Developmental aspects and programming of reproduction Flashcards
LO
- Why we need to be aware of developmental programming of reproduction
- Critical stages in the fetal development of the reproductive system during gestation
- Environmental factors that influence the development of the reproductive system, and their consequences on adult offspring reproductive function
Why is reproduction important?
- It is the only way for a living being to continue its lineage
- Without the means of making more individuals, a species wouldn’t be able to proliferate or survive from generation to generation
- Reproduction facilitates evolution because variations come through reproduction over several generations
Tell me about the levels of declining fertilities worldwide
- Infertility affects at least 20-25% of couples who are of reproductive age
- Around 35% of men are sub-fertile and at least 2% of men are total infertile
This is an example of declining fertility in Japan
What are the causes for the decline in fertility?
- Urbanisation and high housing cost
- Female literacy
- Increased knowledge and understanding of contraception
- Later marriage- more females stay on in school and in high education; and
- Later childbirth and fewer births are more worm pursue careers
- Abortion
- Diseases
- Infertility- detrimental early life environment
What are the stages to the male reproductive system?
What are the stages to the female reproductive system?
What system plays a key role in reproduction?
The endocrine system
What aspects of the endocrine system are important for reproduciton
- Pituitary is most important gland in this system in males and female system
- Gland axis is when gland communicate in sequence
- HPG axis; The hypothalamic-pituitary-gonadal axis
Tell me the key factors which are involved in the development of sexual phenotypes in mammals (the genetic aspects of sexual differentiation)
- gonad formation is chromosomal
- Not usually influenced by environment (apart from in some reptiles and fish where temp. can determine gender)
- 22 pairs of autosomes and a pair of sex chromosomes
- TDF mapped in short arm of Y-chromosome. And found in SRY gene (Sex-determining region of Y). This gene determines whether gonad develops into male or female structure
Whats the Gestation period timeline?
Tell me about the different stages of development of sexual phenotypes in mammals (differentiation of the gonads)
How do the male and female karyotypes form?
- primary sex organ is the gonads (testes in males and ovaries in females)
- In bilateral swelling of embryo development is when the gonads develop. This is called the gonadal ridge
- Ridge which is adjacent to kidney
- Germ cells give rise to gametes. Play a key role in sexual differentiation. These effects gonadal development in this ridge
- Germ cells migrate to gonad from yolk sac at around 5 weeks
- Primordial germ cells actively migrate to gonadal ridge. This ridge is comprised of outer cortex and medulla
- This ridge has the capacity to develop into either gonad
- Genotype of embryo (determined by SRY)
- In males (XY Karyotype):
- The cells then migrate to primitive sex cord in medulla and induces maturation of sex cord structure which develops into seminiferous tubules. Which houses Sertoli cells and produces MIS/ anti-Mullerian hormone.
- This hormone plays a further role in development
- The primordial germ cell gives rise to spermatogonia (first cells in pathway to mature sperm). Sperm cell takes residence in sex cord
- Leydig cells at 10 weeks these cells start to produce testosterone
- In females (XX Karyotype):
- Becomes female gonad
- The medulla regresses and the primary sex cord is reabsorbed (unlike in male where it becomes seminiferous tubule)
- The cortex increases in thickness, and this is because of rise on progenitor cells, and this gives rise to the development of oogonia
- Oogonia are immature cells that give rise to primary oocytes
- At 8 weeks, the developing ovaries contains 6000 oogonia. By 20 weeks this rises to around 7 million
- After oogonia is diced off and reabsorbed, the remaining ones then become the primordial follicles which then becomes the primary eggs/ oocytes
- Around puberty there’s 3000 oocytes and only around 500 will mature over a lifetime
Tell me about the development of the internal genitalia is men and women and what are the key hormones involved in this?
There’s two ducts involved (wolffian and Mullerian duct): the organ is initially bipotential i.e., male or female reproductive structure
Initially Sertoli cells produce anti-Mullerian hormone and the Leydig cells produce testosterone
Secretion dictates the future of bipotential duct system
Male development:
Mullerian-inhibiting substance or Anti-Mullerian hormone (Sertoli cells)
Testosterone (Leydig cells)
Insulin-like factor 3 (Leydig cells)
Female development:
Absence of testosterone and AIS/AMH
Wolffian duct (male and forms vas deferens)
Mullerian duct (female and forms oviduct)
Whats the role of testosterone in development?
- Masculinisation of wolffian duct
- Develops in epididymis
- Forms Vas deferens
- Forms Seminal vesicles
- Forms Ejaculatory ducts
- Causes Urethra –> prostate gland
Whats the role of the anti-mullerian hormone in development?
- Facilitates the Mullerian duct degeneration
- Arrested development of structures forming female structures
What occurs in mammalian males to allow sperm to be cooled at a cooler temperature?
In most mammals, the male gonad does not remain in perirenal area like the ovary but instead undergoes migration into extra abdominal located called scrotum
Allows sperm to be stored at cooler temp
In females, the absence of testosterone and anti-Mullerian hormone causes what?
- Causes degeneration of Wolffian duct
- Mullerian duct grows
- This develops into fallopian tube
- Mullerian duct, the mid portion fuses and gives rise to uterus and the distal part forms the cervix and vagina
The plasma testosterone levels at various ages in human males
What causes the undifferentiated rodent brain to form the male and female brain?
The undifferentiated brain is basically female (the default structure)
Foetal testosterones transform the brain in the male structure via oestradiol (brain differentiation is dependent on the presence/ absence of oestrogen)
The transformation is governed by aromatase which is limited the production of oestradiol
What is meant by a male and female brain and what evidence has there been to support this?
What’s meant by a male or female brain structure?
- The pre-optic area. The size of this structure is different between males and female
In male its increased and smaller in females
This has been shown to be involved in male copulatory behaviour
In humans, this has been suggested to be involved in aggressive behaviour
What is some further evidence that has been found in humans which has been identified between male and female brains?
histological examination of male and female brain shows the sexually dimorphic nucleus is also different between the two genders
This nucleus is larger and more densely populated in cells in males compared to females
Foetal testosterone predicts sexually differentiated childhood behaviour in girls and in boys. Tell me an experiment that was done to explore this and what was determined from this
Girls that have prenatal testosterone exposure, caused by congenital adrenal hyperplasia (CAH), displayed more male-typical toy choices compared to unaffected girls
Boys with and without CAH did not differ in their male-typical toy choices
CAH refers to a group of genetic disorders that affect the adrenal glands. These glands produce hormones like cortisol which are important in regulating the bodies response to illness or stress
CAH is an inherited condition. There’s decreasing cortisol and an increase in male sex hormone especially testosterone. there’s a swelling of the adrenal gland
Tell me about the Transgenerational effects seen in rodents and what does this mean?
Transgenerational effects (TGE) can modify phenotypes of offspring generations playing thus a potentially important role in ecology and evolution of many plant species. These effects have been studied mostly across generations of sexually reproducing species.
- exposure to environmental factors during prenatal development causes multigenerational effects in the F1 and F2 generations and transgenerational effects in the F3 generation
- The F1 and F2 generations are directly exposed to the environmental factors as a foetus and germ cell, respectfully. The F3 generation is not directly exposed and the mechanisms governing the effects in the F3 generation are thought to be epigenetic in nature
- Direct effect on F1 and indirect effects on F2
- Transgenerational effect: Germ line is not directly exposed, an indirect exposed
What evidence has been found in humans in regard to the maternal/ foetal nutrition?
- Maternal obesity is associated with younger menarchael age amount daughters
- Menarcheal age= first period
Papers on the effects of a maternal low protein diet
What evidence has been found for maternal stress during pregnancy?
Lordosis behaviour: posture for sexual activity
This behaviour occurs in the female
The earlier testosterone surge of offspring who’s mothers were under stress may be earlier and can effect development of male brain
What evidence in humans has been found for maternal stress during pregnancy?
Stress in early (1st trimester), but not late (3rd trimester), pregnancy is associated with lowered sperm count and lower blood testosterone in males
Tell me about the potency of the environmental agents
- Persistent and stable in the environment
- Lipophilic resulting in bioaccumulation in body fat
- Synergistic effects
- Can induce ‘non-monotonic dose-response curves of biological effects’
What does in utero exposure to the environmental agents BPA A DES alter?
Sexual maturity and oestrous cycle of the female rat offspring
What does in utero exposure to the environmental agents BPA, DEHP and DBP induce?
In utero exposure to the environmental agents BPA, DEHP and DBP induce trans generation inheritance of reproductive diseases in male and female rat offspring
What does in utero exposed to DES alter?
In utero exposed to DES alters the size of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in the female rat brain
Trans generation effects of Vinclozolin (a fungicide) treatment to F0 pregnancy rat dams in subsequence generation of male offspring
Trans generation effect of environment toxicants treatment to F0 pregnancy rat dams on subsequence generations of female offspring
What evidence has their been in humans in regard to man-made chemicals?
What are the ffects of maternal smoking during pregnancy?
Maternal cigarette smoke exposure reduces adult male offspring sperm quantity and quality in mice
Ovarian lipid peroxidation and mitochondrial biogenesis
Proposed effects of obesogenic maternal diet on intracellular pathways in the ovary
What are the different epigenetic mechanisms?
- DNA methylation: Hypo- or hypermethylation
- Histone modification: repressive marks or active marks
- Non-coding RNAs; could involve gene silencing
Altered DNA methylation pattern of Peg3 in spermatozoa in male mouse offspring from high fat diet fed obese mothers
Altered DNA methylation regions (DMR) in sperm DNA from the F3 generation plastic lineage compared to control lineage
Vinclozolin-induced alteration in DNA methylation regions (DMR) in granulosa cells in ovaries from the F3 generation compared to control lineage
Tell me about the impacts of prenatal insults in programming adult reproductive pathologies in the offspring and the potential mechanissm
The cited papers
