Lecture 11 Human Development

• Human development encompasses fertilization through fetal development.
• Key objectives involve identifying stages, recognizing abnormalities, teratogens, and congenital anomalies in human embryonic development

Stages of Human Development

• Fertilization marks the first stage.
• Blastocyst development and implantation follow fertilization.
• Embryologic development is the third stage.
• Fetal development is the final stage.

Fertilization (Day 0)

• Gametes, sperm, and ova, contain 23 chromosomes each.
• The father's sperm determines the sex of the offspring.

Potential Problems with Fertilization and Implantation

• Fertilization failure can occur.
• Defective sperm capacitation and acrosomal reaction
• Fallopian tubal blockage
• A ripened egg might not be released through ovulation.
• Polycystic Ovarian Syndrome and insulin resistance can cause errors.
• Fallopian tube stricture secondary to salpingitis.
• Sperm dysmotility
• Altered Oviductal Environment from growth factors, hormones, proteases, antioxidants, glycosidases, proteoglycans, cytokines, and glycoproteins.
• Implantation failure can occur
• Altered uterine secretions could happen.
• Defective endometrium receptivity.
• Altered adhesion between selectins, integrins, cadherins, trophinin, and heparin-binding epidermal growth factor (HB-EGF)
• Various conditions or issues that can occur include uterine causes, systemic causes, rejection, problems with the maternal body or the embryo itself.

Blastocyst Development & Implantation.

• Fast cell division happens, Zygote converts to Morula then a Blastocyst
• Implantation occurs between days 6 and 10.
• HCG secretion starts around the time of implantation.
• The blastocyst attaches to the uterine wall on day six.

Early embryologic Development.

• Occurs between weeks 2-8
• There are primary germ layers by week 3:
  • Ectoderm
  • Mesoderm
  • Endoderm

Weeks 2 to 8 Embryo Development

• Organogenesis begins

Ectoderm derivatives include:

• Neural crest
• Nerves, Schwann cells
• Neural tube
• Brain, spinal cord
• Surface ectoderm
• Epidermis

Mesoderm Derivatives

• Muscles
• Bones
• Connective tissue
• Heart
• Urogenital System

Endoderm Derivatives

• Gut tube
• Liver
• Pancreas
• Lungs
• Thymus
• Parathyroid

Potential Problems of the Embryo

• Age
• 4 weeks with a neural tube defect
• Heart can have issues.
• Limbs can develop defect.

Fetal Development includes

• Weeks 9-38
• The period is critical for functional defects, but less sensitive for major congenital anomalies compared to later stages.

Effects of Teratogens on Fetal Development

• Major congenital anomalies are most likely to occur during the embryonic period.
• Functional defects and minor anomalies are more common during the fetal stage.
• Neural tube defects, truncus arteriosus, atrial septal defect, mental retardation indicate neural tube defects

Teratogens

• Any agent that causes an abnormality following fetal exposure
• Commonly discovered after an increased prevalence of a particular birth defect.
• Examples include infectious agents, medications, recreational drugs, physical agents (like radiation or hyperthermia), maternal health factors (like diabetes), and environmental chemicals.

Infectious TORCH agents include

• Toxoplasma gondii
• Others: HIV, Hepatitis, Syphilis, Varicella-Zoster, Parvovirus
• Rubella
• Cytomegalovirus
• Herpes simplex virus
• During the embryologic state, TORCH infections can cause growth restriction, mental retardation, cataracts, and congenital cardiac anomalies.
• In the fetal stage, tissue injury is the main result, leading to encephalitis, chorioretinitis, hepatosplenomegaly, pneumonia, and myocarditis.

Common Symptoms of TORCH Infections include

• Hepatosplenomegaly, fever, poor feeding, growth retardation, jaundice, thrombocytopenia, hearing impairment, developmental delay, autism, and potentially death.

Substances - Legal and Illegal

• ACE inhibitors: Can cause renal failure, oligohydramnios, hypocalvaria.
• Alkylating agents: Can cause multiple anomalies, such as ear/facial abnormalities or absence of digits.
• Aminoglycosides: Can cause Ototoxicity.
• Antiepileptic drugs: Can cause neural tube defects, cardiac defects, cleft palate, and skeletal abnormalities.
• Diethylstilbestrol: Can cause vaginal clear cell adenocarcinoma and congenital Müllerian anomalies.
• Fluoroquinolones: Can cause Cartilage damage
• Folate antagonists: Can cause neural tube defects
• Isotretinoin: Can cause Craniofacial defects.
• Lithium: Can Ebstein anomaly
• Methimazole: Can cause Aplasia cutis congenita .
• Tetracyclines: Can cause discolored teeth and inhibited bone growth.
• Thalidomide: Can cause Limb defects.
• Warfarin: Can cause bone and cartilage deformities, optic nerve atrophy, and cerebral hemorrhage.
• Substance use-Alchohol: Fetal alcohol syndrome.
• Cocaine: Can cause Preterm birth, low birth weight, and fetal growth restriction .
• Tobacco Smoking: Can cause Preterm birth, low birth weight, FGR, sudden infant death syndrome , and ADHD.

Errors in Morphogenesis

• Agenesis: Absent organ due to absent primordial tissue.
• Aplasia: Absent organ despite presence of primordial tissue.
• Hypoplasia: Incomplete organ development, primordial tissue present.
• Disruption: Secondary breakdown of tissue with normal developmental potential
• Deformation: Extrinsic mechanical distortion (e.g., congenital torticollis) during the fetal period.
• Malformation: Intrinsic developmental defect (e.g., cleft lip/palate) during the embryonic period.
• Sequence: Abnormalities result from a single primary embryologic event (e.g., oligohydramnios Potter sequence).
• Field defect: Disturbance of tissues that develop in a contiguous physical space.
• Malformations result from intrinsically abnormal development, with severity ranging from incidental to lethal, e.g., cleft lip/palate
• Disruptions result from secondary destruction of previously normal organs or body regions due to environmental agents, e.g., amniotic bands.
• Deformations represent extrinsic disturbance of development due to localized or generalized compression of the growing fetus, e.g., congenital arthrogryposis
• Sequence - One or more secondary morphologic anomalies known or presumed to cascade from single malformation
• Syndrome - Recognizable pattern of congenital anomalies that are know or thought to be casually related

Potter Sequence

• Begins with oligohydramnios, leading to fetal growth restriction and organ hypoplasia.

Neural Tube Defects

• Occurs when the caudal neuro is not closed.

Neural Tube Defects (cranial end)

• Encephalocele: A portion of the brain protrudes through a gap in the skull
• Anencephaly: Cranial part of the neural tube fails to close during fetal development.

Neural Tube Defects (caudal end)

• SpIna bifida is the most common NTD failure of the neural tube.
• Associated with folate deficiency.
• It can be prevented with adjust Rx and supplement! -Types of Spina bifida
• Sacral dimple or tuft of hair is Occulta which is less common:
• Meningocele most serious type covering of the spinal cord
• In the spinal cord enclosed in the cyst the called more more type myelomeningocele