Reproduction Flashcards
When does oogenesis begin and begin again after suspension?
Begins in utero, begins again at puberty
When does oogenesis complete?
Fertilisation
When does oogenesis cease?
Menopause
What is the primordial germ cell?
Earliest recognisable germ cell
When do the primordial germ cells migrate to the genital ridge by?
Week 6 of embryo development
What are oogonia?
Small diploid cells which on maturation form primordial follicles
What does the presence of two polar bodies signify?
Sperm entry and completion of 2nd meiotic division
What are the two phases of the ovarian cycle?
Follicular phase and luteal phase
What happens in the follicular phase?
Maturation of egg, ready for ovulation at midcycle- ovulation signals end of follicular phase
What happens in luteal phase?
Development of corpus luteum. Induces preparation of reproductive tract for pregnancy
What is the primary follicle?
A structure made up of the primary oocyte surrounded by a single layer of granulosa cells
How many ovum is a primary follicle capable of producing?
1
How does the secondary follicle occur?
Oocyte grows and follicle expands and becomes differentiated under hormonal influence. After puberty about 400 will be ovulated, rest undergo atresia. Follicular phase ends with ovulation
What happens to follicular cells left behind after ovulation?
They undergo luteinisation- transformation into the corpus luteum
What does the corpus luteum secrete?
Progesterone
If no fertilisation occurs, how long will the corpus luteum survive?
No longer than 14 days after ovulation
What signals the start of a new follicular phase?
Degeneration of corpus luteum
What happens to the corpus luteum if fertilisation occurs?
It persists and produces increasing quantities of progesterone and oestrogen until after pregnancy
What is secreted from the hypothalamus that acts on the anterior pituitary?
GnRH
What does the anterior pituitary secrete with regards to ovarian action?
FSH and LH
What does FSH to do the ovary?
Stimulates follicular development, along with LH stimulates secretion of oestradiol and ovulation
What does LH do to the ovary?
Stimulates follicle maturation, ovulation and development of corpus luteum
What hormonal secretions happen in the follicular phase?
Hypothalamus secretes GnRH, in response Ant Pituitary secretes FSH and some LH. Rescues about 15 follicules- their granulosa and theca cells develop
What do the theca cells of the ‘rescued’ follicles do?
Produce androgen which is converted by the granulosa to oestradiol
What does oestradiol do to the uterus?
Thickens endometrium/thins cervical mucus
What does oestrogen do to FSH?
Suppresses its production by ant. pituitary (dominant follicle selection)
What does granulosa in the dominant follicle express?
LH receptor
What does high levels of oestrogen mid cycle cause?
Hypothalamus to release GnRH, causes FSH/LH surge from AP
What happens to the corpus luteum at 12 days if there is no hCG production from an embryo?
Corpus luteum degenerates forming the corpus albicans, leading to progesterone and oestrogen levels falling
What does the developing embryo produce which maintains the corpus luteum?
hCG-Human Chorionic Gonadotrophin
What does the placenta take over at around 6 weeks?
Progesterone production from corpus luteum, it therefore degenerates forming the corpus albicans
Where does glandular oestrogen synthesis occur?
In the granulosa and theca cells of the ovaries, aswell as the CL
What is the pathway of pregnenolone to oestradiol?
Pregnenolone diffuses out of granulosa to adjacent theca cells. These cells express 17,20-lyase and 3B-HSD, which mediate pregnenolone to androstenedione conversion via DHEA. Most androstenedione returns to granulosa and is converted to oestrone by aromatase, then is converted to oestradiol by 17B-HSD
What is the expression of aromatase and 17B-HSD controlled by?
FSH stimulation
What does aromatase do outwith gonadal sites?
Facilitates peripheral aromatisation of androgens to estrone
What is progesterone synthesised by?
From pregnenolone by the action of 3B-HSD in the corpus luteum, by the placenta during pregnancy and by the adrenals, as a step in androgen and mineralocorticoid synthesis
What is oligomenorrhea?
Reduction in frequency of periods to less than 9/year
What is primary amenorrhea?
Failure of menarche by the age of 16 years
What is secondary amenorrhea?
Cessation of periods for >6 months in an individual who has previously menstruated
What are the causes of primary amenorrhea?
Congenital problems (Turner’s, Kallman’s)
What are the causes of secondary amenorrhea?
Ovarian: PCOS, POF. Uterine: uterine adehsions. Hypothalamic dysfunction: wt loss, over exercise, stress, infiltrative. Pituitary: high PRL, hypopituitarism
What should be asked about in the history of secondary amenorrhea?
Oestrogen deficiency symptoms: flushing, libido, dyspareunia. Hypothalamic: exercise, wt loss, stress. Features of PCOS/androgen excess: hirsutism/acne. Anosmia: Kallmans. Hypopituitarism/pituitary tumour symptoms: galactorrhea. Drugs associated with hyperprolactinaemia
What should be looked for in an examination of a patient with 2’ amenorrhea?
Body habitus: Turners. Visual fields/anosmia. Breast development. Hirsutism/acne/androgen excess
How should amenorrhea be investigated?
LH/FSH/Oestradiol. TFT, PRL. Additional: ovarian US +-endometrial thickness. Testosterone if hirsutism. PFTs +MRI pituitary. Karyotype
How is female hypogonadism identified?
Low levels of oestrogen
What is seen in primary hypogonadism?
Problem with ovaries. High LH/FSH-hypergonadotrophic hypogonadism. e.g. POF
What is seen in secondary hypogonadism?
Problem with hypothalamus/pituitary. Low LH/FSH: hypogonadotrophic hypogonadism. e.g. high PRL, hypopituitarism
How does POF present?
Amenorrhea, oestrogen deficiency and elevated gonadotrophins occuring
How is POF diagnosed?
FSH >30 on 2 separate occasions > 1 month apart
What are the causes of POF?
Chromosomal abnormalities (e.g. Turner’s syndrome, Fragile X) Gene mutations (e.g. FSH receptor/LH receptor) Autoimmune disease (e.g. association with Addison’s, thyroid, APS1/2) Iatrogenic (radiotherapy/chemotherapy)
What are the causes of 2’ hypogonadism?
Hypothalamic problem: Functional hypothalamic disorders, Kallman’s syndrome, Idiopathic hypogonadotrophic hypogonadism (IHH). Pituitary problems. Miscellaneous: Prader-Willi, Haemachromatosis
What can cause functional hypothalamic amenorrhea?
Weight change Stress Exercise Anabolic steroids Systemic illness Iatrogenic (surgery/radiotherapy) Recreational drugs Head Trauma Infiltrative disorders e.g sarcoidosis
How is idiopathic hypogonadotrophic hypogonadism identified?
By absent or delayed sexual development associated with inappropriate low levels of gonadotrophin and sex hormone levels in absence of anatomical / functional defects of hypothalamic-pituitary gonadal axis
What is Kallman’s syndrome?
A genetic disorder characterised by a loss of GnRH secretion and anosmia or hyposmia
What are the ovarian causes of amenorrhea?
PCOS, ovarian failure, congenital problem with ovarian development
What are the causes of hirsutism?
PCOS, familial, idiopathic, non-classical congenital adrenal hyperplasia, adrenal or ovarian tumour
What is congenital adrenal hyperplasia?
CAH is an inherited group of disorders characterised by a deficiency in one of the enzymes necessary for cortisol synthesis-90% dye to 21a-hydroxylase deficiency. Autosomal recessive. Varied clinical presentation
What is the genetic abnormality in Turner’s?
Females only have 1 x chromosome
What are the key clinical features of Turner’s?
Short stature, webbed neck, shield chest with wide spaced nipples, cubitus valgus. Failure to progress though puberty
What are the CVS complications of Turner’s?
Coarctation of aorta, bicuspid aortic valve, hypoplastic left heart
What are the GI complications of Turner’s?
Bleed (vascular malformation), increased IBD
What are some non CVS/GI complications of Turner’s?
Lymphoedema, AI hypothyroidism, osteoporosis, scoliosis, otitis media, renal abnormalities
How does male 1’ hypogonadism present?
Low testosterone with high LH/FSH, Acquired and congenital causes
How does male 2’ hypogonadism present?
Low testosterone with inappropriate low LH/FSH. Pit/hypothalamic disease
What is the karyotype in Klinefelter’s?
47 XXY
What are the clinical featres of Klinefelter’s?
Reduced testicular volume Gynaecomastia Eunuchoidism (intellectual dysfunction in 40%) (azoospermia)
What are the congenital/idiopathic causes of 2’ hypogonadism?
Idiopathic hypogonadotrophic hypogonadism (IHH) including Kallman’s syndrome (i.e. with anosmia)
Congenital adrenal hyperplasia
What are the functional causes of 2’ hypogonadism?
Exercise, weight change, stress, systemic illness
Infiltrative disorders – sarcoid, haemachromatosis,
Cranial irradiation / trauma
Drugs (e.g. anabolic steroids, opiates)
Hyperprolactinaemia
Hypothalamic or Pituitary tumours / surgery
Prader-Willi syndrome
What are the benefits of testosterone replacement?
Improved sexual function, bone health, body composition/muscle strength, QOL and cognition, insulin sensitivity and diabetes. Will not aid fertility (may act as contraceptive)
What are the causes of gynaecomastia?
Physiological
Drugs: Oestrogens, testosterone, spironolactone, digoxin +many more
Hypogonadism
Tumours; Oestrogen/androgen testicular or adrenal origin, hCG secreting (e.g. germinoma)
Endocrine disorders (e.g. thyrotoxicosis, Cushings)
Systemic illness
Hereditary disorders
What investigations are carried out in gynaecomastia?
Testosterone, LH/FSH. Oestradiol, PRL, AFP, HCG, LFTs, SHBG. Breast imaging, testicular/adrenal imaging
What is the treatment of gynaecomastia?
Address underlying cause. Reassurance. Surgery, medication (e.g. anti-oestrogens)
