Reproduction Flashcards
Up to what week of foetal development are humans indifferent?
Indifferent until week 7
What is the default gender pathway?
Female
What the factors involved in producing a male foetus?
SRY - transcription factor expressed by the Y chromosome
Androgens and AMH are important signals in males
Where do the primordial germ cells migrate to ?
migrate to the genital ridge
What is the flow of cells produced during oogenesis?
Primordial germ cell Oogonia Primary oocyte Secondary oocyte Mature oocyte
What is significant about meiosis and what is the purpose of producing polar bodies during oogenesis?
Discontinuous - primary oocytes are all ready and waiting before a foetus is born and the cells are arrested in
prophase I, and then by puberty the secondary oocytes are arrested in metaphase II until a sperm fertilises them
-finite number of egg cells - born with all the eggs we will ever have
- up to week 20 there is massive proliferation of oogonia but in the second half of pregnancy there is significant atresia
Help the egg to get rid of excess genetic material
What are the different stages of follicles?
Primordial follicle (formed in utero), primary follicle (pre-antral), secondary follicle (pre-antral), tertiary follicle (antral/graafian follicle)
When and why does the blood-testis barrier form?
Develops during puberty to protect the sperm from the immune system and controls what enters and exits the seminiferous tubules
Forms between the sertoli cells
What is the flow of cells produced during spermatogenesis?
Primordial germ cells Prospermatogonia - at genital ridges Spermatogonial stem cells Primary spermatocytes Secondary spermatocytes Round spermatids Elongated spermatids Spermatozoa
What is the purpose of the centrioles in the sperm?
eggs don’t have centrioles so these centrioles are essential for the first cell division
Why does the sperm shed its cytoplasm?
Sheds it to make them more streamline
What does LH stimulate in the male HPG axis?
leydig cells to produce androgens (testosterone)
What does LH stimulate in the female HPG axis?
Theca cells - androgens which are aromatised in the granulosa cells by aromatase to produce oestrogens
What does the corpus luteum produce?
Oestrogen and progesterone
What are the 3 main families of steroids?
Estrogens
Progestins
Androgens
What do high levels and low levels of oestrogen do to the HPG axis?
High levels stimulate the anterior pituitary to release FSH/LH
Low levels inhibit the hypothalamus and anterior pituitary from releasing GnRH and LH/FSH respectively
Define:
Normal menstrual cycle
Oligomenorrhoea
Amenhorrhoea
Normal menstrual cycle = bleed every 28 days (26-32days)
Oligomenorrhoea =<9 cycles in the last 12 months
Amenhorrhoea = no bleed in the last 6 months - before puberty = primary whereas periods stopping = secondary
Which phase varies and subsequently affects the length of a female menstrual cycle?
variations in the follicular phase length (pre-ovulatory phase)
What are some causes of amenorrhoea?
ALWAYS exclude pregnancy
Central causes: hypothalamic (low leptin, Kallman syndrome), pituitary (hyperprolactinaemia, tumour ) (Low FSH/LH) = suppresses the HPG axis
Ovarian causes: Turners (X -), premature ovarian failure (elevated FSH/LH- brain is functioning but ovaries are not)
What is polycystic ovary syndrome?
Commonest endocrine condition (>10% of pre-menopausal women)
Symptoms: hyperandrogenic, insulin resistance, PCO
Rotterdam criteria- diagnosis criteria requiring you to have 2 out of 3 symptoms:
1) poly cystic ovaries
2) hyperandrogenism
3) oligomenoorhoea (80%)
Other common symptoms - hirsuitism (30%)- excess body hair due to high levels of androgens - obesity (40%) - infertility (30%) Unknown aetiology
What are examples of male endocrine disorders?
Delayed puberty Reduced libido Gynaecomastia Reduced shaving frequency Reduced testicular volume Infertility
What are the primary causes of gonadal failure?
High FSH, LH
Trauma, chemo, surgery, cryptochidism (testes fail to descend), infections/inflammation, genetic (Klinefelter’s - sometimes not picked up until infertility clinic)
What are the secondary causes of gonadal failure?
Low FSH, LH
Hypothalamic disorders (Kallman), hyperprolactinaemia
Pituitary tumours, androgen abuse
What are some other endocrine disorders affecting reproduction?
Congenital adrenal hyperplasia (21-OHD)- decreased cortisol and aldosterone and increased testosterone
Androgen insensitivity syndrome - androgen receptor
What are the prerequisites for fertilisation?
Sperm and oocyte in ampulla in the correct state
- oocytes - 24 hours its completed meiosis I and has started meiosis II but is arrested in metaphase II
- Capacitation of the sperm = final maturation process which takes place in the female tract - only once this has occurred can it fertilise the ovum
How long can sperm remain in the female tract?
Sperm can remain there for about 5 days but the egg of only viable for about 24 hours so there is a relatively small window for fertilisation to take place
What happens when the sperm fuses with the egg?
Sperm fusions triggers calcium increase = releases meiotic block, block to polyspermy (egg has evolved special mechanisms to prevent more than one sperm fusing with the egg)
Fast reaction = membrane depolarisation
Slow reaction = cortical reaction
Only about 10-100 sperm actually reach the ampulla
What defines the end of fertilisation?
Male and female pronuclei migrate towards each other and combine forming a zygote nucleus
- then cleavage commences
- implantation occurs at around day 7
How many couples have infertility problems ?
1 in 6 couples
15% unexplained - could be due to minor problems in both partners
What female factors can be involved in infertility?
Ovulatory disorders, tubal damage (blocked fallopian tube), endometriosis, uterine abnormalities, implantation/growth/development
What male factors can be involved in infertility?
Sperm production, sperm transmission, sperm transport (many are not capable of traversing the female tract), fertilisation and development
What diagnostic procedures are available to determine infertility?
Blood tests - endocrinology - FSH/LH/Progesterone
Hysterosalpinogram, laparoscopy
Semen analysis: normozoospermic, oligozoospermic (too few sperm), asthenozoospermic (low motility), tetratozoospermic (abnormal morphology), azoospermic (no sperm)
What treatment approaches are their available for infertility?
Ovulation induction - estrogen inhibitor to induce ovulation
IUI - interuterine insemination - directly inserting sperm into the uterus - the timing is key
IVF
ICSI - intracytoplasmic sperm injection
Ovarian stimulation = IVF and ICSI - stimulate a women to produce about 10-15 eggs a month
Donor gametes/embryo
What are the types of contraception?
Hormonal - COC, POP, patch, implant, injection, ring
Barrier - Condoms, diaphragm, cap, spermicides
IUD/IUS (cu coil, mirena)
Sterilisation
Natural methods
Emergency contraception
Termination of pregnancy
LARCs = long acting reversible contraceptives e.g. implant, coil, injection
What is the first hormone produced during pregnancy?
hCG - developing embryo (it enables survival of the corpus luteum)
What are the key factors involved in parturition?
Increased oestrogen:progesterone stimulates contraction
Fetal corticosteroid release stimulates oestrogen and prostaglandin synthesis (cervical softening and dilation, muscle contraction)
Ferguson reflex (release of oxytocin in response to pressure on cervix, +ve feedback, prostaglandin release)
Relaxin - pelvic ligaments and softens cervix
What hormones are involved in stimulating the development of breast tissue?
Oestrogen, progesterone, hPL and prolactin
What inhibits milk secretion during pregnancy?
Steroid hormones and hPL inhibit milk secretion
What is the letdown reflex?
Prolactin causes milk synthesis, stimulation of the nipple causes oxytocin release to trigger milk ejection and continued prolactin production
Prolactin release inhibits FSH and LH - lactational amenorrhoea
What physiological changes occur in the mother during pregnancy?
Cardiovascular adaptations - cardiac functioning and haemodynamic changes
Placenta - development and structure, transport, immune privilege
Regulation of uterine activity: myometrium - suppressed during pregnancy but switched at birth
What are some examples of different screening tests during pregnancy?
urine dipstick, USS, combined test/triple/quad test, nuchal translucency, ffDNA
What other tests can be looked into during pregnancy?
Genetic tests (pedigrees), ancestry
What are some common complications during pregnancy?
Pre-eclampsia: characterised by onset of high blood pressure and high concentration of protein in urine
Gestational diabetes mellitus
What are the definitive signs of puberty?
Females: menarche Males: first ejaculation other factors: - growth spurts - Secondary sex characteristics - timings vary between individuals and be used for staging (Tanner)
How are the female secondary sex characteristics developed?
Ovarian oestrogen leads to the development of breasts and genitalia
Ovarian and adrenal androgens leads to the development of pubic and axillary hair
How are the male secondary sex characteristics developed?
Testicular androgens leads to public and axillary hair growth, genitalia, enlargement of larynx and laryngeal muscles
Define: precocious puberty
onset of secondary sex characteristics before 8 years in girls and before 9 years in boys
- menarche before 9 years in girls is linked to short stature because the bone growth plate fuse early
Define: delayed puberty
absence of secondary sex characteristics by 14 years in girls and 16 years in boys
- delayed puberty may lead to osteoporosis
What is the suggested mechanism underlying puberty?
Hypothalamic maturation hypothesis - increased hypothalamic GnRH
Kisspeptin - GPR54
Leptin - body mass seems to be a key determinant for triggering puberty
What does the human fertilisation and embryology authority (HFEA) do?
Patient safety Welfare of children Policy making Embryo research Control over gametes and embryos
