Embryology

PRELIMINARY REMINDERS: Mitosis and Meiosis

CHAPTER 1: The meeting of the spermatozoon and the oocyte

1.Ovulation (reminders)

 1.1. The female genital tract

 1.2. The ovary and primary oocytes in prophase I (dictyate stage)

 1.3. Follicular stages

 1.4. The ovarian cycle (hypothalamo-pituitary hormonal control and ovarian hormonal feedback)

 1.5. Maturation of the oocyte and oocyte cytoplasm in the dominant follicle shortly before ovulation: from the primary oocyte in prophase I to the secondary oocyte in metaphase II

 1.6. Ovulation and the interception of the secondary oocyte by the oviduct

2.The long journey of spermatozoa

 2.1. The male genital tract (reminder)

 2.2. Spermatogenesis (reminder)

 2.3. Maturation of spermatozoa and their journey through the male genital tract and then the female genital tract

2.3.1. Journey of the spermatozoa in the male genital tract

2.3.2. Ejaculation

– composition of semen

– semen analysis (spermogram)

2.3.3. Journey of the spermatozoa in the female genital tract

– pathway of spermatozoa

– capacitation

3.Fertilization: Interaction between Spermatozoon and Oocyte

 3.1. Penetration of the corona radiata cells

 3.2. Contact with the zona pellucida

 3.3. The acrosome reaction and traversal of the zona pellucida

 3.4. Attachment and fusion of gamete plasma membranes

 3.5. Prevention of polyspermy

 3.6. Penetration of the spermatozoon into the oocyte (impregnation)

 3.7. Completion of the second maturation division of the secondary oocyte and extrusion of the second polar body

 3.8. Formation of the paternal and maternal pronuclei

 3.9. Formation of the zygote

 3.10. Appendix: selection of the sex of the child to be conceived

CHAPTER 2: Segmentation and Implantation

1.Segmentation

 1.1. Mitosis and morula formation

 1.2. Formation of the blastocyst

 1.3. Blastocyst hatching

 1.4. Migration of the embryo along the oviducts

2.Implantation

 2.1. The endometrium

 2.2. Apposition and adhesion of the blastocyst to the uterine mucosa

 2.3. Invasion of the trophoblast or embedding

 2.4. Implantation anomalies

– Ectopic pregnancy

– Placenta praevia

3.Considerations regarding the first week of embryonic development

 3.1. Embryonic fasting

 3.2. The role of mitochondria

 3.3. The embryo is a tolerated allogeneic graft

 3.4. Genomic imprinting: functional non-equivalence of male and female pronuclei

4.Contraceptive methods

 4.1. Mechanical (barrier) contraception

 4.2. Chemical contraception

 4.3. Hormonal contraception

 4.4. Contragestion

 4.5. Sterilization

 4.6. Future prospects

5.Treatment of infertility by in vitro fertilization and embryo transfer

 5.1. Historical background

 5.2. Indications

 5.3. Technical aspects

– Oocyte production stimulation

– Collection of gametes (secondary oocytes and spermatozoa)

– In vitro fertilization and embryo culture

– Embryo transfer

– Preservation of surplus embryos

 5.4. Variants

– Artificial insemination

– Intratubal transfer of gametes

– Surrogate mothers

– SuZI (SUbZonal Injection)

– ICSI

– Cytoplasm transfer

 5.5. Risks associated with assisted reproductive technology (ART)

– Increased risk of malformations?

– Risk of disruption of the parental imprinting process?

6.Use of embryos for research purposes: stem cells

 6.1. Definitions

– Totipotent stem cells

– Pluripotent stem cells

– Multipotent stem cells

– Unipotent stem cells

 6.2. Origin of stem cells

– Embryonic stem cells (ES)

– Fetal stem cells

– Adult stem cells and induced pluripotent stem cells (iPS)

 6.3. Applications and potential risks

CHAPTER 3: The embryonic disc

1.The bilaminar embryonic disc (2nd week)

2.The trilaminar embryonic disc (3rd week)

 2.1. Gastrulation

 2.2. Neurulation

 2.3. Mesoderm differentiation

3.General considerations after 4 weeks

 3.1. Embryonic delimitations

– Anterior and posterior delimitation of the embryo

– Lateral delimitation of the embryo

– The umbilical ring

 3.2. Fate of the 3 embryonic layers

CHAPTER 4: Decidua, fetal membranes and placenta

1.Decidua and fetal membranes

 1.1. Definitions

 1.2. Relationship of fetal membranes and decidua at the second month of gestation

 1.3. Relationship of fetal membranes and decidua at the fourth month of gestation

2.The placenta

 2.1. The placenta during the first two weeks of gestation

 2.2. The placenta from 2 to 12 weeks of gestation

 2.3. The placenta after 12 weeks of gestation

 2.4. Cross-sections of placental villi according to gestational age

3.Twins

 3.1. Biovular twins

 3.2. Uniovular twins

CHAPTER 5: Molecular aspects of embryogenesis

Introduction

1.Architect genes or homeotic genes (transcription factors)

 1.1. The homeodomain protein family (Hox type)

 1.2. The zinc finger protein family

 1.3. The basic helix-loop-helix (bHLH) protein family

 1.4. The paired box (Pax) protein family

 1.5. Other families (POU, Winged helix, ...)

2.Mechanisms of regulation of effector gene and pro-apoptotic gene expression

 2.1. The promoter

 2.2. Enhancers and silencers

 2.3. Post-transcriptional regulation: alternative intron splicing

 2.4. Post-transcriptional modifications

3.The induction process

 3.1. Principle and definitions

 3.2. Paracrine and juxtacrine intercellular interactions

 3.3. Paracrine signalling molecules (growth and differentiation factors)

– Fibroblast growth factors (FGFs)

– Transforming growth factors beta (TGFβ)

– Hedgehog proteins

– Wingledd related proteins (WNT)

4.Embryo patterning

5.Illustrative examples

 5.1. Eye formation

 5.2. Limb formation

CHAPTER 6: Organogenesis

1.The various stages of embryonic development

2.Formation of the heart and cardiovascular system

 2.1. Cardiac looping

 2.2. Primitive atrial septation

 2.3. Primitive ventricular septation

 2.4. Embryonic blood circulation

2.4.1. Arterial network

– Fusion of the dorsal aortas

– Evolution of the aortic arches

– Branches of the dorsal aorta

– Umbilical arteries

2.4.2. Venous network

– Superior vena cava

– Inferior vena cava

– Portal vein

 2.5. Comparison of circulation before and after birth

 2.6. Cardiac malformations

– Generalities

– Interatrial communications

– Common atrioventricular canal

– Interventricular communications

– Tricuspid atresias

– Common arterial trunk

– Aortic atresia

– Tetralogy of Fallot

– Aortic coarctation

– Dysphagia lusoria

3.Formation of the respiratory system

 3.1. Lung development

– Embryonic stage

– Pseudoglandular stage

– Canalicular stage

– Saccular stage

– Alveolar stage

 3.2. Diaphragm closure

 3.3. Pulmonary development anomalies

– Pulmonary agenesis or hypoplasia

– Laryngotracheal fistulas

– Alveolocapillary dysplasia

– Respiratory distress syndrome due to surfactant deficiency

– Congenital pulmonary cysts

4.Formation of the urogenital system

 4.1. Renal system formation

4.1.1. Nephrogenic cord development

– The pronephros

– The mesonephros

– The metanephros

4.1.2. Congenital renal anomalies

 4.2. Genital system formation

4.2.1. Germ cells

4.2.2. Undifferentiated gonads

4.2.3. Differentiated gonads

– Testicular differentiation and male genital tracts

– Ovarian differentiation and female genital tracts

 4.3. Cloaca septation

 4.4. Urogenital sinus differentiation

 4.5. External genital organs

 4.6. Urogenital system anomalies

4.6.1. Testicular migration anomalies

4.6.2. Uterine anomalies

4.6.3. Cloaca septation anomalies

4.6.4. Penile urethra closure anomalies

 4.7. Biology of sexual differentiation

4.7.1. Normal sexual differentiation

– Primary gonadal differentiation

– Testicular determination

– Ovarian determination

– Differentiation of male genital organs

– Differentiation of female genital organs

4.7.2. Sexual ambiguities

– True hermaphroditism

– Male pseudohermaphroditism and "female XY"

– Female pseudohermaphroditism and "male XX"

– Overview table

5.Formation of the digestive tract and its appendages

 5.1. Introduction

 5.2. Differentiation of the foregut

– Pharyngeal segment

– Thoracic segment (esophagus)

– Abdominal segment (stomach, duodenum, liver, pancreas)

 5.3. Differentiation of the midgut

 5.4. Differentiation of the hindgut

 5.5. Anomalies of digestive tract formation and appendages

5.5.1. Foregut pathologies

– Branchial cyst/fistula, thyroglossal duct cyst

– Esophageal atresia/stenosis, tracheoesophageal fistula

– Pyloric stenosis

– Duodenal stenosis/atresia

– Biliary atresia

– Annular pancreas

5.5.2. Midgut pathologies

– Meckel’s diverticulum

– Omphalocele

– Umbilical hernia

– Malrotation

– Small intestine stenosis/atresia

– Aganglionic megacolon (Hirschsprung’s disease)

5.5.3. Hindgut pathologies

– Anal imperforation, anal atresia, fistula

6.Formation of the osteoarticular system

 6.1. Development of somites

 6.2. Formation of the vertebral column

 6.3. Formation of the limbs

7.Formation of the face and neck

 7.1. Formation of the facial massif

 7.2. Septation of the stomadaeum

 7.3. Facial development anomalies

 7.4. Branchial arches

– Ectodermal aspect

– Endodermal aspect

 7.5. Formation of the tongue

 7.6. Formation of the thyroid

8.Formation of the nervous system

 8.1. Formation of the neural tube

 8.2. Formation of the cerebral vesicles

 8.3. Formation of the spinal cord

 8.4. Formation of the pituitary gland

 8.5. Formation of the sensory organs

– Eye formation

– Ear formation

CHAPTER 7: Reproductive and Embryogenesis Anomalies

1.Introduction

2.Early miscarriages

 2.1. Meiotic nondisjunctions

 2.2. Inherited chromosomal imbalances

3.Congenital malformations

 3.1. Classification of congenital malformations

 3.2. Etiology of congenital malformations

3.2.1. Genetic factors

3.2.2. Infectious factors

3.2.3. Physical agents

3.2.4. Chemical agents

3.2.5. Hormonal or maternal factors

 3.3. Prevention of congenital malformations

 3.4. Screening of congenital malformations and prenatal diagnosis

3.4.1. Non-invasive methods

– Immunological monitoring

– Hormonal screening

– Imaging-based screening

– Non-invasive prenatal screening (NIPT: non invasive prenatal testing)

3.4.2. Invasive methods

– Amniocentesis or amniotic fluid sampling

– Chorionic villus sampling (CVS)

– Cordocentesis or umbilical cord sampling

– Fetoscopy

3.4.3. Non-invasive prenatal diagnosis

– Circulating trophoblastic cells

– Circulating fetal DNA (cffDNA: cell-free fetal DNA)

– Circulating fetal RNA (cffRNA: cell-free fetal RNA)

3.4.4. Preimplantation diagnosis

3.4.5. Preconceptional “diagnosis”

 3.5. Prenatal therapy