“Inheritance” in images, from Darwin’s “tree of life” to DNA’s iconic crystallography to the epigenetic dynamicsHowever, the script needs to be interpreted and receives meaning only from the interplay with the environment
Epigenetics is the study, in the field of genetics, of cellular and physiological phenotypic trait variations that are caused by external or environmental factors that switch genes on and off and affect how cells read genes instead of being caused by changes in the DNA sequence. -Wikipedia
"Epigenetics refers to genetic factors that change an organism’s appearance or biological functions without changing the actual DNA sequence. In other words, gene expression changes but the genes themselves don’t. Epigenetics adds an additional level of complexity to the genetic code." - Public Health Cafe
Overview of epigenetics and its role in diseaseGarry D. Lasaga
Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
Epigenetics is the study, in the field of genetics, of cellular and physiological phenotypic trait variations that are caused by external or environmental factors that switch genes on and off and affect how cells read genes instead of being caused by changes in the DNA sequence. -Wikipedia
"Epigenetics refers to genetic factors that change an organism’s appearance or biological functions without changing the actual DNA sequence. In other words, gene expression changes but the genes themselves don’t. Epigenetics adds an additional level of complexity to the genetic code." - Public Health Cafe
Overview of epigenetics and its role in diseaseGarry D. Lasaga
Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes. - [https://www.whatisepigenetics.com/fundamentals/]
Author of this presentation: The University of Western Australia
This presentation is about Genomic imprinting. Genomic imprinting is only found in eutherians. In next few slides we'll try to understand this phenomena.
'GENETICS OF MALE & FEMALE INFERTILITY.pptxRahul Sen
This presentation briefs about an important aspect of infertility which deals about genes and its occurrence in future progeny. Genetics of Male & Female infertility which is not always discussed usually until unless a couple doesn't exhibit pregnancy losses or a major cause of infertility. lets read about Genetics of male and female infertility. Happy Reading <3
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes. - [https://www.whatisepigenetics.com/fundamentals/]
Author of this presentation: The University of Western Australia
This presentation is about Genomic imprinting. Genomic imprinting is only found in eutherians. In next few slides we'll try to understand this phenomena.
'GENETICS OF MALE & FEMALE INFERTILITY.pptxRahul Sen
This presentation briefs about an important aspect of infertility which deals about genes and its occurrence in future progeny. Genetics of Male & Female infertility which is not always discussed usually until unless a couple doesn't exhibit pregnancy losses or a major cause of infertility. lets read about Genetics of male and female infertility. Happy Reading <3
Human reproduction is remarkably inefficient; Only 420 are born alive out of 1000 fertilizations, nearly 70% of human conceptions do not survive to live birth. The stillbirth in india is highest in the world 7% to 14% in different states Odisha 8% Karnataka 14% (of course reported only) Recurrent pregnancy loss is a psychologically stressful diagnosis for couples, in approximately 50% of cases, no cause will be found. The number of evidence-based practices available for guidance is limited. This confluence of factors presents a challenge for clinicians. However, in studies of interventions aimed at reducing rates of miscarriage in women with otherwise unexplained RPL, control groups experience a live birth rate of up to 87% with no intervention. Thus, one of the most significant things we can do when caring for these complex patients is to offer them emotional support and accurate information. As more work is done in this emerging area of reproductive science, we will be able to shed more light on this complex problem.
Prof. Dr. Vladimir Trajkovski - Epigenetics of ASD-10.05.2019Vladimir Trajkovski
President of MSSA Prof. Dr. Vladimir Trajkovski presented this topic "Epigenetics of Autism Spectrum Disorders" at the mini simposyum in Voerandaal, Holland, organized by ReAttach Academy at May 10th 2019.
Sperm DNA Fragmentation : Role in natural and assisted conception: Recent adv...Shivani Sachdev
Male factor infertility is responsible for >40% of couples presenting for ART. Conventional SA continues to be the only routine test to diagnose this condition. Current SA is based on 5th edition of the WHO manual (2010) . All normal values shifted to lower centile compared to previous edition. Less men now classified as infertile (Murray et al 2012). Sperm DNA damage - used to denote abnormal genetic material which in turn may lead to male sub fertility/ IVF failure / miscarriage.
DNA Fragmentation Index of Sperm - Expressed as DFI- or percentage of the number of cells with defects in protamination of DNA structure in the evaluated sperm cells
The integrity of paternal genome is of paramount importance in the initiation of viable pregnancy. The fragmented DNA is incompatible with normal embryonic development
Sperm chromatin anomalies are often present in men with abnormal semen analyses 8% of men with normal semen parameters have abnormal sperm DNA integrity
Zini A.Biologic variability of sperm DNA denaturation in infertile men. Urology 2001
We discuss the various tests used and recent concepts and techniques and what are the newer treatment options
THE ASSISTED REPRODUCTION TECHNOLOGY REGULATION RULES, 2010
Members of drafting committee11 members
1- Sr Advocate Supreme Court of India
2 – Public Interest Legal Support and Research
3 – Dept of Family Welfare, M of Fam Wel and Research
5 – experts from the field of Reproductive Medicine
Ovarian Drilling Do's & Don'ts - By Dhorepatil BharatiBharati Dhorepatil
Rotterdam Criteria 2003
The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
March 2–3, 2007, Thessaloniki, Greece.
Human Reproduction 2008
Luteal Phase - Clinical Point of View - By Dr Dhorepatil BharatiBharati Dhorepatil
Maintenance of pregnancy
Corpus luteum Progesterone
After ovulation ~ during the early first trimester ~ until placental function established
Removal of the corpus luteum spontaneous pregnancy loss
Ovarian progesterone production implantation & early pregnancy
Role of decreased androgens in the ovarian response to stimulation in older women
Part I: Effects of testosterone (T) on preantral and antral follicles
Part II: How to improve ovarian response ?
Exogenous testosterone
DHEA
Aromatase inhibition (AI)
LH/HCG
Growth hormone (GH) / IGF-I
Indivisualization of Ovulation Induction - Dr Dhorepatil BharatiBharati Dhorepatil
IVF started to develop fast with the aim of maximizing pregnancy rates per cycle
Higher number of oocytes and thus more embryos
Use of unphysiological high doses of gonadotropins
Time consuming protocols
Higher costs
Patient discomfort
Higher risk of OHSS
Very high risk of multiple gestation
MONITORING PITUITARY DOWN-REGULATION
If GnRH Agonist is started in the late luteal phase a menstrual bleeding normally indicates that the estrogen is low and FSH can be started.
Blood tests will clearly confirm down-regulation – ovarian/pituitary hormones.
Ovulation Stimulation Protocols for IUI - Dr Dhorepatil BharatiBharati Dhorepatil
What are important factors to be considered important
Ovarian reserve
Previous ovarian response
Basic hormone profile
Role of LH
Trigger
Luteal phase support
Pregnancy rate/cycle
Patient selection and work-up
Ovarian stimulation
Monitoring of follicular growth and endometrial development
Timing of insemination
Number of inseminations
Semen preparation
Insemination procedure
Luteal support
Ovulation Induction - Simplified - Dr Dhorepatil BharatiBharati Dhorepatil
What are factors to be considered
Ovarian reserve
Previous ovarian response
Basic hormone profile
Role of FSH & LH
Trigger
Luteal phase support
Pregnancy rate/cycle
Ovarian reserve tests provide an indirect measure of the cohort of recruitable antral follicles present in the FSH window at the beginning of each menstrual cycle..Functional Ovarian Reserve
Why we need to predict?
Hormone defects may cause severe neurological, metabolic or cardiovascular consequences and lead to the early onset of osteoporosis
Psychological Depression
Low levels of self esteem and Life satisfaction
Sexual Dysfunction
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
3. “Inheritance” in images, from Darwin’s
“tree of life” to DNA’s iconic
crystallography to the epigenetic dynamics
However, the script needs to be
interpreted and receives meaning only
from the interplay with the environment
4. Things become more complex with the
discovery of DNA’s inherited mutations to
“metabolism”,
with transposable elements, repair,
methylation, miRNA, &
histone acetylation,
i.e. INTERPLAY WITH THE (internal and external)
ENVIRONMENT
7. Infertility genetic counseling aims to answer
two fundamental questions
1. Does the infertility have a genetic origin
and is it related to inheritance?
2. Does the procedure used in infertility
treatment increase the risk of genetic
disorders in the child?
8. Does the infertility have a genetic origin
and is it related to inheritance?
• Male Infertility…Genetic Factors..Common
• Female Infertility..Genetic Factors.Less common
• Recurrent Pregnancy loss.. Chromosomal
abnormalities in 5-6 % of males or females
9. Male Infertility
• Azoospermia Obstructive.. Congenital
bilateral/unilateral absence of
vas deferens :CFTR mutation
Nonobstructive
Y microdeletion
Chromosomal Abnormality
• Oligospermia
• Normal sperm count.. Chromosomal abnormality
10. Azoospermia : Obstructive
• 70.95 % of the CBAVD patients carried a
mutation on both CFTR genes,
• 15.90 % of the CBAVD patients carried a
mutation on one CFTR gene.
Cuppens H, Cassiman JJ.CFTR mutations and polymorphisms in male infertility.Int J
Androl. 2004 Oct;27(5):251-6. French study
Genetic counseling of CFTR mutation is
complex and difficult,but must
11. CBAVD patients usually have one severe, one
mild or two mild mutations.
CFTR mutations can be divided into five
classes, from severe to mild phenotypes
12. • The female partner of the CBAVD patient carrying CFTR
mutation should be screened for the mutations in CFTR
gene before ART procedures.
• When both partners are carriers of CFTR mutations, PGD
or prenatal diagnosis for CF should strongly be
recommended during genetic counseling as the fetus is at
risk of CF disease.
13. Azoospermia : non Obstructive
• The frequency of chromosomal disorders is
15-20 % in nonobstructive azoospermia patients
• Johnson MD: Genetic risks of intracytoplasmic sperm injection in the treatment of male
infertility: recommendationsfor genetic counseling and screening. Fertil Steril 1998; 70:
• Sex chromosome aneuploidies and
translocations are the most common
chromosomal abnormalities
14. In cases with
47,XXY or translocation,
PGD/prenatal diagnosis is offered
during genetic counseling
15. Azoospermia
Nonobstructive
Y microdeletion
The incidence of Y microdeletion
in non-obstructive azoospermia
patiens : 8-18 %
At least 15 gene families
involved in spermatogenesis are
located in Yq11.2 region
Before ART, Y chromosome microdeletions
should be screened in non-obstructive azoospermia
patients having normal karyotype
17. • During genetic counseling it should be
explained that the male offspring of the Y
microdeletion patients undergoing ART
will also have Y microdeletion.
• It has been reported that microdeletion
region may expand and may also occur
de-novo after ICSI procedure
Lee SH, Ahn SY, Lee KW, Kwack K, Jun HS, Cha KY. Intracytoplasmic sperm injection
may lead to Vertical transmission, expansion, and de novo occurrence of Y-chromosome
microdeletions in male fetuses.Fertil Steril. 2006 May;85(5):1512-5.
19. Other genetic disorders causing defective
spermatogenesis and/or functional disorders
• Myotonic dystrophy
• Noonan syndrome
• Kartagener syndrome
• Sickle cell disease
• Beta thalassemia
AR or AD
inheritance
20. Female Infertility
• Genetic reasons are less
• Major issues..
• Advanced age
• POF..Fragile X Carrier,X chromosome
abnormalities…To identify them..and offer a
good chance in that short window period is a
challenge
21. Chromosome X
abnormalities 45,X0
Kısa kol
kaybolur,
uzun kol
duplike
Olur
Isodicentric X
Triple X
45,X0/46,XX
Mosaic Turner
Premature ovarian
failure (POF)
22. Preimplantation Aneuploidy
Screening
• In the first studies chromosomes
13, 18, 21, X and Y were
screened
• Recently two subsequent FISH
have been applied for the
chromosomes 13, 18, 21, X, Y
13,16, 22, 14,15….
• Implantation rate did not
change
• The number of aneuplodic
fetuses decreased
Gianorolli L et al. 1997
• Implantation rate
increased two fold
• Pregnancy rate per cycle
increased
Munne S et al. 2005,
Platteau et al. 2005
In the groups of advanced maternal
age and multiple IVF failure
23. Aneuplodies in the arrested embryos
EÜTF: Dr. T. Çankaya , Dr. E. Tavmergen, Dr F. Özkınay (2003)
resultsThe number of anomalies
mean normal abnormal
Embryo no
25. Does the procedure used in infertility
treatment increase the risk of genetic
disorders in the child?
Controversial
1. Sex chromosomes abnormality frequency
•0.2- 0.5 % in population
•1 % in ICSI babies
2. The frequency of congenital abnormalities
increases two fold in ICSI babies.
Cardiovascular, urogenital, musculo-skeletal
J, Hansen M, Bower C: The current birth defects inchildren born after assisted
reproductive technologies.
Curr OpinObstet Gynecol 2004; 16: 201– 209.
Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk J: Assisted reproductive
technologies andthe risk of birth defects – asystematic review. Hum Reprod 2005; 20:
328– 338
26. Epigenetic factors
1. Before fertilization ,during gametogenesis
2. Certain paternal and maternal genes are
imprinted reversibly.
Paternal imprinting
Maternal imprinting
ART procedures may disturb genomic imprinting
mechanisms?
The risk of imprinting disorders increases.
e.g. Angelman, Prader Willi, Beckwith Wiedemann
27. What is Epigenetics?
• Epigenetics is the study of inherited changes in phenotype (appearance)
or gene expression caused by mechanisms other than changes in the
underlying DNA sequence.
• These changes may remain through cell divisions for the remainder of
the cell's life and may also last for multiple generations.
• Changes in gene expression that do not involve alterations in DNA base
sequence
33. - When histones are tagged, or acetylated, chromatin is open
and genes are potentially active;
- When histones are not chemically tagged, deacetylated, the
chromatin condenses and genes silenced.
Epigenetic Modification: Histone Modifications
34. DNA Methylation Influences Processes
DNA Repair
Hormonal
Regulation
Carcinogen
Metabolism
Apoptosis
Differentiation
Cell Cycle
DNA
Methylation
35. • DNA methylation and histone modifications, and chromatin remodeling,
such as repositioning of nucleosomes.
These heritable modifications are collectively termed “epigenetic codes”
(reviewed in Richards and Elgin, 2002).
37. Three significant developmental windows are likely to be
sensitive to exogenous signals that may alter epigenetic
profiles with impact on reproduction and fertility
1.Reprogramming of the germ line during PGC erasure‐
2.DNA methylation establishment during oocyte growth
and maturation
3.Reprogramming in first cell cycle – meiosis and mitosis
in transition
• These windows all involve dramatic changes in DNA
methylation
38. Developmental origins of adult disease
An adverse periconceptional and intrauterine
environment is associated with epigenetic
malprogramming of the fetal metabolism and
predisposition to chronic, in particular metabolic
disorders later in life (“Barker hypothesis”).
The epigenome appears is most plastic in the late
stages of oocyte and the early stages of embryo
development.
Suboptimal conditions during oocyte and embryo
development may lead to persistent changes in the
epigenome influencing disease susceptibilities later in
life.
Gluckman et al., Nat. Rev. Endocrinol. 5, 401-408, 2009 Lehnen et al., Mol.
Hum. Reprod., 2013
40. At present, the few available data in humans are
insufficient to allow us to independently determine the
impact of a woman's age and infertility problems and
treatment protocols and hormone doses on such
processes as genomic imprinting.
(Fertil Steril! 2013;99:616–23. !2013 by American Society for Reproductive medicine .)
41. Profound DNA methylation losses leave male and female
gametes hypomethylated at mitotic and meiotic arrest
42. Epidemiological data
• IVF children in Sweden (n = 31,850) 1 BWS, 2 SRS and 4
PWS
• Danish National Cohort study (n = 6,052) none with a
genomic imprinting disease
• French cohort IVF children (n = 15,162) 6 BWS
– cf. spontaneous BWS incidence 1/13,700
tendency towards ↑ risk after ART
43. Epigenetic aspects of ART in human
• irrespective of cause of
infertility
• after IVF and ICSI
• ET or FET on Day 2,3,5
• different stimulation
imprinting disorders in children born after ART
3.1~16.1
after IUI + COS or COS alone BWS reported
Not ART practice but subfertility is at the heart of this increase in BWS
Beckwith-Wiedemann syndrome
44. Angelman syndrome (AS)
• neuro-genetic disorder: characterized by intellectual and
developmental disability, sleep disturbance, seizures, jerky movements
(especially hand-flapping), frequent laughter or smiling, and usually a
happy demeanor
• Caused by a shortage of maternal UBE3A expression in the
SNRPN imprinting cluster
7 AS cases from ovulation
induction and/or IUI
45. Silver-Russell Syndrome (SRS)
• Dwarfism
• 5 cases published in children born after IVF or ICSI
– 1/5 hypermethylation of paternal MEST DMR
• Mechanism:
– ~ 44% of SRS caused by H19 DMR hypomethylation
– 5-10% by maternal uniparental disomy of Chr 7 So far, no imprinted
candidate gene on Chr 7 could be identified
46. Genomic imprinting
• DNA is methylated by epigenetic
mechanisms.
• Primary DNA sequence is intact
CpG island
• Reversible
inactivation
• Mutation Ø
47. Monozygous twins share a
common genotype and are
genetically identical
There is significant
phenotypic discordance:
Mental disorders
Cancer
48. • Both maternal and paternal genomic
materials are needed for normal fetal
development.
• Paternal genomic material:
Extraembrionic structures
• Maternal genomic material :
Fetal development
49. DNA Is Not Destiny …The new science of epigenetics
rewrites the rules of disease, heredity, and identity
Epigenetic inheritance is an essential mechanism that
allows the stable propagation of gene activity states from
one generation of cells to the next.
50. Artificial environment during ART procedures
may disturb the imprinting mechanisms in
gamets and imprinting disorders may occur in
the fetus
51. Clinical presentation
• ↑ risk of childhood cancer
• macroglossia
• macrosomia (birth weight and length > 90th percentile)
• midline abdominal wall defects
(omphalocele/exomphalos, umbilical hernia, diastasis
recti)
• ear creases or ear pits
• neonatal hypoglycemia
52. • Today a successful pregnancy is mainly
defined by the outcome at birth, however we
also have to consider the consequences of
ART conditions for later life.
53. Take home message
• ART can induce epigenetic variation that might be
transmitted to the next generation.
• Ovulation induction and in vitro culture..needs to
be revisited
• DMR methylation defects are associated with poor
spermatogenesis !!
• A multigenerational study of systematic ART on
epigenetic parameter is lacking.