How Deep Evolutionary History Affects Human Health (PDF)

How deep evolutionary history can affect human health Ahmed Ihab Abdelaziz MD, PhD Associate Prof. of Molecular Medicine 2024/2025 Objectives By the end of this session you should be able to: 1. Distinguish between competing theories to explain the singular origin of the eukaryotic cell 2. Unde...

How deep evolutionary history can affect human health Ahmed Ihab Abdelaziz MD, PhD Associate Prof. of Molecular Medicine 2024/2025 Objectives By the end of this session you should be able to: 1. Distinguish between competing theories to explain the singular origin of the eukaryotic cell 2. Understand how the evolutionary interactions between host cell and endosymbiont can drive the evolution of deep functional traits of all eukaryotes, such as sexes and senescence, and underpin the broad structure and physiology of modern mammalian cells 3. Appreciate that selection forces acting to maintain or improve fitness over generations can actually lower fitness within generations, especially after reproductive maturity 4. Understand how different systems, such as fertility, aerobic capacity and environmental adaptability can impact on the diseases of old age. The three domains of life An ‘evolutionary scandal’ All complex life is eukaryotic. The eukaryotic cell only arose once in 4 billion years. Eukaryotes share universal traits like the nucleus, mitosis, sex, phagocytosis, organelles, etc. Prokaryotes show virtually no tendency to evolve morphological complexity, or any these eukaryotic traits. BUT if each these traits evolved step by step, and each step has a selective advantage, why did none evolve in prokaryotes? A black hole at the heart of biology All eukaryotes share traits essentially absent from prokaryotes: Nucleus, nuclear membrane, nuclear pore complexes, nucleolus, straight chromosomes, telomeres, introns and exons, spliceosomes Separation of transcription (nucleus) and translation (cytosolic ribosomes) Reciprocal sex (two-step meiosis and syngamy), mitosis, tubulin spindle Dynamic cytoskeleton, motor proteins, eukaryotic cilia and flagella Phagocytosis Endomembrane systems, (ER, golgibody, lysosomes, mitochondria) Generally much larger genomes and cell volumes All eukaryotes have or had mitochondria Microsporidia Entamoeba (derived fungi) Giardia lamblia (mitosomes) (mitosomes) Trichomonas (hydrogenosomes) These cells were all thought to be true evolutionary intermediates but turn out not to be: they are all ecological intermediates that became simpler. All of them once had mitochondria and lost them by reductive evolution. The Last Eukaryotic Common Ancestor therefore had mitochondria Some genomic evidence suggests that the eukaryotic cell arose via a stochastic (and very rare) endosymbiosis between two prokaryotes The ‘search engine’ of natural selection, acting on vast populations of cells over billions of years, does not intrinsically give rise to complexity A cell within a cell What did mitochondria do for us? 1.Compartmentalisation? No, many prokaryotes compartmentalise themselves 2.Aerobic respiration? No, many prokaryotes respire oxygen and many mitochondria don’t 3.Protection against oxygen toxicity? No, mitochondria are the main source of ROS leak 4.Speed of respiration? No, gram per gram many prokaryotes respire faster Cells need genes to control respiration Mitochondrial genes enabled eukaryotes to expand in size over 4-5 orders of magnitude Paramecium What happens in eukaryotes? A cell within a cell – has it’s own cell division machinery enabling it to divide independently within the host cell Reductive evolution of endosymbiont genomes Rickettsia Carsonella Buchnera Wolbachia Unlike extreme polyploidy, individual cells can compete with each other, and the fastest replicators (with the smallest genomes) WIN. Consequence: genome size gets smaller Why endosymbiosis is necessary?  It follows that… Complex life requires genomic asymmetry–giant nuclear genomes supported by tiny mitochondrial genomes Mitochondrial and nuclear genes MUST work together (co-adapt) for respiration to work BUT the two genomes differ in tempo and mode of evolution –there must be selection for function What if the genomes don’t match? APOPTOSIS High ROS leak, low ATP, loss of cytochrome c = apoptosis ROS = reactive oxygen species, e.g. superoxide, hydrogen peroxide Explains the double role of cytochrome c in respiration and apoptosis –a discovery first greeted with ‘general stupefaction’ (Hengartner, Nature 1998) Why does apoptosis involve mitochondria and the respiratory protein cytochrome c? This arrangement makes perfect sense if mitonuclear coadpatation is central to cell physiology If the two genomes do not function well together, the biophysical outcome is high ROS leak, oxidation of membrane lipids, release of cytochrome c, and apoptosis Apoptosis can then be seen as a type of functional selection for mismatched ‘The end of a cell’ by Odra Noel mitochondrial and nuclear genomes The price of selection for mitonuclearmatch: INFERTILITY Oocyte maturation and atresia – But can’t select for intergenomic coadaptation during Dictyate as nuclear background is not yet determined Embryonic development –40% of pregnancies end in early occult miscarriage (Zinaman et al, 1996). Childhood/adult life –mitochondrial diseases lower fecundity and survival Apoptotic threshold is variable Conclusions The eukaryotic cell arose ONCE in 4 billion years of evolution, possibly as a stochastic consequence of an endosymbiosis between two prokaryotes The distinction between eukaryotes and prokaryotes is not the nucleus alone but the extreme genomic asymmetry in which tiny mitochondrial genomes support a massive nuclear genome A ‘mosaic’ respiratory chain is necessary for the existence of complex life ROS leak enables selection for mitonuclear coadaptation via apoptosis Species with high aerobic demands should have a low apoptotic threshold Low threshold = long lifespan, low fertility, low adaptability, and vice versa Body Plan Function and homeostasis (I-2.17)2024/2025 Safaa Sharrah Lecturer of Physiology SOM Objectives By the end of this lecture, the student should be able to: Recognize the complementarity of structure and function. Identify the different levels of structural complexity. By the end of this section, the student should be able to: Understand the principle of homeostatic balance and its role in biological system. Recognize positive and negative feedback, feed forward, receptors and set-points. Recognize steps of homeostasis at different levels (cellular, organ, and whole body). Describe the consequences of de-compensation (imbalance, signs and symptoms of disease). Understand why homeostasis is not just a cellular mechanism.  Definitions Anatomy : Physiology: The study of the The study of the function structure of body parts of living organisms. and their relationships to one another.  Complementarity of Structure and Function The function is dependent upon structure – Anatomy and physiology are truly inseparable sciences. – The structural characteristics contributing to the physiologic function. Levels of Structural Complexity Homeostasis: Getting The Balance Right  Environmental Controls Unicellular organisms have no control over their environment  they only live where the conditions allowed. Human cells are surrounded by extracellular fluid (1/3rd of body fluid) which forms an internal environment Mammals have the ability to maintain their internal environments within narrow limits in a wide variety of external conditions humans are allowed to survive in a range of climates.  Homeostasis Cells are capable of living, growing and performing their special functions so long as the proper concentrations of the constituents of the ECF are available. The ECF is called internal environment of the Body. Definition: it is the maintenance of a constant condition in the internal environment  Homeostasis What are the characteristics of the extracellular environment? 1- Ion concentrations: Na+ = 145mM K+ = 4mM 2- Osmolarity = 290mosm/L CO2 3- Temperature = 37.1 oC Glucose 4- pH = 7.4  The Advantages of Homeostasis: (1) Increased chances of survival. (2) Allows freedom to work and live in a great variety of climatic conditions. (3) Permit proper functioning of the brain. the body can resist changes in the internal environment but to a variable range and time. Almost all diseases are failures of homeostasis. Stimulus and Response Response Stimulus  Homeostatic Mechanisms Stability comes from the ability of a system to measure any change (=variation), detect any errors when the system is not in balance and be able to counteract to correct any error to achieve balance again. To achieve this, we need:  variable Variable Sensor  sensor  integrator Integrating Effector  effector centre 1- Receptors = sensors or detectors Variable Sensor detect changes in the environment both outside and inside the body and provide information Integrating Effector 2- Controller = control centre centre or integrating centre receives the signal information from the sensors about the change the integrator compares the sensor's input and the set point. If there is a difference between sensor's input (actual change) and the set point, it generates the signal necessary for correction of the error. 3-Effectors respond to signal from the centre to correct the error.  Homeostatic Examples Controlled variables Control System Glucose Pancreas, gut, liver Temperature Skin, skeletal muscle, hair Osmolarity Kidney, thirst Blood pressure Heart, vasculature Oxygen and CO2 Lungs, blood pH Lungs, kidney  Control Mechanisms A chain of events... – Stimulus produces a change in a variable – Change is detected by a sensory receptor – Sensory input information is sent along an afferent pathway to control center – Control center determines the response – Output information sent along efferent pathway to activate response – Monitoring of feedback to determine if additional response is required NB: Aging reduces our ability to maintain homeostasis Heat stress Sensors Sensors measure controlled variables. Receptors are common sensors as they measure controlled variables by changing intracellular activity in response to extracellular changes. Nerve cells encode their information about controlled variables through the frequency of action potentials. Many sensors are specialised ion channels. 1) Negative Feedback Variable Sensor It provides a mechanism for change in relation to the size of the initial Effector Integrating variation. centre i.e. the bigger the change the bigger the negative feedback effect. It causes the system to change in the opposite direction from the stimulus Integrating Blood glucose centre Glucostat Blood Glucose Regulation The body requires glucose in order to create ATP. The amount of ATP demanded will fluctuate the body regulates the glucose availability to maximise its energy making potential. Receptor Liver Two hormones are responsible for controlling increase Glucose > Glycogen the concentration of glucose in the blood = insulin and Glucose Glucose glucagon. Normal Normal The principle of negative decrease Glycogen > Glucose feedback control of blood Receptor Liver glucose levels. Temperature Regulation  Set Point Biological systems are intelligent and Variable normally DO NOT overcompensate. Set point Set point in biological systems effectively is a range of “normal” values. Disturbance Time blood glucose concentration range 4.4 to 6.1 mmol/L (82 to 110 mg/dL) Variable The set point can be altered by various Normal factors: in fever, the temperature Range controller re-sets to a higher value! Disturbance Time  Dual Effectors Blood Glucose Temperature Insulin Sweat 370C Shiver Glucagon Antagonistic effectors are used to increase the precision of control in homeostatic systems. The effects are not all or nothing but exist as a constant interplay to achieve a normal range.  2) Feed-forward Anticipatory changes are important Ex:  when we eat  forward signals are sent to allow the GI tract to be ready expecting glucose & stimulate insulin secretion allowing glucose uptake =The Incretin Effect  when we eat salty food we get thirsty to drink water before the NaCl levels in the blood have had time to change.  we put on warmer clothing before we get too cold, this an anticipatory behaviour. 3) Positive Feedback Also, present in the body, but they are not part of homeostatic mechanisms. They de-stabilise, rather than stabilise and accelerate transitions between different states, often amplifying signals. change occurring in the same direction as the original stimulus. Positive feedback mechanisms usually control infrequent events such as blood clotting or childbirth  Contractions of uterus during labour are stimulated by the baby’s head pressing on the cervix.  Positive Feedback Mechanism Break or tear in blood vessel wall Clotting occurs as platelets adhere to site and release chemicals Released chemical attract more platelets Clotting proceeds until break is sealed by newly formed clot  Sensors and Effectors The liver acts as a storehouse for glycogen, the storage form of glucose. When either insulin or glucagon target the liver.  Sensors and Effectors When either insulin or glucagon target the liver, the following occurs: Insulin - is released due to ↑ glucose levels promotes the conversion of glucose into glycogenthe excess glucose can be stored for a later date in the liver. Glucagon - is released due to ↓glucose levels promotes the conversion of glycogen into glucose the lack glucose can be compensated for by the new supply of glucose from glycogen.  Loss of Homeostatic Control Diabetes Mellitus type 1: insufficient insulin to be produced  glucose cannot be converted into glycogen  injections of insulin after meals are needed to maintain the glucose storage needed in emergencies. Diabetes Mellitus type 2: insufficient response to insulin is the problem  glucose cannot be converted into glycogen and stored  the patient takes insulin sensitizers to increase the magnitude of their normal homeostatic response to raised blood glucose.  Levels of Control Whole body homeostasis Most whole body homeostatic mechanisms involve a joint action of autonomic nervous system, endocrine system and behavioural reactions such integrated responses include ionic balance, blood pressure, blood volume. Local homeostasis (organ-specific) In the lung when low oxygen levels  blood vessels constrict and move blood flow to areas with higher oxygen levels to ↑oxygen uptake into the bloodstream. Cellular homeostasis After a nerve cell is activated and depolarised  potassium channels open to normalise the resting membrane potential.  Integrated Homeostasis In emergencies: Adrenaline is released by the body to override the homeostatic control of glucose promote the glycogen breakdown into glucose to be used in the emergency known as 'fight or flight reactions'. Adrenaline is secreted by the adrenal glands ↑ metabolism, breathing and heart rate. Once the emergency is over, and adrenaline levels drop, the homeostatic controls are once again back in place.  Consequences of Homeostasis Stability of all body functions is maintained by numerous closed loops with negative feedbacks= the system responds in by cancelling any deviations from the optimal level. As long as homeostatic systems cope with their tasks we stay healthy. However, homeostasis only works within tolerable limits, where extreme conditions occur may disable the negative feedback mechanisms. Failures in homeostasis diseases and may be lethal. Medical interventions may be designed to restore homeostasis (blood-pressure-lowering drugs). However, drugs may cause side effects due to unwanted interactions with other homeostatic mechanisms.  References: http://AnatomyandPhysiology.com/ap-levels-of -structural- organization www.d.umn.edu>documents>chp1 Textbook Of Medical Physiology: Guyton & Hall.  Origins of Body Form The First Month of Human Life (2.19) Lecture (3) Anatomy Division  Objectives By the end of this session (the 3 lectures) you should be able to describe the: Production of the gametes (eggs and sperm) Fertilization, implantation and some causes of infertility Methods of contraception Formation of the germ layers Formation of the body plan Origin of organs and tissues 2nd Week of Development Bilaminar Germ Disc Extraembryonic cytoplasm Chorion I. Formation of bilaminar embryonic disc * Implantation of the blastocyst is completed during the second week. * Concurrently, morphologic changes occur in the embryoblast resulting in the formation of a flat, almost circular, transparent bilaminar embryonic disc, consisting of two layers: 1. Epiblast (future ectoderm): consists of high columnar cells related to the amniotic cavity. 2. Hypoblast (future endoderm): consists of small cuboidal cells adjacent * The embryonic disc gives rise to the germ layers that form all tissues and organs of embryo. * As implantation of the blastocyst progresses, a small space appears in the embryoblast→ the primordium of the amniotic cavity (the cavity that surrounds the fetus later on). * The outer surface of the chorionic vesicle shows a large number of proliferations termed chorionic villi  Week 3 Trilaminar germ disc Gastrulation & Neurulation  Gastrulation *Def.: This is the process by which the bilaminar embryonic disc is converted into a trilaminar embryonic disc. * It is considered the beginning of morphogenesis (development of body form). * During this period, the embryo may be referred to as a gastrula. * Cells from the epiblast, displace the hypoblasts, forming the embryonic endoderm & also give the third layer which is the embryonic mesoderm. * The cells remaining in the epiblast form the embryonic ectoderm. * Thus, the epiblast, through the process of gastrulation, is the source of all the germ layers, and cells in these layers will give rise to all the tissues and organs in the embryo. Folding  Folding is the process by which the trilaminar embryonic disc becomes folded by a head fold, a tail fold and 2 lateral folds so, getting the cylindrical shape of the embryo The endoderm becomes enclosed inside the embryo forming the gut tube The ectoderm covers the embryo from the outside The amniotic sac surrounds the embryo Derivatives of the 3 Germ Layers Ectoderm → deal with outside – Surface →Skin + appendages + All orifices lining ( external ear – eye – nose – mouth – glands (salivary + ant. Pituitary) – anal canal – urethra) – Neuro Neural tube → Brain & sp.cord (CNS), + retina of eye + post. pituitary - Neural crest Endoderm → provide & rid Mesoderm → support Ectoderm → deal with outside Endoderm → provide & rid – Gastro-intestinal tract (GIT) & its glands (Liver & pancreas) – Respiratory tract – Lower urinary tract (urinary bladder, most of urethra, vagina & prostate) – Derivatives of pharynx (middle ear, tonsils, parathyroids & thymus) Mesoderm → support Ectoderm → deal with outside Endoderm → provide & rid Mesoderm → support – Musculoskeletal: all muscles except those of iris + bones + cartilages + joints + ligaments + connective tissue (CT) – Cardiovascular system (CVS) – Upper urogenital tract (Kidneys & ureters) – Serous membranes (pericardium, pleura, peritoneum) – Dura mater, adrenal cortex, microglia  Summary How a sperm & an ovum are formed= Gametogenesis How a sperm & an ovum meet= Fertilization→ zygote Stages of cleavage→ Blastocyst How & where a blastocyst is implanted in the wall of the uterus Methods of contraception Formation of a bilaminar then a trilaminar embryonic disc then the process of folding Derivatives of each of the three germ layers Thank you  Origins of Body Form The First Month of Human Life (2.19) Lecture 2 Anatomy Division Date : xx / xx / xxxx  Objectives By the end of this session (the 3 lectures) you should be able to describe the: Production of the gametes (eggs and sperm) Fertilization, implantation and some causes of infertility Methods of contraception Formation of the germ layers Formation of the body plan Origin of organs and tissues Fertilization What is fertilization? Where does it occur? How? Results…. Definition: The process of union between the male & female gametes to form the zygote Site: Lateral 1/3 of the uterine tube (Ampulla)  Steps of Fertilization: I. Preparatory steps: Journy of the sperm to reach the site of fertilization: * Sperm→ vagina→ uterus→ uterine tube (by movement of tail + uterine contractions) * Around 300 million ejaculated sperms→ Around 300 reach site of fertilization & only 1 penetrate the 2ry oocyte 2 processes: 1. Capacitation (maturation or activation): Removal of glycoprotein coat 2. Acrosomal reaction: Release of acrosomal enzymes to penetrate the oocyte II. Actual steps: Penetration of the head & neck of the sperm into the oocyte→ rounded= Male pronucleus Male & Female pronuclei (each containing 23 (n) chromosomes) unite to form 1 nucleus (46 - 2n)  The results of fertilization: Stimulates the completion of the 2nd maturation division→ Mature ovum +2nd polar body Restores the normal diploid number of chromosomes (46). Determination of the sex of the embryo. The sex chromosome (Y or X) carried by the sperm determines embryonic sex. Initiation of cleavage ( Segmentation). Zona & cortical reactions occur to prevent fertilization of the same ovum by more than one sperm.  Cleavage or segmentation of the zygote Definition: Repeated mitosis so that a unicellular zygote → multicellular mass of embryonic cells (Blastomeres) It starts 30 hours after fertilization * The zona pellucida keep blastomeres adherent together & prevent the adhesion of blastomeres to the uterine tube * Blastomeres are considered Totipotent  Steps: 1. Repeated mitotic division of Zygote + movement towards the uterine cavity by tubal cilia 2. 2- cell stage→ 4-cell….→ 12-16 cell stage= Morula after 72 hours 3. Morula reaches uterine cavity on the 4th day of fertilization, undergo accumulation of fluid: Blastocyst  Results of cell cleavage: in number of cells + in size of cells to reach the normal cell size of the species  Blastocyst formation How does it form? What are the changes that happen to the morula? ▪ Zona pellucida starts to degenerate at the end of 5th day. Fluid pass through degenerating zona to form multiple spaces between cells of the morula. Gradually, those spaces fuse together to form a single cavity, called blastocele. This stage is named blastocyst. Could you describe the blastocyst? Blastocyst is composed of: (description) 1) Outer cell mass (trophoblast) (becomes the fetal portion of the placenta). 2) Inner cell mass (embryoblast) (becomes the embryo) grouped at the embryonic pole of the conceptus, the other pole is called abembryonic pole. 3) Blastocele is the cavity of the blastocyst. Implantation  Implantation Definition: The process of embedding of the free blastocyst into the uterine wall. Site: the normal site is the endometrium of the upper part of the body of the uterus mainly in the posterior X wall, near the midline, near the fundus.  Steps: 1. Starts at 6th day after fertilization, the trophoblastic cells over the embryonic pole adheres to the uterine wall, erode the endometrium and the whole blastocyst progressively penetrates it 2. About the 9th day the blastocyst becomes completely implanted. 3. The trophoblastic cells rapidly proliferate, become arranged into 2 layers: a. An outer Syncytial trophoblast: a mass of protoplasm with randomly dispersed nuclei. b. An inner cytotrophoblast: formed of cells with well- defined walls. 4. The site of entry of the blastocyst is closed by a fibrin clot. 5. The blastocyst is getting its nutrition from the eroded maternal tissues.  Abnormal sites of implantation *These are sites other than the normal site of implantation A. Intrauterine sites: (placenta praevia): * Implantation inside the endometrium very close to the cervix of the uterus (in the lower uterine segment). It includes: a. Placenta praevia lateralis = just above internal os b. Placenta praevia marginalis = around internal os. c. Placenta praevia centralis = covers internal os. B. Extra-uterine sites: 1. Tubal pregnancy: in the uterine tube.(DD:appendicitis) 2. Abdominal pregnancy: in the abdominal cavity. 3. Ovarian pregnancy: on the surface of the ovary. ** N.B.: Implantation outside the cavity of the uterus leads to Ectopic Pregnancy which cannot reach full- term due to inadequate nutrition.  Methods of Contraception Hormonal methods: to prevent ovulation, e.g. oral contraceptive pills, skin patch & injectable contraceptives Intrauterine device (IUD): releases hormones that inhibit sperm transport & capacitation also, it inhibits implantation Barrier methods: inhibits sperm transport, e.g. male condom, diaphragm & cervical cap Spermicides: kill sperms, they are in the form of cream, gel, suppository, foam) Natural methods: e.g. family planning (safe period), breast feeding Sterilization: inhibits fertilization by tubal ligation in females & vasectomy in males Thank you  Origins of Body Form The First Month of Human Life (2.18) Lecture 1 Anatomy Division Date : xx / xx / xxxx  Objectives By the end of this session ( the 3 lectures) you should be able to describe the: Production of the gametes (eggs and sperm) Fertilization, implantation and some causes of infertility Methods of contraception Formation of the germ layers Formation of the body plan Origin of organs and tissues  Gametogenesis ▪ Definition: Is the formation of male and female gametes (sperms &eggs) by a process known as spermatogenesis and oogenesis, respectively. What is spermatogenesis? Process of formation of complete motile spermatozoa from primordial germ cells (spermatogonia). When? Puberty→ Old age Where? Seminiferous tubules of testis How (STEPS)?  Steps of Spermatogenesis Proliferation: Growth: Maturation &Transformation: Spermatogonia Daughter a) 1st maturation division➔2ry (44xy) divide spermatogonia spermatocytes by mitosis into enlarges b) 2nd maturation division➔ daughter forming 1ry spermatids spermatogonia spermatocyte (44xy)  How? STEPS of Spermatogenesis 1. Proliferation: → Daughter spermatogonia (46- diploid) 2. Growth:→ Large 1ary spermatocytes (46-diploid)  How? STEPS of Spermatogenesis 3. Maturation:→ Meiosis I; 2 2ry spermatocytes (23-haploid)--- Meiosis II (mitosis); each→ 2 spermatids (23-haploid) 3. Transformation (Spermiogenesis)  4. Transformation (Spermiogenesis) Nuclear material (chromatin) gets condensed and the nucleus moves towards Golgi apparatus forms the acrosomal cap that one pole of the cell to form the head of covers anterior two-third of the nucleus. the spermatozoon. The remaining part of the axial filament elongates to form the tail. Most of the cytoplasm of spermatid is shed off but the cell The part of the axial filament between the membrane remains, which The Centriole gives rise to the axial filament. neck and annulus becomes surrounded by the covers the entire spermatozoon. mitochondria, and together with them forms the middle piece.  To sum up:  Structure of a sperm: 1.Head: Acrosome + Nucleus 2.Neck: Follows the head & contains the centriole. 3.Body: Middle piece containing mitochondria 4.Tail: end piece containing the axial filament  Male fertility Depends on the number, shape and motility of sperm. Normal number : is 100 million/ml or 300-500 million/ ejaculate. - Sterile males produce less than 10 million sperm/ml of semen - Abnormal forms(shape) should not exceed 10%. - motility : normally 70% are motile. What is oogenesis? Process of differentiation of mature oocyte (ready for fertilization) from primordial germ cells (oogonia). When? Begins: 3rd month of intrauterine life → birth (pause) then after puberty (during each ovarian cycle) and after fertilization Ends: at menopause Where? Ovary How (STEPS)?  Two Prenatal Stages Postnatal Maturation Proliferation Growth 2nd maturation division 1st maturation division (at fertilization) (at ovulation) 13  How? STEPS of oogenesis oogonia During fetal life (prenatal maturation) 1. Proliferation: in early fetal life→ Daughter oogonia (46-diploid) 2. Growth:→ Large 1ry oocytes (46)→ begin 1st meiotic division (before 5th month, all are 1ry oocyte, no oogonia)  How? STEPS of oogenesis oogonia Postnatal maturation 1. Completion of 1st meiotic division:→ 2ry oocyte (23-haploid) + 1st polar body (haploid) (occurs at puberty, ovarian cycle) 2. Second meiotic division: → mature ovum (23-haploid) + 2nd polar body (occurs after ovulation, only if fertilization occurs)  Number of 1ry oocytes: at puberty: 40 000 Number of ovulated 2ry oocyte in the fertile period of a woman around 480 (12x40); this is reduced by contraceptive pills, pregnancy & unovulatory cycles the rest become atretic The 1st meiotic division: is a long process (may be up to 45 yrs)→ this may lead to high frequency of meiotic error in increasing maternal age  To sum up: The 1st meiotic division: long (up to 45 yrs)→ high frequency of meiotic error in increasing maternal age→ The primary cause of Down syndrome (Trisomy 21) is maternal meiotic nondisjunction ❑ If oocyte with 24 chromosomes is fertilized by a normal sperm (23 chromosomes), a zygote with 47 chromosomes is produced (i.e., trisomy).  The various stages of development of Ovarian Follicles and Ovulation: a) Primordial follicles → Primary follicles →secondary follicles → Graafian follicle (Primary oocyte + The follicular cells proliferate to form The small fluid-filled cavities appear The Graafian follicle surrounding single layer of several layers.The follicular cells are now between the follicular cells. These enlarges and becomes so flat epithelial cells) called granulosa cells. between the cavities fuse together to form a large big that it not only granulosa cells and the primary Oocyte cavity—the antral cavity/antrum and reaches the surface of there is a membrane which is termed zona the follicle is termed secondary the ovary but also forms pellucida (vesicular) follicle. a bulge on the surface of ovary.  Ovulation: Definition: Rupture of Graafian follicle & discharge of 2ry oocyte Onset: 14th day of menstrual cycle Signs: - increase of the body temperature - Sometimes pain: mittelschmerzen (German for “middle pain”) ▪ Steps of ovulation 1. 2ry oocyte escapes after rupture of Graffian follicle to enter uterine tube 2. If fertilization occurs, 2nd meiotic division occurs to give mature ovum & 2nd polar body If no fertilization→ it dies ▪ Steps of ovulation(cont.): 3. The follicle under the effect of LH hormone→ Luteinization= lipid deposition (yellow in colour) so named: Corpus Luteum which secrete progesterone Fate of Corpus Luteum: 1. If fertilization → Corpus luteum of pregnancy (secretes progesterone for 3-4 months till formation of placenta). 2. If no fertilization→ fibrosis→ Corpus luteum of menstruation or Corpus albicans  Structure of the released mature ovum: a) Nucleus that has the hereditary material of the mother (22 autosomes & X-Chromosome). i.e 23 ch b) Large cytoplasm which is the initial source of nutrition of the zygote c) Cell membrane. d) Zona pellucida: It is the glycoprotein coat around the oocyte. It carries sperm receptors that attracts sperms prior to fertilization. e) Corona radiata: it is the outer cover that is formed of follicular cells derived from the ovary. Thank you