Human Life Cycle

Suzie Rayner





Human Life Cycle 1 – Is sex necessary? [Largely

covered in Endo]

 Describe the cardiovascular events associated with the erection of the penis.



Pudendal artery supplies blood to the penis.

Dorsal vein removes blood from the penis.



Erection occurs from increased blood flow to the corpora cavernosa. This is stimulates by

parasympathetic nervous system which induces dilation of pudendal artery.



Outflow of blood is stopped by compression of the dorsal vein due to increase in pressure

in corpora cavernosa.



[Urethra is protected by corpus spongiosum which is less turgid]









 List the neural control mechanisms involved in penile erection, indicating

which one is the most important



Most important is parasympathetic nervous system as increased parasympathetic

action to the smooth muscle of the pudendal artery induces dilation → increased blood

flow in corpora cavernosa.



[Parasympathetic nervous system counteracts the sympathetic maintained myogenic

tone.]



Afferent pathway:



Tactile stimulus → afferent fibres in pudendal nerve → spinal cord



Efferent pathway:

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3 possible:



Nervous System Parasympathetic Somatic Sympathetic

Nerve Pelvic Pudendal Hypogastric

Erection? Promotes Promotes Depresses



Penis: Flaccidity → Tumescence → Erection









Mechanism of smooth muscle dilatation



[Release of acetylcholine stimulates NO synthase → NO gets converted to cGMP which

causes dilatation of arterial smooth muscle.]









Clitoris is the erectile tissue in women, increases in size with increased blood flow.

Mechanism is likely to be due to release of NO.



 Define the various stages of the menstrual cycle

 Understand the changes that occur in the endometrium during the different

stages of the menstrual cycle

Suzie Rayner





Menstrual Phase:

 4-5 days

 Cycle begins on first day of menstruation

 Shed blood and endothelium

 Flow of 20-80ml



Proliferation Phase [N.B. everything becomes more]:

 9 days

 Growth of follicles occurs, controlled by 17β-oestradiol from follicles

 2-3x increase in thickness of endothelium

 [phase of repair and proliferation – epithelium repairs, glands increase in

number]



Secretory Phase:

 13 days

 Controlled by progesterone (luteal phase of ovarian cycle) and oestrogen (but

less so)

 Formation, functioning and growth of corpus luteum

 Glands in epithelium become wider and tortuous [due to progesterone]

 Thicker endometrium [due to progesterone and oestrogen]

 Spiral arteries



 Know how the different stages of the ovarian cycle relate to the stages of the

menstrual cycle

 Describe the various stages and events of the ovarian cycle and the hormones

acting at these various stages



Follicular phase and luteal phase of the ovarian cycle are linked by chemicals produced

during these phases, which changes in endometrium.



Follicular phase produces 17β-oestradiol → growth of follicle

Luteal phase produces progesterone → widening of glands and thickening of

endometrium



 Know which hormones act at various stages of the menstrual and ovarian cycle

Suzie Rayner









 Explain why the changes occurring in the endometrium are important for

implantation

 Describe how the endometrium is maintained if pregnancy ensues



Corpus Luteum is maintained by human chorionic gonadotrophin (hCG), which is

produced by the syncytiotrophoblast.



Therefore progesterone and oestrogen continue to be produced.



 Describe the endometrial changes if pregnancy does not occur



No fertilization

 Corpus luteum regresses

 Menstrual phase occurs

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 Understand that the menstrual cycle various in its length from female to female

and also within one female from month to month

 Describe other methods of how the sperm and egg can be artificially brought

together

In vitro fertilisation







Human Life Cycle 2 – In the beginning…



Summary of early development:



1st Trimester:

Weeks 1-2: Blastocyst stage

Weeks 3-8: Embryonic stage

Week 9 onwards: Fetal stage



2nd Trimester:

Rapid Growth of Fetus



3rd Trimester:

Fat production



Fertilisation:

 Occurs in the fallopian tube, at the distal end (ampulla)

 Sperm penetrates the several oocyte coats

 Zona pellucida prevents polyspermy and permits implantation at correct site

 Fertilisation causes oocyte to complete meiosis II – completes number of

chromosomes, determines gender



Post-fertilisation:

 Zygote travels down fallopian tubes

 Divides – first cleavage at around 20 hours → Morula (12-16 cells) →

blastocyst

 Zona pellucida is shed

 Implantation, hCG production.

Suzie Rayner









 Why do we study development?

o Know how structures develop

o How normality arises/how abnormality arises

o Positioning of adult structures

o Understand that several tissues form at same time, requiring same genes



 What structures are required for development of the human to ensue?



Female and male germ cells. [Spermatozoon, Oocyte]



 Define and understand the following terms:



Gametes: mature germ cells [male – spermatozoa, female – oocytes]



Fertilisation: the process in which the nucleus of a spermatozoon enters the oocyte and

fuses with the female pronucleus to produce a zygote.



Pronuclei: nucleus of mature germ cells, haploid



Zona pellucida: clear, acellular membrane that surrounds the oocyte protecting against

polyspermy (multiple sperms entering)



Haploid: 23 chromosomes in the cell, 22 autosomes and 1 sex chromosome.



Diploid: 46 chromosomes in the cell, pairs of autosomes and a pair of sex chromosomes.



Implantation: process in which the blastocyst imbeds in the endometrium.

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First cleavage division: first cytoplasmic division by meiosis, cell membrane infolds as

a deep furrow, dividing cell into 2.



Formation of morula: the zygote when it has 12-16 cells (just before it becomes a

blastocyst)



Formation of blastocyst: hollow ball of blastomeres, formed when fluid is pumped into

morula after its compaction.



Inner Cell Mass: a.k.a embryoblast. Contains blastomeres which form embryo.



Trophoblast: Outside region of blastocyst which invades the endometrium, forms the

placenta.



Embryo: tissues arising from the zygote which later contribute to fetus/child.



 Comprehend that development does not always go to plan and that

abnormalities can arise at different levels.

 Give examples of chromosomal abnormalities that may occur



Mosaicism, Structural, Numerical



Down’s syndrome (trisomy 21)

Turner’s syndrome (45, X)

Kleinefelter’s syndrome (47, XXY)

Patau’s syndrome (Trisomy 13)

Edward’s syndrome (Trisomy 18)



 Name possible sites where an ectopic pregnancy may arise.



Most common in the fallopian tubes (95%)

Other locations:

 Ovary

 Peritoneal cavity

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 Name the two layers that the inner cell mass differentiates into to give rise to

the bilaminar disk stage of development and how the two layers give rise to the

third body or germ layer of the embryo.



Inner cell mass differentiates into 2 layers:

 Epiblast – forms amniotic cavity and fluid

 Hypoblast – forms yolk sac









Day 15:



Gastrulation: formation of trilaminar embryo

 Coordinated process of cell movement.

 Has organiser at top and bottom end of embryonic ectoderm – Cranial and

Caudal

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 Primitive streak from caudal end – where cells from epiblast are proliferating

and moving into gap between epiblast and hypoblast.









This results in formation of 3 layers:

 Epiblast becomes ectoderm.

 The mesoderm forms between the two layers

 Hypoblast becomes endoderm.



 Primitive streak moves towards cranial end from caudal end

 Primitive node forms









Human Life Cycle 3 – Pattern Formation

 Name the structures that are derived from the three body or germ layers of the

embryo.



Ectoderm: develops into skin and nervous system

Mesoderm: develops into skeleton, muscle, kidney, heart, blood

Endoderm: develops into gut, liver and lungs



 Define how the neuroectoderm gives rise to the neural plate and how this

structure folds to form an early neural tube that will give rise to the brain and

spinal cord later in development.



Day 17:

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Notochord:

 forms at primitive node from invaginating epiblast cells

 extends cranially, forming basis of axial skeleton

 involved in inducing formation of neural tube and somite formation









Neurulation - Day 19-27:



 Notochord induces ectoderm to become

neuroectoderm.

 Neuroectoderm gives rise to:

o Neural plate

o Neural groove

o Neural folds

 Ultimately gives rise to neural tube



Neural Crest:

 arises from crest of neural folds

 migrates from neurectoderm into underlying

mesoderm [see following diagram]

 gives rise to:

o melanocytes (melanin production)

o Glial and Schwann cells

o cranial nerves

o odontoblasts (creation of dentin – tooth

enamel)

o connective tissue and bones of face and

skull

Suzie Rayner





 Define the divisions of the intra-embryonic mesoderm and briefly describe

which structures each will give rise to.



Intra-embryonic mesoderm is divided into:

 Paraxial mesoderm: becomes somites

 Intermediate mesoderm: becomes urogenital

 Lateral plate mesoderm: lines body cavities and surround organs (coelom) –

splits into two (visceral next to endoderm, parietal next to ectoderm)

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Somites [3 layers]:

 Sclerotome – precursor to cartilage and bone

 Myotome – precursor to muscle

 Dermatome – precursor to skin



1st – Day 20

Anterior to posterior, 35 by Day 30.

Parts of extra-embryonic mesoderm will become:

 Body stalk – umbilical cord

 Amnion, yolk sac, chorion









 Describe which two parts of the embryonic disk always remain as a bilaminar

disk and the consequences of this.



Buccopharangeal membrane at front of embryo and cloacal membrane at bottom.



These mark where the gut starts and finishes.



 Which part of the neural tube develops most vigorously during early

development and what is the consequence of this?

 Give an example of genetic regulation of embryonic development.



Example:

Hox genes:

 Establish A-P axis (anterior-posterior?)

 Differences in vertebrae

 CNS divisions

 Patterns of limbs



One signal that controls activation of Hox genes is Retanoic Acid (derivative of Vit. A)

Suzie Rayner







 Define the causes of abnormalities during embryonic patterning.



All Chromosomal

Genetic examples:

 Holt-Oram syndrome (heart/hand defects)

 Achondroplasia (dwarfism)

 Cleft lip

 CF



Environmental:

 Dietary

 Alcohol abuse

 Drug use

 Radiation

 Rubella



Spina Bifida (posterior neuropore doesn’t close properly, neural tissue bulges out)

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Summary of embryonic development (first 9 weeks)



Time Event Size

Day 6 Attachment to endometrial epithelium

Day 8-9 Implantation and formation of trophoblast

shell

Bilaminar embryonic disc

Day 12-13 Trophoblast invasion and contact with 2mm

maternal blood

Week 3 Formation of trilaminar disc 3mm

Formation of CNS

Formation of somites

Blood vessel initiation

Heart forms

Formation of placental villi

Week 4 Closure of neural tube 4mm

Face and arm initiated

Umbilical cord forms

Elaboration of placental villi

Week 5 Face and Limbs continue 5-8mm

Week 6 Face, ears, hands, feet, liver, bladder, gut, 10-14mm

pancreas

Week 7 Face, ears, fingers, toes 17-22mm

Week 8 Lungs, liver, Kidneys 28-30mm

Placental elaboration continues

Villous Localisation

Placental endocrinology becomes dominant



[N.B. up to Week 5, Week approximately equals Length]









HLC 4 – Body Cavities

Placental mammals evolved from egg-laying reptiles, therefore same cavities but newly

evolved roles:



Cavity/structure Role

Yolk sac Part in gut development, other than that redundant

Chorionic cavity Obliterated early

Chorion Gives rise to placenta

Amniotic cavity Embryo floats in it, later tests its urinary and respiratory

systems into it

Allantois Gives rise to part of urinary bladder

Allantoic mesoderm Gives rise to placental blood vessels

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Chorion and amnion

eventually fuse (chorio-

amnion) and obliterate

chorionic cavity.









[N.B. Amniocentesis – used to check for embryo abnormalities, culture embryonic cells

and test for α-fetoprotein as indicative of neural tube defect]



 Explain how the intra-embryonic coelom develops



 Cavities form in preoral and lateral plate mesoderm.

 These join to form a horseshoe shape called intra-embryonic coelom



The intra-embryonic coelom

develops into:



Pericardial cavity (cranially –

heart)



Pleural cavity (intermediate –

lungs)



Peritoneal cavity (caudally –

urogenital)

Suzie Rayner









 Explain how the cranial part of the intra-embryonic coelom forms the

pericardial cavity



Head and tail folding:

 Tucks developing heart and pericardial sac ventrally

 Pinches gut tube off yolk sac

 Narrows body stalk









Completion of head folding:

 Forebrain now cranial to heart

 Gut tube connected to yolk sac by narrow stalk

 Heart ventral to gut tube

 Original cranial part of coelom is now ventral to intermediate parts



 Describe the process of development of the visceral and parietal pericardium

 Explain the derivation of the visceral and parietal peritoneum



Develop from lateral plate mesoderm – splits in two:



 Visceral adjacent to endoderm

 Parietal adjacent to ectoderm



 Give an account of lateral folding of the embryo



Lateral body folding:

 Embryo’s body is turned into cylinder from sheet.

 Rolls up gut tube, nips off yolk sac

 Cuts intraembryonic coelom off from chorionic cavity

 Amniotic cavity surrounds embryo except at body stalk



 Be able to give an account of formation of the body cavities and how the lateral

plate mesoderm is so important in their development

Suzie Rayner









Human Life Cycle 5 –

The placenta: life support system of the fetus

 Draw simple sketches to show the differentiation of the chorion through morula

and blastocyst stages









In blastocyst:

 Inner cell mass develops into embryo, amnion and yolk sac

 Trophoblast (epithelial layer of the chorion) forms a fused layer

(syncytiotrophoblast), which eventually develops into the placenta



 Define cytotrophoblast and syncytiotrophoblast



Cytotrophoblast: inner layer of the trophoblast, consisting of cells which contribute to

the amnion and the syncytiotrophoblast.

Syncytiotrophoblast: outer layer of the trophoblast, consists of a syncytium of giant

cells and invades endothelium forming placenta

[Syncytium: many nuclei in same extent of cytoplasm]



 Describe the invasion of maternal tissues by the syncytiotrophoblast during

and after implantation

Suzie Rayner









 Syncytiotrophoblast burrows

through the uterine

epithelium to implant the

conceptus within the uterus

wall



[Resembles Cancer]



 invades uterine epithelium

and connective tissue

 invades and destroys small

vessels of uterus lining

(causing maternal blood to

flow into intervillous space)

 Widens uterine arteries

(increasing flow)

 Sheds fragments into

maternal blood



These fragments may metastasise to

mothers lungs or may reach systemic circulation



This causes pre-eclampsia:

 Increased blood pressure

 Protein leaking into urine

 Caused by metastasis of syncytiotrophoblast causing vascular disturbance or

insufficient placental invasion of uterine wall



 Compare the main sources of nutrition of the embryo or fetus before

implantation, during the first trimester and in the latter two trimesters



Before implantation:

 Embryo depends on its own reserves and fluid in the uterine tube

 No net. growth

 Expansion of blastocyst depends on the uptake of NaCl and water.



Week 2 – Week 8/12:

 Maternal tissue fluid and breakdown products within intervillous space



Week 8/12 onwards:

 Maternal blood flow through intervillous space



 Explain the terms “ectopic pregnancy” “placenta praevia” and indicate why

these conditions are dangerous

Suzie Rayner







Ectopic pregnancy: where the conceptus has implanted in the wrong place

Placenta praevia: when the placenta is sited so that it will block normal cervical delivery



Cause complications in labour, cause ruptures to mothers reproductive system…etc



 Explain why the term “haemochorial” is applied to the human placenta



There is no point where the fetal and maternal blood come into direct contact.



 Explain the origin of the intervillous spaces and the establishment of maternal

blood circulation through them



Chorionic villi are initially sprouts of the trophoblasts over the whole surface, but over

time they:

 retreat to basal side forming placental disc

 branch and acquire cores of connective tissue

 become vascularised and connected to embryos cardiovascular system



Allantoic vessels grow through the body stalk to the placenta, allowing all exchanges

with the mother.



Syncytiotrophoblast adapts blood flow (see previous learning objective)



Feto-maternal blood

interface:



Fetal blood circulates

through villous cores

in capillaries



Maternal blood flows

from dilated arteries

directly into

intervillous space

Suzie Rayner





 Define “decidualisation” and explain its importance



Decidualisation: normal response of endometrium to implantation

 modifies uterine arteries to ensure adequate blood flow

 provides protective mechanisms against rejection of feto-placental tissue by

mothers immune system



 Describe the origin of the amnion and outline the origins and importance of

amniotic fluid



Inner cell mass divides forming epiblast. Within the epiblast layer, many small fluid-

filled spaces appear which combine forming the amniotic cavity.



Amnion lines the chorion and contains amniotic fluid which the fetus floats it, drinks and

excretes into. (acts as a shock absorber)

 Sketch the tissue layers separating maternal from fetal blood









 Contrast the mechanisms by which (a) respiratory gases (b) electrolytes,

glucose and amino acids and (c) immunoglobulin G cross the materno-fetal

barrier



 Lipid soluble molecules are unrestricted (e.g. blood gases, ethanol, anaestetics,

steroids)

 Small uncharged molecules are unrestricted (e.g. water, urea)

 Large hydrophilic molecules are limited by membrane transporters (e.g.

glucose, amino acids)

 Proteins are held back unless there is a specialised transport system (e.g. for

IgG)



[N.B. Respiratory gases – unrestricted, electrolytes etc – limited, IgG – specialised

transport]

Suzie Rayner







 Indicate the endocrine roles of the placenta

 Suggest how the placenta may avoid attack by the maternal immune system



Secretes hormones which:

 maintain pregnancy

 promote lactation (prepare breasts for it)

 suppress menstruation

 Involved in initiation of labour

 Does not evoke maternal response to foreign tissue



 Outline how uterine blood loss is minimised when the placenta is delivered









 Know what proportion of the maternal cardiac output perfuses the uterus at

term

1/6 of maternal blood.







Human Life Cycle 6 –

The significance of the Y chromosome

 Explain the significance of the Y chromosome with particular reference to the

SRY gene.

 Describe the role of the SRY protein with respect to control over gonadal

development.



 Gonads derived from somatic mesenchymal tissues (forming matrix) and

primitive germ cells (forming gametes)

 Differentiation of gonads begins after Week 6 – formation of testes is actively

initiated (i.e. without activation, become female)



Within developing seminiferous cords (in males):

 Primordial germ cells → spermatozoa

 Mesodermal cells → Sertoli cells of seminiferous tubules

 Between seminiferous tubules, clusters of interstitial cells condense → Leydig

cells



SRY (sex determining region) gene is located on the Y chromosome

 SRY initiates formation of sertoli cells (expressed in male sertoli cells)



SRY protein is a transcription factor regulating other gene activity.

Suzie Rayner





 Draw a diagram illustrating the effects of androgens and Mullerian Inhibitory

Factor on fetal reproductive system development.









 Draw a diagram illustrating the development of Testicular Feminization

Syndrome (Complete androgen insensitivity syndrome – CAIS)









 Draw a diagram illustrating the consequences of excess androgens in a fetal

female genotype.



Excess androgens cause both male and female internal genitalia to develop, and male

external genitalia.

Suzie Rayner









Human Life Cycle 7 –

Development of urinary and reproductive organs

 Outline the development of the kidneys, ureters, urinary bladder and urethra.



Intermediate mesoderm gives rise to most of upper urinary and genital systems



Intermediate mesoderm gives rise to urogenital ridge, within which the nephrogenic

cord develops (kidney making).



Nephrogenic cord is source of most of urogenital system (exceptions: primordial germ

cells, lower urinary tract, perineum)



Development of kidneys:

 Sweeps cranio-caudially (top to bottom)



Region Event in kidney development

Cervical Never differentiates, regresses by Week 4

Thoraco-lumbar Mesonephros differentiates, but has mainly

gone by Week 8

Mesonephric duct Persists in males

Sacral mesonephros Appears in Week 5, becomes definitive

kidney



Ureter grows out from mesonephric duct.

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Maldevelopment of kidneys:



 fail to reposition (retain sacropelvic position)

 joined together – trapped below inferior mesenteric artery (horseshoe kidney)



Development of urinary bladder:



Allantois gives rise to most of bladder

[N.B. slender duct extending to umbilicus normally closes but if it does not it can cause

problems]



Cloaca becomes partitioned into urogenital sinus and rectal sinus.

[N.B. sometimes partitioning is incomplete and congenital fistula (opening) connects

urogenital and alimentary tracts]









Maldevelopment of ureters:



 Complete duplication

 Partial duplication (become one at some point)

 Ectopic (opening in abnormal place)



Position of kidneys and ureters:



Shared sections of ureter and mesonephric duct (in males) are absorbed into the back of

the bladder.



Ureters now open into bladder and the Mesonephric ducts into urethra.



Differential growth shifts metanephric kidneys from sacral site of origin to the posterior

wall of upper abdomen (up and backwards)

Suzie Rayner









 Outline the mechanism of differentiation of male and female structures in the

pelvis and perineum, including gonads, uterine tubes, uterus, vagina, vulva,

ducti deferentes, seminal vesicles, prostate, scrotum and penis.

 Outline gonadal descent and the formation of the inguinal canal.



In males – (the relationship of the gonads and the mesonephric duct.)

 Gonads develop medially to mesonephros kidney

 Most of mesonephros atrophies but parts between gonads and mesonephric

ducts persists

 These persistent parts will become efferent ducts between testis and ductus

deferens

 Developing testes link with mesonephric duct through some persistent

mesonephric tubules



 In 4th month testes descend into scrotum (through inguinal canal)

 Ductus deferens develop into seminal vesicles

 Urethra develops into prostate



In Females – (Paramesonephric ducts)

 Paramesonephric ducts develop in most lateral part of intermediate mesoderm

 In females they become uterine tubes, uterus and upper vagina

 [Not important in males]



 From Week 8 - 4th month, paramesonephric ducts link with each other and the

urogenital sinus to assemble definitive female structure

 Ovaries descend from origin, in upper lumbar region, to the pelvis



Primordial germ cells

 give rise to eggs and sperm

 arise from yolk sac

 in week 6 they migrate to genital ridge (via hindgut and mesentery)

 A few survive to form PGCs and somatic cells of next generation

Suzie Rayner









Sex determination – covered in HLC 5





Development of external genitalia:



 Same for both genders from weeks 3-6









Female:



Genital swelling →

labia majora



Cloacal fold → urethral

fold → labia minora



Urethra opens into

vestibule posterior to

clitoris

Suzie Rayner





Male:

Expansion of phallus



Fusion of urethral folds to enclose the penile

urethra (if incomplete – hypospadius)



Expansion and fusion of genital swellings to

form scrotum









 Outline the origin of the disorders of urogenital system development below



Duplication of a ureter

from mesonephric duct



Absence of kidneys





Pelvic and horseshoe kidneys

Pelvic – kidneys do not migrate from their origin

Horseshoe – kidneys are joined together and get stuck below the inferior mesenteric

artery



Polycystic kidneys





Wilm’s tumour of the kidney





Hypospadias

Incomplete fusing of the urethral folds



Mismatch between genetic and phenotypic sex (pseudohermaphroditism)

Androgen insensitivity (receptors don’t work)