Reproductive Ageing Flashcards
Why do women live longer?
Advantage of second X chromosome, compensating for defective genes
Generally having longer telomere length than men = potentially slowing cellular ageing and increasing lifespan
How does estrogen influence ageing?
Acts as antioxidants
Protects cells
Promotes DNA repair
May boost immune function
How does testosterone influence ageing?
Increases muscle mass and risk-taking
May suppress immunity and raise CVD risks
What happens when a male is castrated?
Loss of reproductive capability
Decrease in testosterone without changing the genetic information
(small amount of T produced by adrenal glands)
Why may males be castrated?
Cancer treatment (prostate and testicular)
Gender-affirming surgery
Castrati singers / Eunuchs
Sex Offender Rehabilitation
What is the impact of prepubertal castration on lifespan?
This remains undefined
What is the difference between fecundity and fertility?
Fecundity = potential biological ability to produce offspring
Fertility = number of offspring produced
What happened when fly food conc was increased?
Trade-off
Lifespan decreased
Fecundity increased
What happened when high mortality was imposed on fly population?
Flys tended to invest more resouces in egg production
What is the Disposable Soma Theory?
Trade-off between reproduction and somatic maintenance
Limited resources must be allocated to either
Production and protection of germ cell line for reproduction
Maintenance of the body, which functions as vessel to carry the germ cells
Define Darwinian fitness
Fertility x Survival
What does the Disposable Soma Theory say about Darwinian fitness?
Suggests it peaks at a balanced investment in repair
Enough to survive and reproduce, but no so much as to prevent ageing entirely
How does giving birth affect longevity?
Women who had children later in life are more likely to experience increased longevity
Increased number of children birther was associated with decreased lifespan
Describe the fertility in women vs men
Women born with finite number of oocytes that decline over time = significant decrease in quntitiy and quality after 35
Men begin producing sperm at puberty and maintain production throughout life with gradual declines around 45
What are the 5 hallmarks of male reproductive ageing?
Lower T levels
Reduced sperm production and quality
Decline in sexual function
Cellular ageing and oxidative stress
Reduced energy production
How is sperm quality affected as males age?
Sperm are less motile and have DNA damage
Cells produce less energy = affecting sperm movemet and health
What are the 3 phase for testosterone surge?
Fetal = genitalia development & brain masculinization
Neonatal = growth of reproductive organs & early brain development
Pubertal = development of secondary sexual characteristics
Increase in libido and sperm production
What is the axis that regualtes T?
Hypothalamic-pituitary-gonadal
How does HPG axis work?
GnRH = simulates ant pit to release LH and FSH
LH = simulates Leydig to release T
FSH = stimulates Sertoli to stimulates spermatogenesis working with T
Testis produce T = negative feedback to brain to maintain hormonal balance in spermatogenesis
How are GnRH frequency and amplitude affected by ageing?
Pulse frequency increases with ageing
Pulse amplitude decreases with ageing
Looks at GnRH promoter activity
How does T function in spermatogenesis?
Leydig cells release T to Sertoli cells
Stem cells become primary then secondary spermatocytes
Late spermatid and then spermatozoon
How does T target Sertoli cells?
T is a steroid hormone
It can diffuse across the lipid bilayer of Sertoli cell membranes due to its lipophilic, fat-soluble properties
What are Sertoli cells needed for?
“Nurse” cells for spermatogenesis
Needed for creating a nurturing env for germ cells
What regulates Sertoil cells?
Testosterone and androgen receptors
Where are andorgen receptors found and what do they do?
Nuclear receptors
Directly influences DNA transcription upon activation
How is testosterone’s action mediated?
Mediated through changes in gene transcription
Leads to long-term alterations in Sertoli cell function
Name the steps of androgen receptor activation
T is secreted from Leydig cells then transported to target tissues
T diffuses through plasma membrane
T converted to DHT by 5a-reductase
DHT binds to AR and promotes dissociation of HSPs from AR
AR translocates into nucleus and dimerizes
Dimerized AR binds to androgen response element (ARE) in promoter region of target genes
AR function as TF
What cardiovascular symptoms arise in T deficiency in men?
Higher risk of hypertension, dyslipidemia, atherosclerosis
Decrease in HDL cholesterol
What psychological symptoms arise in T deficiency in men?
Mood swings, anxiety, and depression
Cognitive decline = memory & processing speed
What metabolic symptoms arise in T deficiency in men?
Increased body fat
Decreased muscle mass
Decreased bone density
What general symptoms appear in men with testosterone deficiency?
Fatigue/reduced stamina
Weakened immune function
What physical symptoms occur in men with T deficiency?
Thinning skin
Reduced body & facial hair
What effect does low T levels have on mortality risk in men?
Low T levels = high mortality risk in men
What is testosterone deficiency known as?
Hypogonadism
What are the possible treatments for male hypogonadism?
Transdermal delivery
Intramuscular/subcutaneous delivery
Oral delivery
What does metformin do?
Activates AMPK
Enhance mitochondrial function
Reduce inflammation
Promote metabolic health
What does rapamycin do?
Inhibits mTORC to
Promote autophagy
Reduce cell senescence
Enhance stress resistance
How did in vivo Metformin treatment effect male rat sperm?
May benefit male reproductive health in cases of obesity
But appears to have negative effects in normal conditions
How does rapamycin affect male reproductive health?
Inhibition of mTORC impairs male reproductive health
