and primitive pit Migration of cells from epiblast Epiblast gives birth to three primary tissues: - ectoderm - mesoderm - endoderm Resulting from cellular migration and cavities formation embryo is becoming three laminar, surrounded with two cavities – umbilical vesicle (yolk sac) and amniotic cavity

Origin of embryonic tissues

Dorsal view of a 16-day embryo

Third week: further events Notochord formation Development of somites (each of it including dermatome, sclerotome and myotome) Neural tube and neural crest formation (neurulation) Development of primordial cardiovascular system Development of intraembryonic coelom Development of secondary and tertiary chorionic villi

18 day: formation of notochord and neural groove

Embryos of days 19 to 21: formation of somites

Embryonic days 19-21: neurulation

Day 21: primordial cardiovascular system and tertiary chorionic villi

Organogenesis: fourth to eight weeks During the fourth week a flat trilaminar embryonic disc is folding with the formation of a cylindrical shape embryo Folding of the ends of the embryo in the median plane results in formation of cranial and caudal regions moving ventrally as the embryo elongates Folding of the embryo in the horizontal plane produces right and left lateral folds

Folding of embryos during days 21-22-26-28

Derivatives of three germ layers: endoderm, ectoderm and mesoderm

ENDODERMAL GERM LAYER DERIVATIVES Epithelial lining of - gastrointestinal tract - respiratory tract - urinary bladder Parenchyma of - thyroid, parathyroid glands - liver and pancreas Epithelial lining of the tympanic cavity and auditory tube

ECTODERMAL GERM LAYER DERIVATIVES: central nervous system peripheral nervous system sensory epithelium of ear, nose and eye epidermis (including hair and nails) pituitary, mammary and sweat glands oral cavity mucosa, enamel of the teeth

MESODERMAL GERM LAYER DERIVATES splanchnic, or visceral mesoderm layer intermediate mesoderm somatic, or parietal mesoderm layer dorsal mesoderm, which forms somites Each somit consists of three components: - sclerotome - dermatome - myotome

Human embryo 28 days with somites

Number of somites correlated to approximate age in days Approximate age No. of somites (days) 20 1-4 21 4-7 22 7-10 23 10-13 24 13-17 25 17-20 26 20-23 27 23-26 28 26-29 30 34-35

EXTRAEMBRYONIC ORGANS Placenta - embryonic part – chorionic membrane (transformed trophoblast of the blastocyst) - maternal part – decidual membrane (pregnancy-transformed functional layer of endometrium) Umbilical cord (formerly connecting stalk) Umbilical vesicle (yolk sac) Allantois Amnion

Sagittal section through gravid uterus at 4 weeks

56 days old embryo with fetal membranes