Case 14- gametes and placenta Flashcards
Where the Sperm travels from
Sperm is produced within the seminiferous tubules of the testes. Sperm will travel from the Rete testes, through the Efferent ductules and into the Epididymis where they will mature. It then enters the ductus vas deferens which travels through the spermatic cord and into the inguinal canal. The ampulla of the ductus then joins with the seminal vesicle, this forms the ejaculatory duct which joins with the prostate. The Bulbourethral glands also connects to the urethra which goes through the penis.
The two processes of Spermatogenesis
Spermatocytogenesis and Spermiogenesis
The 4 stages of Spermatocytogenesis
Spermatogonia -> Primary Spermatocyte -> Secondary Spermatocyte -> Spermatids.
Spermatogonium
Primary spermatogonium are diploid. They undergo mitosis to maintain the stem cell population before meiosis starts. The role of Primary Spermatogonium type A is to replenish the population through mitosis, to maintain male fertility. Primary Spermatogonium type B eventually go on to form the mature sperm.
Process of Spermatocytogenesis
1) Primary Spermatogonium type B
2) Primary Spernmatocyte which are diploid. This undergoes Meiosis 1
3) Two Secondary Spermatocytes which are haploid. They undergo Meiosis 2
4) Four spermatids which are also haploid.
Sertoli cells structure
1) The Sertoli cells are bound together by tight junctions, forms an unbroken layer in the Seminiferous tubule.
2) Helps form the blood testes barrier.
3) The tight junctions divide the Sertoli cells into a Basal compartment and an Adluminal
compartment.
4) The Basal compartment contains the Spermatogonia, the Adluminal compartment contains the Primary Spermatocytes, the Secondary Spermatocytes and the Spermatids.
Role of Sertoli cells
- Guides sperm towards the lumen, forms and re-forms junctions, making contact with the sperm cells. Sperm cells are produced within the seminiferous tubules of the sertoli cells
- Blood testes barrier- formed from tight junctions, immunologically safe microenvironment.
- Secretes fluid- moves immobile sperm to epididymis
- Transfer of nutrients- to keep sperm alive
- Phagocytosis- gets rid of residual cytoplasm and dead sperm.
- Expresses FSH receptors and androgen receptors
- Produces ABP, inhibin, AMH and oestrogen
Spermiogenesis
The second process of sperm production, where spermatids are converted into Spermatozoa, through development and maturation
Process of Spermiogenesis
- The pieces of the Golgi body come together to form the Acrosome, which sits at the head of the nucleus
- The mitochondria arrange themselves in a parallel position around the tail
- A tail starts to form
- The mitochondria move to the start of the tail. The centriole is the midpiece of the sperm.
- The Sertoli cells remove the residual cytoplasm
- The resultant spermatozoa are not mature and are immobile.
- The Sertoli cells will flush the Spermatozoa to the Epididymis cells where they mature and become mobile.
Structure of sperm
The head of the sperm contains the DNA and the acrosome which contains the enzymes for penetrating the oocyte. The neck contains the centriole which is needed for the formation of the tail. The midpoint contains mitochondria which is the energy store for cell movement. The tail propels the sperm forward.
How often does sperm production take
64 days, occurs in waves. You need to wait 64 days before giving sperm sample
Semen composition
5-10% of semen is sperm, the rest is seminal plasma i.e. extracellular fluid
Is fluid secreted from the Epididymis
yes
Seminal vesicle
Contributes 60-70% of the final volume of the semen. The secretion from the seminal vesicle is a thick alkaline fluid which protects sperm from the acidic nature of the urethra and female reproductive tract, Secretes its fluid at the start of the ejaculatory duct
Components of the seminal vesicle secretions
- Fructose- energy source for the sperm
- Prostaglandins- lowers the female immune response to semen, improves sperm motility to the uterine tubes.
- Coagulation factors- coagulates semen to help deliver sperm as directly as possible to the cervix.
Ejaculatory duct
The duct of the seminal vesicle joins with the ampulla of the ductus deferens to form the ejaculatory duct. Within the prostate the ejaculatory duct joins the urethra
Prostatic secretions
Contributes 20% of the total volume of semen, secretes into the Prostatic urethra. It is a thin milky fluid which contains citric acid, zinc and proteolytic enzymes. It contains a Prostate specific antigen which liquifies the coagulated ejaculate once the sperm is at the cervix. The antigen only acts 20 minutes later and helps the sperm move through the uterine tubes.
Bulbourethral glands
Pea sized glands embedded within the external urethral sphincter. It sits between the pelvic floor and the urogenital triangle. It drains into the Spongy urethra. Within the deep perineal pouch. It secretes mucus/ lubricating secretions which is the final volume of sperm. Helps with the passage of sperm through the urethra.
Types of fluid that contribute to semen
Testes- sperm
Epididymis- epididymal fluid
Seminal vesicles- thick alkaline fluid with fructuse, prostaglandins and coagulation factors
Prostate- thin milky fluid containing citric acid, zinc and proteolytic enzymes
Bulbourethral glands- mucus/lubricating secretions
Typical sperm count
- Semen volume: 1.5ml or more
- pH: 7.2 or more
- Sperm concentration: 15 million spermatozoa per ml or more
- Total sperm number: 39 million spermatozoa per ejaculate or more
- Total motility (percentage of progressive motility and non‑progressive motility): 40% or more motile or 32% or more with progressive motility
- Sperm morphology (percentage of normal forms): 4% or more
- Vitality: 58% or more live spermatozoa
What develops as the embryonic pole
Chorionic frondosum, the amniotic membrane, chorion leave and decidua parietalis
How maternal blood enters the placenta
Blood enters through the spinal arteries in the wall of the uterus and moves into the intervillus space. The blood flow slows to allow adequate exchange. After bathing the villi the blood drains into larger maternal placental veins.
How foetal blood enters the placenta
Once the blood has obtained O2 and nutrients it flows back to the foetus through umbilical veins carrying oxygenated blood. Umbilical arteries which bring waste from the foetus carry deoxygenated blood which returns to the maternal system.
Adaptions of the Placenta
The maternal blood has high pO2 and low p CO2. The placenta has numerous villi that increase the surface area. The thickness of the synctiotrophoblast at the terminal villi is very thin aiding gaseous exchange.
The placenta is less efficient then the lungs in exchange- how does the conceptus receive sufficient oxygen?
- The difference of oxygen/carbon dioxide concentration in the feto-maternal system
- Fetal haemoglobin has a higher affinity for oxygen as 2-3 DPG is unable to bind to Fhb. The graph shifts to the left.
How are carbohydrates transferred across the placenta
Carbohydrate transfer is by facilitated diffusion via the carrier protein Glut. Glucose provides 90% of the energy requirements for the fetus, only sugar that can cross the placental membrane. Used in oxidative metabolism. Glucose uptake is not regulated by insulin, the fetus will take glucose if its available in the maternal blood stream. Excess fetal glucose is stored in the muscle, liver and placenta.
How do fats cross the placenta
Fats are broken down and transported to the maternal blood as free fatty acids bound to albumin or lipoproteins or proteins packed chylomicrons. Once broken down the lipids move either by simple diffusion or facilitated diffusion down the concentration gradient. They are:
• Basic constituent parts of the lipid membrane
• Act as fuel for oxidative metabolism
• Precursors for important compounds i.e. prostaglandins
How does the fetus store energy
Glycogen stores in the fetal liver are double that of an adult but this falls within hours of birth
How are amino acids transported across the placenta
Higher concentration of proteins in the fetus so secondary active transport is required. The movement of amino acids is coupled with the movement of sodium into the fetus. Role of amino acids:
• The formation of proteins and growth
• Energy store
• Fetal hepatocytes can modify maternal amino acids if there is a shortage of a particular type.
• Fetal hepatocytes can develop new amino acids via de novo synthesis.
How high molecular mass compounds move across the placenta
Unable to cross the villi. Microdroplets of the compound are engulfed in the cytoplasm of the synctiotrophoblast and transported within small vesicles to the fetal circulation. Process of pinocytosis. Used for immunoglobulins.
How vitamins are transported across the placenta
Fat soluble vitamins diffuses across lipid membranes either by simple or passive diffusion. Active transport is required for water soluble vitamins to cross the placenta membrane. Fat soluble vitamins (ADEK) are used in growth and differentiation. Water soluble vitamins (C,B) are Cofactors for enzymatic reactions.
How do waste products move across the placenta
They move down the concentration gradient into the maternal blood
How does Bilirubin move across the placenta
The fetal liver does not have glucuronic acid and is unable to process it, bilirubin is insoluble in the fetal system. The unconjugated bilirubin is transferred to the maternal system. The adult liver converts unconjugated bilirubin to conjugated bilirubin using glucuronic acid. Conjugated bilirubin moves to the gut tube where it is excreted or reabsorbed.
Placental insufficiency
When the placenta cannot provide oxygen and nutrients to support the growing fetus. It is the most common cause of fetal growth restriction. Regulation of blood flow is very important for placental function
Causes of Placental insufficiency
- Acute factors= maternal haemorrhage. Powerful, prolonged uterine contractions. Maternal inferior vena cava obstruction.
- Abnormal trophoblast invasion= Pre-eclampsia, Placenta accrete
- Tumours
- Placenta praevia
- Placental infarction
- Placental abruption
- Abnormal umbilical cord or cord insertion
Maternal factors that can affect the function of the placenta
Chronic maternal disease i.e. hypertension, anaemia, autoimmune disease, substance abuse, smoking and malnutrition
Maternal factors that can affect the function of the placenta
Chronic maternal disease i.e. hypertension, anaemia, autoimmune disease, substance abuse, smoking and malnutrition
How do you screen for placental insufficiency
- Symphysis fundal height- the size of the bump is measured from the pubic symphysis to the uterine fundus. Done at every appointment.
- Ultrasound assessment of foetal growth- fetal head circumference, abdominal circumference and femur length can be used to assess growth on the ultrasound.
- Uterine artery doppler- an ultrasound that assesses the blood flow through the uterine artery and indicates resistance within the placenta. High resistance indicates poor uteroplacental blood flow. The umbilical artery Doppler is used instead of the uterine artery from the 3rd trimester onwards. Best indicator of placental functions
What do you test for if you are concerned about fetal wellbeing
- Biophysical profile- assess fetal breathing movements, body movements, fetal tone, fetal heart rate and amniotic fluid volume to determine how healthy the fetus is.
- Cardiotocography (CTG)- measures fetal heart rate
When do babies become clinically jaundiced
When their bilirubin levels reach 80µmol/l. Over 50% of new-borns become visibly jaundiced. In physiological jaundice there is no underlying pathological cause and occurs as the baby adapts to life outside the womb.
Causes of Physiological jaundice
- The lifespan of red blood cells in new-born babies is 70 days (compared to 120).
- Enterohepatic circulation is increased in new-born babies, increased unconjugated bilirubin in the blood
- The hepatic enzyme system which conjugates bilirubin is immature, baby can no longer rely on mother. Less bilirubin is conjugated and excreted.
Time period of physiological jaundice
Appears around 24 hours and resolves by 2 weeks, most common in breastfed infants
How to treat physiological jaundice
With blue light phototherapy which convertes unconjugated bilirubin into a soluble form which is excreted in the urine
Reproduction cycle
The physiological changes that occur beginning at conception and extend through gestation and parturition.
Menstrual cycle
Cyclical changes in the ovaries whereby the ovum develops for fertilisation and the uterus prepares for implantation. From puberty to menopause.
Ovarian cycle
Cycle of follicle growth resulting in ovulation and corpus luteum formation
Vasectomy
A small amount of the vas deferens is removed or cut and sealed by cautery. A small incision is made in the middle or on either side of the scrotum. Performed under local anaethesia. Confirmation of success requires postoperative semen analysis to confirm azoospermia. Failure rate is 0.05%. Prevents sperm entering the urethra, sperm is still produced but it broken down in the testes and reabsorbed.
Advantages of a vasectomy
Safe and very effective 0.05%, permanent, takes 10-15 minutes
Disadvantages of a vasectomy
Not easily reversible (psychological- regret), not effective immediately, no STL protection. Surgical procedure with short/long term effects (infection, bruising, bleeding and pain). Need to use contraception for 2-4 months till sperm analyses
Tubal litigation
The Fallopian tubes are blocked preventing fertilisation of eggs. Use general anaesthetics when done laparoscopically, can be done after a caesarean section. Reduces pregnancy rates but increases risk of an ectopic pregnancy.
Other surgical methods of female sterilisation
Hysterectomies (removal of the uterus) and Bilateral salpingoophorectomy (removal of the ovaries and fallopian tubes). Causes sterilisation but are complicated so not offered first line.
Non hormonal methods of contraception
Barrier (condoms, diaphragm, caps), copper IUD, sterilisation, natural family planning, withdrawal, Lactational amenorrhoea method (LAM), abstinence
What innervates ejaculation
Emission
Sympathetic L1-L2
Expulsion
Somatic
Pudendal nerve S2-S4
Advantages and Disadvantages of Barrier contraception
Advantages- no side effects easy to obtain and use can be effective STI protection requires no medical supervision
Disadvantages- Requires forward planning, need careful use, loss of sensitivity, may interrupt sex, can break
Caps and Diaphragm
flexible and thin
dome-shaped ring
different shapes and sizes so can fit most women
can remain in situ for up to 6 hours after sex
Advantages of caps and diaphragms
effective,
can be put in at any time before sex
can protect against PID and cervical cancers
non-hormonal
Disdvantages of caps and diaphragms
requires careful and constant use to be effective
not that effective
increase in cystitis and UTI’s in diaphragm users
must be used with spermacides
not suitable if a Hx of toxic shock syndrome
Progesterone only pill
no pill break, 12-hour window each day
inhibits ovulation, and thickens cervical mucus
POP advantages and disadvantages
Advantages very effective (99%) very safe doesn't increase breast cancer risk good for when oestrogen is contraindicated
Disadvantages menstrual disturbance side effects - breast tenderness - worsening acne - headaches - mood changes - affect bone mineral densities
COCP (combined oral contraceptive pill)
Negative feedback on pit. means LH and FSH release is inhibited, so ovulation is inhibited, also alters cervical mucus so inhibits sperm transport and surpasses endometrial growth
COCP advantages and disadvantages
Advantages reliable, reversible, relieves dysmenorrhoea, improved cycle control, improved acne, reduced risk of benign breast disease
Disadvantages needs correct usage unsuitable with certain contraindications and risk factors side effects often experienced no STI protection
The two main emergency contraception pill
Levonorgestral
Ulipristal
Emergency contraception MoA
Delays LH surge and so delays ovulation, but only if taken early enough in the cycle
97 - 99.5% effective depending on the method and timing
Natural family planning
Where women analyse their fertility signs to work out when they are likely to conceive. This can be effective but is difficult to measure and keep accurate notes. Fertility signs: temperature, fluids coming from your cervix. It takes 3-6 menstrual cycles to learn the method. Your fertility signs can be affects by illness, stress and travel. You avoid sex for 48 hours after ovulation and 7 days prior. Body temp rises by 0.2 degrees after ovulation (check in morning), so when temps are higher for 3 days the patient is no longer fertile.
Spermicide
- Nonoxynol-9 is used in the UK as a cream or pessaries
- Not suitable if at risk of HIV
- Cream inserted in the vagina before intercourse, not effective on its own
- MOA- spermicide kills sperm, alters integrity of sperm cell membrane, vaginal pH altered
- Advantages- no side effects, provides lubrication, enhances barrier methods
- Disadvantages- should not be used as sole contraception, irritation or allergy. Vaginal and urinary infections
Missing the pill POP
POP is taken within a 3 hour window, Desogestrial within a 12 hour window. If a pill is missed (3 or 12 hour window) take the next pill as soon as possible, even if you need to take two on the same day, then continue as normal. If they miss the pill 2 days in a row, they should the next pill as soon as possible and not have sex for 48 hours.
2 main actions of POP
- Thickens the cervical mucus making it more challenging for sperm to fertilise the egg
- Thins the lining of the uterus making it less likely a fertilised egg will implant
How long does it take for combined hormonal contraception to become effective
If you start the pill in the first 5 days of your menstrual cycle there will be immediate protection. If started on another day contraception is needed for 2 days.
If you miss one pill take the next pill, even if it means taking 2 in one day no other contraception is needed. If 2 or more pills are missed, take the last pill so 2 in 1 day, ignore any other missed pills. Use other contraception for 7 days.
MoA of COCP
Oestrogen feeds back to the Hypothalamus to supress LH and FSH, inhibiting ovulation
• Cervical mucus altered inhibiting sperm penetration
• Growth of endometrium suppressed
• Reduces chance of blastocyst implantation, inhibits sperm transport and the secretions in the fallopian tubes.
• Prevents ovulation, suppresses gonadotrophins by the hypothalamus and pituitary gland.
Who is the COCP not suitable for
- Migraine with aura, migraines that last 72 hours despite treatment, epilepsy
- Smoking, obesity- BMI>35kg/m^2
- Breast cancer
- Current or recent genetic mutation
- <21 days postpartum or <6 weeks if breast feeding. Pregnant
- After surgery/prolonged immobility
- Hypertension- over systolic 160 mmHg or diastolic 100 mmHg
- > 35 yo smokers
- Current/past VTE , IHD, stroke
- VTE in 1st deg relative <45 yo
- Diabetes with complications
- Liver diseases, medication which uses liver enzyme inducing drugs (i.e. for epilepsy, anti-retroviral and St Johns Wort)
Avoid the COCP if 2 or more of the following risk factors are present
- Obesity (BMI >30kg/m2)
- Smoking
- Diabetes melitus
- Family of arterial disease in first degree relative under 45
- Blood pressure above systolic 140 mmHg or diastolic 90 mmHg
- Migraines without aura
The two types of Intrauterine copper devices
- Copper coil- small amounts of copper are released, this increases cervical mucous, prevents implantation of an egg. Lasts 5-10 years
- LNG-IUS= similar to POP. Thickens cervical mucosa, thins the uterine lining so the egg is less likely to implant. May prevent ovulation in some women, but most continue to ovulate. Lasts 3-5 years for LNG-IUS
Disadvantages to the coil
Small infection risk, more invasive, small risk the coil can be disloged, uterine damage, no STI protection, uncomfortable after insertion.
Contraceptive implant
Most effective type of contraception. It steadily increases progesterone into the blood which prevents ovulation, thickens mucus and thins the uterine lining. Works in same way as POP. If fitted in the first 5 days there is immediate protection otherwise contraception is required for 7 days. It lasts 3 years and can reduce symptoms of heavy or painful periods
Contraceptive injection
Most common is ‘Depo-provera’, given every 13 weeks for most types. Simple to administer, less permanent, can occur at any point in the menstrual cycle. If injected in the first 5 days of the menstrual cycle there is immediate protection, otherwise contraception is needed for 7 days.
