SUGER: Reproduction Flashcards
Human eggs (ova) are small, develop slowly, and the female reproductive system is adapted to provide an environment for fertilisation and prolonged gestation, followed by parturition (birthing of live young).
What term describes this reproductive system?
Viviparous
What do primordial germ cells develop from?
Pluripotent cells (stem cells)
What are primordial germ cells?
Early precursors of gametes (spermatozoa/ova).
Epigenetics describes heritable changes in gene expression (gene turned on/off) that occur without alterations to the DNA sequence itself, influenced by factors like environment and lifestyle.
Give an example of an epigenetics mechanism of gene expression.
DNA methylation: methyl groups are added to DNA, blocking transcription from occuring.
Pluripotent (stem) cells have a distinct epigenetic pattern compared with non-pluripotent (differentiated) cells.
When does the change between pluripotent epigenetic pattern and the gametes epigenetic pattern occur?
During gametogenesis.
Parental imprinting occurs during gametogenesis, where epigenetic modifications (usually methyl groups) are placed in a sex-specific manner.
How does parental imprinting ensure monoallelic expression?
Parental imprinting means only one allele will be expressed in the child (monoallelic expression) because certain genes are always silenced in the egg, and others in the sperm. These are then again reset in gametogenesis in the offspring, depending on the sex of the offspring.
Briefly describe the HPG (hypothalamic-pituitary-gonadal) axis.
HYPOTHALAMUS releases gonadotropin-releasing hormone (GnRH).
GnRH stimulates the PITUITARY gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
LH and FSH act on the GONADS.
FSH is released from the pituitary gland in response to GnRH (gonadotropin-releasing hormone).
What effect does FSH have in males and females?
Stimulates sperm production in males (acts on sertoli cells) and follicle development in females.
LH is released from the pituitary gland in response to GnRH (gonadotropin-releasing hormone).
What effect does LH have in males and females?
Stimulates testosterone production (acts on Leydig cells) in males and ovulation in females.
What are the two key functions of the gonads?
Produce gametes and synthesise sex steroid hormones.
How do cells synthesise oestrogens (as a category of steroid hormone)?
Enzymes convert androgens (e.g. testosterone) into oestrogens.
How do cells synthesise androgens such as testosterone?
Through enzymatic reactions, usually from progestagens such as progesterone, which are originally synthesised from cholesterol.
Mesonephric (wolffian) ducts are the embryonic precursors to what structures?
Vas deferens, epididymis and seminal vesicle
In the ovary, when do the first follicles start growing?
During foetal development
Which hormone acts on Sertoli cells of the seminferous tubules to enhance spermatogenesis?
FSH
What provides the main source of oestrogens throughout pregnancy?
Placenta
During pregnancy, heart rate and stroke volume increase, causing cardiac output to increase by what %?
30-50%
When do primordial germ cells stop proliferating and enter meiosis, then becoming oocytes individually encapsulated by somatic cells (the primordial follicle)?
During foetal development.
When does a female have the most number of oocytes?
During foetal development (at 20 weeks post-conception)
How does the oocyte obtain nutrients within the zona pellucida in preantral follicles (primary/secondary)?
Through gap junctions at the end of transzonal processes (cytoplasmic projections that cross the zona pellucida) from granulosa cells.
What cells in the antral follicle have LH receptors, and are stimulated by LH to produce androgens?
Theca interna cells
What cells in the antral follicle have FSH receptors and are stimulated by FSH to convert androgens into oestrogens?
Mural granulosa cells (the granulosa cells towards the periphery of the follicle).
What effect do androgens from the theca interna cells in the antral follicle have on mural granulosa cells?
Along with FSH, they stimulate proliferation of mural granulosa cells (and also provide substrate for oestrogen production).
Explain the positive feedback mechanism involved in oestrogen production from mural granulosa cells in the developing antral follicle.
Oestrogens from mural granulosa cells stimulates mural granulosa cell proliferation (which is already stimulated by FSH and androgens from theca interna cells).
More mural granulosa cells = more cells which can produce oestrogen = major increase in oestrogen output as follicle develops.
What do high levels of FSH and oestrogen eventually cause in mural granulosa cells in the preovulatory/large antral follicle?
Stimulate expression of LH receptors.
What effect does rising oestradiol and inhibin release have on the pituitary gland during the preovulatory phase?
Inhibits FSH, stimulates LH secretion.
In the preovulatory follicle, what positive feedback mechanism is managed by granulosa cells in response to LH release from the pituitary?
Stop converting androgens to oestrogens and instead produce progesterone (essential for ovulation).
Also begin expressing progesterone receptors, and this amplifies the production of progesterone.
What important process does LH cause in the oocyte just prior to ovulation?
Breakdown of germinal vesicle (nucleus) of oocyte, causing oocyte to progress through meiosis and then arrest in metaphase II until fertilisation.
When do oocytes arrest in prophase I of meiosis?
During foetal development, when they are forming primordial follicles.
What is the thinnest point of the follicle called, where it bulges from the ovarian surface just prior to ovulation?
The stigma
What cells support the oocyte during ovulation?
Cumulus granulosa cells (part of the cumulus oocyte complex that enters ovarian tube).
What does the follicle become after ovulation, with the purpose of continuing to produce hormones (mainly progesterone) to maintain a uterine environment that allows for implantation and pregnancy?
Corpus luteum
Sympathetic fibres of what nerves generally depress erection?
Hypogastric nerves
Parasympathetic fibres and somatic fibres from what two nerves promote erection?
Parasympathetic = pelvic nerves
Somatic = pudendal nerve
What effect does parasympathetic stimulation of the penis have to cause erection? (4 steps)
- increases acetylcholine release
- this activates nitric oxide synthase to produce nitric oxide
- nitric oxide increases cyclic GMP (cGMP) (causing calcium depletion)
- which causes smooth muscle relaxation and therefore vasodilation
What occurs in normal physiology to prevent retrograde ejaculation?
Constriction of internal bladder sphincter.
How do vaginal secretions during sexual arousal increase likelihood of pregnancy?
Vaginal secretions released during sexual arousal are rich in HCO3- which helps buffer the usually acidic environment of the vagina to protect sperm.
During reproduction, where do the majority of sperm die?
After ejaculation when the semen coagulates in anterior vagina near cervical os (99% of sperm die here)
What does the sperm acrosome contain to help penetrate the zona pellucida?
Proteolytic enzymes
What is the main oestrogen in pregnancy, which is an indicator of foetal wellbeing (decline in this oestrogen correlates with foetal distress)?
E3 (Oestriol)
Around day 6-7 after fertilisation, trophoblast cells of blastocyst secrete hCG. Why is this important to maintain the pregnancy?
hCG prevents luteal regression of corpus luteum in the ovary, to ensure corpus luteum continues producing progestins until the placenta forms and takes over.
What is the decidua?
The modified endometrium that forms each menstrual cycle in preparation for pregnancy; it permits invasion of blastocyst for implantation.
(The part of the decidua that interacts with the trophoblast is the decidua basalis).
The cytotrophoblast (CTB) progenitor cell is the stem cell of the trophoblast that differentiates into two different phenotypes.
Which type invades the spiral artery of the endometrium to form the placenta?
EVT (extra-villus trophoblast)
The cytotrophoblast (CTB) progenitor cell is the stem cell of the trophoblast that differentiates into two different phenotypes, one of which is the syncitiotrophoblast.
What feature of the syncitiotrophoblast allows to to be effectively invisible from the maternal immune system?
Lacks certain antigens (self/non-self markers).
What are the key roles of syncitiotrophoblast cells in the placenta?
Syncitiotrophoblasts form the placental interface (between maternal and foetal blood), and are therefore involved in oxygen transport, nutrient and waste product handling, and production of hormones.
Why can the type of uterine natural killer cells (uNK) affect risk of miscarriage due to poor implantation/failure of implantation?
Certain types of uNK (KIR-B) bind well with trophoblast cells, uNK are then activated and produce growth factors to help the placenta develop. Other types do not and can lead to poor EVT (extra-villus trophoblast) invasion.
Spiral artery (SpA) remodelling is essential for a successful pregnancy.
During implantation, EVT (extra-villus trophoblast) cells invade the spiral artery. What structural changes do EVT cells have on the spiral arteries?
Increase lumen to increase blood flow to the foetus.
When post-fertilisation is interstitial implantation complete?
Day 6-12
What maternal immunoglobulin can cross the placenta?
IgG
What two structures compose the placenta?
Chorion (foetal) and endometrium (maternal).
Why does the placenta contain villous chorion?
The villi of the chorion increase the surface area for exchange of nutrients/waste between foetal and maternal blood supply.
What are the functional units of the placenta called?
Cotyledons
What paired exocrine glands in the male reproductive system located below the prostate, produce a clear, mucus-like fluid that lubricates the urethra and neutralises acidity in preparation for ejaculation?
Bulbourethral glands
What is the main function of the cremaster muscles?
Help control the temperature of the testis; aim is to keep them 3 degrees cooler than body temperature.
If it’s cold, they contract to raise the scrotum closer to the body.
If it’s warm, they relax so the scrotum is further away from the body.
How does the pampiniform plexus help keep the tesis 3 degrees cooler than body temperature?
Pampiniform plexus is a network of veins surrounding the testicular artery. The veins cool blood in the artery arriving to the testis.
What is the main function of the dartos muscle (tunica dartos)?
Contracts to wrinkle the skin, reducing surface area for heat loss. Opposite occurs in warm conditions.
What divides the scrotum and is formed by fusion of urogenital folds during embryological development?
The perineal raphe.
Why do sertoli cells in the testis have tight junctions between them?
To form a barrier (the blood-testis barrier) to prevent immune cells from entering seminiferous tubules and destroying sperm.
Spermatogenesis takes 64-72 days in humans.
What are the 4 steps of spermatogenesis?
- Spermatocytogenesis - mitotic division of spermatogonia (stem cells) to primary spermatocytes
- Spermatogenesis - meiotic division of spermatocytes into spermatids
- Spermiogenesis - maturation from spermatids to spermatozoa
- Spermiation - release into tubule lumen
What growth factor do sertoli cells secrete to inhibit the secretion of follicle-stimulating hormone (FSH) from the pituitary gland?
Inhibin
Why do women often get swollen ankles when pregnant?
Increased fluid retention; up to 50% increase in total plasma volume.
Reduced venous return due to uterus putting pressure on IVC.
(Severe swelling could be a sign of pre-eclampsia.)
What causes pregnant women to have a more active RAAS, causing fluid retention?
The ovaries and the decidua produce renin.
Oestrogens stimulate the liver to increase production of angiotensinogen.
What happens to plasma oncotic pressure during pregnancy?
Decreases - because there is dilution of serum albumin due to increased plasma volume/fluid retention.
During pregnancy, kidneys increase in size by up to 20% at term, due to dilation of the renal pelvis and calyxes.
What mechanisms cause this and also an increased risk of UTI in pregnant women?
Slower flow of urine because:
Reduced ureteral tone/peristalsis - due to relaxation of smooth muscle.
Gravid uterus compresses ureters.
What causes dilution anaemia in pregnancy?
During pregnancy, production of RBCs increases, but does not keep up with the increase in plasma volume, so RBCs are more diluted.
What happens to WBC count during pregnancy?
Increases.
During pregnancy, what three proteins increase, causing a hypercoagulable state and increasing the risk of thromboembolism?
Plasma fibrinogen, clotting factors, and PAI (plasminogen activator inhibitor).
During pregnancy, total lung volume decreases due to the gravid foetus raising the diaphragm.
What happens to tidal volume during pregnancy, partly due to progesterone-induced relaxation of tracheo-bronchial smooth muscle?
Increases
What happens to partial pressure of CO2 during pregnancy? What causes this?
Decreases.
Progesterone causes the respiratory centre chemoreceptors to be more sensitive to CO2.
Why is it important for the foetus that the maternal partial pressure of CO2 is low?
There needs to be a gradient between foetal CO2 and maternal CO2 for the CO2 to diffuse across the placenta.
Pregnancy is a state of compensatory respiratory alkalosis. Why?
Low CO2 (due to increased minute volume “blowing off CO2”) = alkalosis.
Renal compensation occurs by excreting more bicarbonate ions.
What two factors about maternal RBCs and foetal RBCs help ensure foetal RBCs have an increased affinity for oxygen compared to maternal RBCs?
Maternal RBCs have increased levels of 2,3 DPG. This binds to Hb and changes shape to reduce O2 affinity.
Foetal RBCs contain low levels of 2,3 DPG and foetal Hb, which has a different structure (2 alpha and 2 gamma instead of 2 beta chains) which has an increased O2 affinity.
Progesterone causes smooth muscle relaxation. What affects does this have on the gastrointestinal/hepatic systems during pregnancy?
Acid reflux due to relaxation of lower oesophageal sphincter.
Delayed gastric emptying and gut transit time; causes increased nutrient uptake but also reabsorption of water which can lead to constipation.
Reduced gall bladder motility; increased concentration of bile acid, increased risk of gall stones.
With reference to the placental glucose transporter, why is maternal hyperglycaemia dangerous for the foetus during pregnancy?
Placental glucose transporter does not limit uptake, so foetal glucose levels are directly related to maternal glucose levels. Hyperglycaemia can cause significant foetal harm e.g. deformities and macrosomia (large birth weight).
During pregnancy, the foetus releases hPL which is a insulin antagonist. What affect does this have in the mother?
Induces increased insulin resistance.
How much does the normal adult human testis weigh?
15-19g
