Reproduction, Development and Ageing Flashcards
What are the male reproductive hormones?
- gonadotrophin releasing hormone (GnRH) - hypothalamus
- luteinising hormone (LH) - anterior pituitary
- follicle stimulating hormone (FSH) - anterior pituitary
- testosterone - testis
What are the reproductive hormone names based off?
o there action in FEMALES
- in the testes there are no follicles -> LH and FSH names have nothing to do with their action biologically or physiologically in males
What is the course of ejaculate?
- sperm are released from the testis and stored within the epididymis within the scrotum prior to ejaculation
- at ejaculation sperm pass through the two Vas Deferens (which are contractile), and is mixed with fluid from the seminal vesicles -> the fluid then leaves the ejaculatory duct, and passes into the urethra where it mixes with secretions from the prostate gland
- then is contiunally propelled out of the urethra
Describe Leydig cells.
- lie outside of the seminiferous tubules
- the primary source of androgens in ALL male mammals -> prodominantly testosterone
- site of LH action
Describe Sertoli cells.
- cells in the seminiferous tubules support the process of spermatogenesis
- produce inhibin
- function of Sertoli cells is driven by FSH and testosterone together
Describe the production of testosterone.
- produced in the testis by Leydig cells
- inhibin negatively feeds back on the hypothalamus to constrain the production of GnRH
- testosterone also feeds back from the Leydig cells to the hypothalamus and pituitary gland -> therefore constrains the production of gonadotrophins (LH/FSH)
- androgen binding protein mediates the effects of testosterone on Sertoli cells by binding to testosterone
- is a pulsatile manner to the regulation of the productive system
Where are sperm produced?
- seminiferous tubules
Describe spermatogenesis.
- primordial sperm cells undergo mitosis to produce prmary spermatocytes
- primary spermatocytes undergo the first stage of meiosis to produce secondary spermatocytes -> the second meiotic division produces spermatids
- spermatids then mature into spermatozoa
Do men go produce sperm throughout their lives?
o yes, after puberty
- quantity and quality does generally decrease with increasing age
What are the females reproductive hormones?
- gonadotrophin releasing hormone (GnRH) - hypothalamus
- luteinising hormone (LH) - anterior pituitary
- follicle stimulating hormone (FSH) - anterior pituitary
- oestrogen - ovaries
- progesterone - ovaries
Describe the reproductive axis in women in the follicular phase.
- hypothalamus prodcued GnRH which stimulates the anterior pituitary to prodcue and secrete FSH and LH
- this causes the ovary to produce estradiol and progesterone -> oestradiol is dominant
- oestradiol then has a negative feedback on the hypothalamus and the pituitary
- around 10 days in oestradiol switches to positive feedback on the hyothalamus and pituitary which causes a LH surge which further drives the positive feedback -> oestradiol is still dominant
Describe the reproductive axis in women in the luteal phase.
- after ovulation the cycle switches back to negative feedback on the hypothalamus and pituitary
- progesterone aslo becomes dominant to maintain the uterine wall
What occurs to the female hypothalamus-pituitary axis in pregnancy?
- progesterone levels RISE, and continues to do so for the whole length of pregnancy -> switches off the whole hypothalamic-pituitary axis
- menstrual cycle completely comes to a halt during pregnancy due to progesterone –ve feedback
Which phase of the ovarian cycle will change its length if the cycle becomes shorter or longer due to environmental factors?
- the luteal phase -> stress can make this phase several days longer
What physiological change occurs at ovulation?
- a womens body temperature will rise by around 0.5 degrees celcius
Describe the endometrial cycle.
Describe oogenesis.
o the first polar body is essentially a nucleus -> takes half of the chromosomes away -> process comes to a halt at the point of the development of the secondary oocyte -> eggs are metaphase II
- meiosis resumes at the point of puberty, and after that point -> individual eggs resume the process as they go through the final stages of folliculogenesis
- the longer the eggs are held, the poorer the organisation of the DNA -> why developmental problems are associated with increasing maternal age
o start with a primary oocyte, living inside a primordial follicle -> follicle starts growing independent of the sex hormones
o eventually, one follicle becomes dominant -> grows more quickly than the others -> dominant follicle enters the secondary part of the development, to become the antral follicle
o antral follicle gives rise to the egg that is released -> other follicles enter the process of atresia and break down -> normally, one ovary produces one dominant follicle per cycle (not always the case)
How long does the process of producting a mature oocyte take?
- around 3 months
- will be multiple occytesmaturing in each ovary
How long can oocytes and spermatozoa last in the femlae reproductive tract?
- oocyte = 24 hours
- spermatozoa = 3 days
Describe fertilsation.
- sperm swims to where the egg is in the fallopian tube -> once close enough are attracted by chemo-attraction
- binds to the zona pellucida on the outside of the egg -> sperm produce digestive enzymes to digest their way through the zona pellucida -> eventually, one sperm will RELEASE its nucleus into the cytoplasm of the egg
- meiosis of maternal chromosomes resumes, forming female pro-nucleus (23 chromatids), and the second polar body
- sperm chromosomes de-condense to form male pro-nucleus (23 chromatids)
- BOTH pro-nuclei are duplicated and then align on the mitotic spindle, and are separated into 2 identical ‘daughter’ cells -> done at the 1st cleavage division of the embryo
What cause penile and clitoral erection?
- partly under the control of the brain, via the spinal cord and efferent nervous system
- tactile stimulus of the organ can activate the afferent system (pudendal nerve) -> is a more direct interaction
What changes occur during erection?
- initiated by increased parasympathetic activity to smooth muscle of pudendal artery
- is an increases in the activity of Nitric Oxide Synthase (NOS), and hence nitric oxide (NO) -> increased production of cyclic GMP which induces dilatation of arterial smooth muscle -> increases blood flow in corpus cavernosum
- in turn this compresses the dorsal vein, restricting the outflow of blood
- urethra is protected from increased pressure by surrounding corpus spongiosum (less turgid)
- same mechanims are in play in the clitoris
When is the absolutel limit of survival outside of the womb?
- without the intensive care unit, the absolute limit of survival outside the womb is 27 weeks (defines the end of the second trimester)
- modern intensive care cots have increased this limit to 23 weeks -> is extremely dangerous -> survival rates are quite low when premature births take place
What are the maternal changes that occur during pregnancy and what trimester do they prodominantly occur in?
- increased weight [3rd]
- increased blood volume [2nd & later]
- increased blood clotting tendency [2nd & later]
- decreased blood pressure [2nd]
- altered brain function [throughout] – function of the brain changes
- altered hormones [throughout] – can be largely different to normal physiology
- altered appetite (quantity and quality of what the mother eats changes) [throughout]
- GI imbalance (morning sickness)
- altered fluid balance [2nd & later]
- altered emotional state [throughout]
- altered joints - e.g. more flexible knees [3rd]
- altered immune system [throughout]
What hormonal changes occur in a women during pregnancy?
- human chorionic gonadotrophin is the key hormone in early pregnancy -> is a functional homologue of LH, driving the production of oestrogens and progesterones from the corpus luteum
- corpus luteum usually degenerates towards the end of the last week of the menstrual cycle -> fall in progesterone results in the breakdown of endometrium -> to keep the pregnancy going, we need progesterone -> hCG drives the progesterone production from the corpus luteum -> peaks and falls in the first trimester
- placental lactogen is produced, and levels increase as the size of the placenta increases, same pattern of production is seen in progesterone and oestrogens
- by 10 weeks gestation, the placenta is the source of all progesterone -> up to then, mainly corpus luteum
- levels of progesterone and oestrogens greatly exceed the levels seen during the normal menstrual cycle, so they may have potent effects on the maternal system in pregnancy -> are well above required because low progesterone levels lead to loss of the pregnancy at all gestational ages.
- high levels of steroids suppressing the HPG, leads to very low levels of LH and FSH throughout pregnancy, and hence no cyclic ovarian or uterine functions
What is meant by the term conceptus?
- everything resulting from fertilised egg -> baby, placenta, fetal membranes, umbilical cord
What are the timing issues in pregnancy?
- menstrual cycle is not precisely 28 days, and ovulation is not precisely on day 14
o first day of the last menstrual period is taken as the start of pregnancy -> a clearly established day -> from this, we can work out when the women ovulated (2 weeks after that)
o embryologists, however, will take the first day as being the point of fertilisation
- these timings differ by 2 weeks -> doesn’t make a huge difference in the scheme of ‘term dates’ but does at the beginning of pregnancy
What are the lumps in a placenta called?
- cotyledons
Describe the structure of the placenta.
- placental villus is extensively branched, which provides a very large surface area
- maternal vascular system is set up over this surface area
- umbilical vein carries the oxygenated blood (is flowing away from the foetal heart) and the 2 umbilical arteies carry the deoxygenated blood -> same as in the lungs
What are the functions of the placenta?
- separation of blood supplies of mother and baby
- exchange of nutrients (maternal to foetal) and waste products (foetal to maternal)
- connection (or anchorage)
- immunoregulation -> allows the maternal immune system to switch off
- biosynthesis -> e.g. progesterone, oestrogens and hCG
Describe the development of a placenta.
- starts as a layer of single cells in the blastocyst
- day 9 post-fertilisation, the conceptus is almost completely implanted within the endometrium -> At this stage, the outer layer of the conceptus is multi-nucleated syncytiotrophoblasts containing fluid-filled lacunae
- underlying layer of cytotrophoblast is proliferating adjacent to the embryo -> where the placenta will develop -> following implantation, the cytotrophoblast proliferate into the syncytium
- a columnar structure forms (cytotrophoblast column), which undergoes branching (villous sprouts) -> at the centre of each villus are mesenchymal (extra-embryonic mesoderm) cells -> from these cells, the villus vascular system develops
- branching continues throughout pregnancy -> gives rise to the complex branched villi
Why do cytotrophoblast shells limit blood supply to an embryo in early development?
- keeps the number of free radicals from oxygen low -> less likely to cause damage
- allows for remodelling of spiral arteries to allow high volume of blood in second and third trimesters
What does mal-development of the placenta lead to?
- miscarriage (late first trimester) – if the placenta doesn’t anchor properly
- miscarriage (second trimester)
- pre-eclampsia (early delivery)
- fetal growth restriction (small infant)
What is the cut off point for a delivery to be considered term?
- term = 37-41 weeks
- pre-term = 23-37 weeks -> mostly due to pre-term labour but some are due to C-sections due to a significant risk to the baby and/or mother
Define labour.
- fundally dominant contractions, coupled with cervical ripening (softening) and effacement (thinning of the cervix as well as expanding sideays)
Describe the process of labour is independent of gestational age.
- cervical ripening and effacement (increasing)
- co-ordinated myometrial contractions (increasing)
- rupture of fetal membranes
- delivery of infant
- delivery of placenta
- contraction of uterus
What are Braxton Hicks contractions?
- a latent stage, around 8 weeks before labour, in which the myometrium undergoes changes
- rather than being completely relaxed (to allow for foetal growth), a part of it contracts briefly, and relaxes
- occurs intermittently but regularly
Describe phase I of labour?
- involves contractions and cervical/uterine changes
- > contractions become more powerful and more co-ordinated
- > cervix begins to soften (ripening) and gets thinner (effacement)
- length of phase I is incredibly variable (12 to 48 hours) -> gets shorter with subsequent pregnancies
Describe phase II of labour.
- baby is delivered
- > contractions continually get stronger and more frequent
- can last hours but is never as long as phase one
Describe phase III of labour.
- the placenta is delivered
- around half an hour long
What initiates term labour?
- no-one really knows
- might be driven by oestrogens, low progesterones, CRH and oxytocin etc
What initiates pre-term labour?
- intrauterine infection
- infection elsewhere in mother’s body
- intrauterine bleeding
- multiple pregnancy
- maternal stress
- many other factors
Describe cervical ripening and effacement.
- change from rigid to flexible structure
- remodelling (loss) of extracellular matrix
- recruitment of leukocytes (neutrophils)
o is an inflammatory process -> leads to the production of:
- > prostaglandin E2, interleukin-8
- > local (paracrine) change in IL-8
Describe co-ordinated myometrial contractions.
- fundal dominance
- increased co-ordination and power of contractions
- mediated by:
- > prostaglandin F2a (E2) levels increased from fetal membranes
- > oxytocin receptor increases -> more oxytocin receptors (not oxytocin) means the uterus in more responsive to it
- > contraction associated proteins
Describe rupture of the foetal membranes.
- loss of strength due to changes in amnion basement component
o is what is happening when a woman’s ‘water breaks’
- involves inflammatory changes and leukocyte recruitment -> is modest in normal labour, exacerbated in pre-term labour
- > increased levels and activity of MMPs
Which pro-inflammatory transcription factor is most important in labour?
o NF-Kappa-B
- enters the nucleus and upregulates lots of porteins which are key in labour -> e.g. COX-2 (prostaglandins), IL-8, IL-1b, MMPs, oxytocin receptor, PG receptors, contraction-associated proteins
Name the current top 2 factors for initiating normal labour.
- corticotrophin releasing hormone
- platelet activating factor
Why does CRH make sense to be an initiator of labour?
- its maternal blood circulation levels rise dramatically in the last 3-4 weeks of pregnancy due to the loss of its binding protein
- it increases the production of prostaglandins (COX-2, E2) which are known to be important in labour
Why does platelt activating factor make sense to be an initiator of labour?
- PAF is part of lung surfactant
- babies don’t have surfactant in utero however surfactant proteins and complexes are produced in the last couple of months of pregnancy by the maturing lungs -> more mature the lung is = the higher the levels of surfactant get
- levels of surfactant in amniotic fluid increase near term -> a foetal signal of maturity -> baby can now be delivered safely, because it can breathe air
What is the current hypothesis on parturition?
- high levels of CRH will start to switch UP IL and prostaglandin production in the foetal membranes
- cortisol from the adrenal gland is acts on the foetal lung -> stimulates the foetal lungs to produce surfactant (including PAF)
o high levels of cortisol production = more surfactant produced = more PAF
- lungs are in intimate contact with amniotic fluid (baby takes amniotic fluid into lungs, and expels it) -> allows PAF to enter the amniotic fluid, and PAF upregulates the same factors in the membranes
What is DHEAS?
- a steroid produced in the adrenal glands
- can move to the placenta and can be converted to oestrogens
- oestrogens upregulate PGs, OT and OT receptors -> all required for increased myometrial contractility
How does pregnancy occur despite progesterone levels remaining high?
- progesterone is NEEDED to sustain pregnancy -> one of the ways of causing pregnancy loss is giving a progesterone antagonist
- progesterone levels remain very high until after delivery of the placenta (unlike sheep) but the effect of progesterone is lost in normal term labour -> thought to be because there is an interaction between the progesterone receptor and NFkB
- throughout pregnancy progesterone receptors are present in large quantities (unlike NFkB) therefore, NFkB cannot do its normal job of upregulation inflammatory cascades
- at the end of pregnancy, NFkB levels rise (driven by CRH/PAF) and progesterone levels fall
- switching off of progesterone may act as an initiator of labour
Define foetal growth.
- increase in mass that occurs between the end of embryonic peoid and birth
What 2 factors is foetal growth dependent on?
o genetic potential -> derived from both parents and mediated through growth factors e.g. insulin like growth factors
o substrate supply -> essential to achieve genetic potential
-> derived from placenta which is dependent upon both uterine and placental vascularity
What are the 3 phases of normla foetal growth?
- cellular hyperplasia (happens rapidly in the first few weeks)
- hyperplasia and hypertrophy
- hypertrophy alone
What techniques are used to ante-natally asses the size of a foetus?
- palpation of the maternal abdomen
- measure the uterus with a tape measure -> measure their symphysis fundal height = pubic symphysis to the fundus of the uterus - SFH
Why might a foetus be measured to be smaller than expected?
- we have the wrong dates
- baby is small for gestational age -> could be pathological or just a small baby
- oligohydramnios - amniotic fluid deficiency
- the foetus is lying transversely
Why might a foetus by measured to be larger than expected?
- we have the dates wrong
- molar pregnancy
- multiple gestation
- large for gestational age
- polyhydramnios - excess amniotic fluid
- maternal obesity
- fibroids - non-cancerous growth of the uterus
What are the pros and cons of SFH?
o pros of SFH = SIMPLE and INEXPENSIVE
o cons of SFH = low detection rate, great inter-operator variability, influenced by a number of factors (BMI, foetal lie, amniotic fluid, fibroids)
- nowadays, in modern obstetric practice, we use ultrasound machines to measure the baby more objectively
How are pregnancies dated?
- dating can be done by asking the mother for the first day of her last menstrual cycle (LMP) -> fairly inaccurate method (irregular periods, abnormal bleeding, contraceptives, breast feeding)
- nowadays all pregnancies are dated using the crown rump length (CRL) -> exception being IVF (know exactly when the embryos were made)
What 4 measuremenst are taken to asses foetal growth?
- bi-parietal diameter
- head circumference
- abdominal circumference
- femur length
What are the factors that influence foetal growth?
o maternal factors -> poverty, age, drug use, weight (low BMI can result in a small baby), disease (hypertension, diabetes, coagulopathy), smoking, alcohol, diet, prenatal depression, environmental toxins
- foeto-placental factors -> genotype -> genetic potential, gender (B>G), hormones -> previous pregnancy (if a mother has had a previously affected pregnancy with intra-uterine growth restriction, she is at a higher risk of having it again in subsequent pregnancy)
What is the consequences of impedence of the umbilical veins?
- foetus moves less to reserve energy
How does sonic hedehog gene influence growth of the limbs?
- expressed in the control centre of the limbs -> co-ordinated the development of the limbs
- if it is also expressed on the corresponding mirror image you will get the formation of a limb which is symmetrical -> 2 thumbs and 2 fingers (in a chicken a wing with two end bones)
What are the 3 types of spina bifida?
- spina bifida occulta -> CNS is okay but the spine isn’t correctly formed -> characterised by a small patch of hair over the lesion -> is hidden and often doesnt cause any major problems
- meningocele -> a swelling/lesion containing CSF pokes out of the spinal column
- myelomeningocele -> swelling/lesion containing nervous tissue pokes out of the spinal column -> all nerves below the lesion will be damaged and many will not function at all
Describe the development of the spinal column and what goes wrong in spina bifida?
- development of the bony part of the spine is driven and controlled by neural tissue (CNS tissue)
- spina bifida development takes place within the first 4 weeks post-fertilisation
- formation of the CNS is the formation of a tubular structure
- in spina bifida, the tube does not completely seal up (in one or more places) -> this process is called neuralation -> in spina bifida, neuralation is of the posterior neuropore is faulty
What is the height velocity calculation?
Describe the 5 stages of puberty.
- stage 1 = hormone production begins/increases but there aren’t any physical signs
- stage 2 = change in body shape (breast begins to form, more triangular in boys and curvy in girls) and pubic hair begins to appear -> girls begine to grow in height and weight
- stage 3 = contiuation of growth and change in body shape (boys also begin to grow) as well as changes in siza and shape of genitals -> boys shoulders and muscle mass increases dramatically and voice begins to deepen
- stage 4 -> girls = breasts and aureolas develop, pubic hair has a more triangular adult appearance, menarche will begin if it hasn’t already
- > boys = penis starts to grow in width (texture more adult like too) , testicles and scrotum also continue to grow, hair may begin to grow on the anus, armpits and face, the voice continues to deepen
- stage 5 = final height is reached/approached, genital and hair is like that of an adults = fully developed -> some boys will continue to grow into their 20s
How does frailty develop?
- genetic factors -> some people age faster than other people -> if your parents live to old age, you are much more likely to live to old age
- environmental factors (e.g. smoking and alcohol consumption) -> combine to cause cellular and molecular damage -> reduced physiological reserves in all the organ systems -> FRAILTY
- a minor stressor event pushes people beyond their functional reserve -> cannot cope anymore -> this often becomes cyclical
What are the differences between dementia and delirium?
