Reproduction and development

Question 1

Describe the histological anatomy of the testes, ducts, accessory glands and penis.

Answer 1

Testes
- Contain lobules which consist of seminiferous tubules supported by interstitial tissues
- The tubules are lined with Sertoli cells which aid the maturation of spermatozoa. The interstitial tissue contain Leydig cells which allow for testosterone production
- Inside the scrotum the testes are covered in tunica vaginalis, a closed sac of peritoneal origin. Sac contains viscous fluid.
- Tunica albuginea, a fibrous capsule that encloses the testes. Divides in each testicles and creates different lobules.
The Epididymis
- Head: the most proximal part of the epididymis.
- Body: formed by coiled duct of the epididymis
Tail: The most distal part of the epididymis. It marks the origin of the vas deferens- transports sperm to the prostatic portion of the urethra for ejaculation.
Prostate
- Positioned inferiorly to the neck of the bladder and superiorly to the gland. Lies in the ampulla of the rectum
- Release proteolytic enzymes via the prostatic ducts which open into the prostatic portion of the urethra and each side of the colliculus.
- It is a roughly walnut shape
In diseases such as benign prostatic hyperplasia the prostate increases in size which may compress the urethra and cause difficulties in urination
- Different zones: fibromuscular stroma, transitional zone, central zone, peripheral zone. Cuboidal glandular epithelium.
Ductus Deferens
- tube that transfers sperm to the urethra for expelsion.
Seminal Vessicles- (superior to the prostate)
Penis
- It can be divided into 3 structural parts: The root which is located in the superficial perineal pouch and is not visible externally. Contains the erectile tissues in the form of the left and right crura and the bulb. The Body which is the ‘free’ part of the penis and suspended from the pubic synthesis. The Glans which is the most distal part of the penis- external urethral orifice. Corpus spongeiosum forms the glans.
- 4x muscles: 2x bulbospongeousis, 2x ischiocavernosis in bulb
- The body contains 3 cylinders of erectile tissue: 2 corpora cavernosa and one corpus spongiosum.

Question 2

Explain the blood to testes barrier.

Answer 2

Seperates blood vessels and lymphatic vessels from the seminiferous tissues of the testes. Develops at puberty, tight tissue barriers, similar to BBB. Sertoli cells provide support, tight junctions between cells. Protects the testes against toxic substances as well as maintaining environment.

Question 3

Explain the funcion of the male reproductive organs including spermatogenesis.

Answer 3

Urination and sexual intercourse. Production of hormones which are essential for labido and spermatogenesis..

Question 4

Describe the gross and histological anatomy of the ovaries, uterus, cervix and vagina.

Answer 4

Ovaries contain all of the oocytes that a woman will ever need. Histology of the reproductive organs are different dependent on the stage of the menstrual cycle.
Uterus is suspended by a broad ligament.

Question 5

Explain the importance of ligaments in the female reproductive system.

Answer 5

Is important for holding the uterus in place.
Broad ligament - extends from the sides of uterus to the lateral walls and floor of pelvis; made of mesosalpinx (encloses uterine tube), mesoovarium (carries ovarian vessels and nerves), mesometrium (contains part of transverse cervical ligament)
Uterovesical fold - extends from the junction of uterine body and cervix to the bladder; creates uterovesical pouch
Rectovaginal fold - extends from the posterior vaginal fornix to the rectum; creates rectouterine poch (of Douglas).
Weakening of the ligaments can leed to uteral prolapse.

Question 6

Explain the function of the female reproductive organs.

Answer 6

Creating an appropriate environment for feotal growth and birth.

Question 7

Describe the synthesis of the principle sex steroids and their effects on the body.

Answer 7

Oestrogen, Progesterone and Testosterone
- Synthesised from cholesterol, structurally differ due to the pattern of chemical bonds.
- lipid soluble, act on intracellular receptors, act on gene expression.
- They are produced mainly in the gonads
- Regulated by the pulsatile release of GnRH from the hypothalamus: acts on the production of LH and FSH in the pituitary> acts on Gonads> produce inhibin and sex steroids (negative feedback to hypothalamus and pituitary)> act on accessory sex organs and other tissues.
Testosterone and DHT are the most abundant androgens in males: Testoderone produced in Leydig cells and converted to DHT in target tissues by 5a reductase (highly potent).

Question 8

Describe the hormonal changes involved in the menstrual cycle

Answer 8

Menstrual cycle has 3 stages (2 phases) and lasts over 28 days
Follicular phase: 1-14
- Mensus: Proliferation of uterine endometrium. FSH stimulates ovary to produce follicle, secretes oestrogen
- Proliferative: Development secretory changes, graffian follicle develops under influence of FSH and low oestrogen.
Luteal phase: 14-28
- Secretory: desquanation of endometrium, Low oestrogen eventually inhibits FSH production and leeds to a rise in oestrogen production, stimulates LH surge and formation of corpus luteum: oestrogen and progesterone- inhibits LH and FSH. Degeneration of corpus luteum and drop of oestrogen and progesterone leads to menstruation. LH and FSH begin to rise again.

Question 9

Describe different hormonal contraceptives and their pros and cons.

Answer 9

Combined pill- synthetic oestrogen and progesterone, supresses LH and FSH (no follicles develop via negative feedback inhibition, leads to hostile thick mucous in some cases, reduced endometrial growth.
P- highly effective
C- CVS: can cause thrombosis, reports of strokes in young women, breast tumours

Progesterone only- thickened cervical mucous, sometimes stops ovulation, must be taken at the same time every day
C- spotting, mood swings

Injection- Progestin- every 13 weeks/ implantable rod for 3 years.

Question 10

Describe the stages of the sexual reflex and the neural control of each stage.

Answer 10

Initiated by a sexual stimuli
- Special senses or sexual fantasy.
- Non- genital erogenous zones
- External genitalea (pudendal nerve (ventral rami of S2-S4), female equivelent to penis is clitoris and crotum is labia majora)
(afferent part)
The reflex can be divided into 4 stages (efferent part):
Erection: Both males and females have erectile tissue: 2 Corpora cavernosa and Bulb of penis/vestibule. Branches of the pudendal artery, cavernous artery. Blood drains into cavernous sinus which drains into deep dorsal vein. Controlled by parasympathetic nerves originating from S2-S4. Parasympathetic nerves normally
utilise acetylcholine but in erectile tissue use nitric oxide (NO) instead. contraction of perineal muscles: Ischiocavernosus, Bulbospongiosus (Supplied by somatic
nervous system – pudendal nerve (S2-S4))
Emission: Emission in males is the release
of secretions by the vas deferens, prostate, seminal vesicles and bulbourethral
(Cowper’s) glands into the penile
urethra. Emission in females is the
release of secretions by the bulbovestibular (Bartholin’s) glands into the vagina. Emission is under sympathetic
control T11-L2. Stimulate contraction of
smooth muscle walls of glands
to release secretions. Also causes contraction of internal uretheral sphincter in males – prevents retroejaculation
Ejection: Ejection of seminal fluid from the penile urethra (or bulbovestibular
secretions) is achieved by rhythmic contractions of the bulbospongiosus
muscles (somatic pudendal nerve)
Orgasm: associated with pelvic and perineal muscle contractions which the brain percieves as pleasurable. It is followed by a refractory period in males (not the case in females). Oxytocin is released in the hypothalamus - supraoptic and paraventricular nuclei. Oxytocin antagonists block partner preference .
• Following ejaculation, sympathetic nervous system causes vasoconstriction and contraction of smooth muscle of the corpora cavernosa to subside erection. Preapism is when this doesnt happen

Question 11

Discuss the roles of different neurotransmitters in sex

Answer 11

NO- vasodilation of smooth muscle.

Oxytocin- pleasure hormone pruduced during orgasm.

Question 12

Relate the neural control of sexual function to spinal cord injuries

Answer 12

Erection is a spinal cord reflex
– Point and Shoot
• Paraplegic men with spinal
cord injury above S2 have
erectile responses to penile
stimulation
• Paraplegic men with lesions
above T11 may also exhibit
emission
• Ejection depends on intact
nerve supply to internal
urethral sphincter

Question 13

Discuss embryo folding and the importance for body formation.

Answer 13

• Embryo folding occurs longitudinally and laterally. Germ layers fuse as they meet forming several vessels of the body laterally. The longitudinal folding is the consequence of rapid enlargement of the neural tubes. The lateral folding is the result of the enlargement of somites.
• This is essential for creating primitive gut tubes and creating the body cavity. Errors could affect the formation of major organs.

Question 14

Explain gastrulation.

Answer 14

-Week 3: Gastrulation
oThickening forms on embryonic disc= primitive streak
o Mid sagittal dorsal
o Elongates and deepens
o Primitive streak formation signals start of gastrulation, definition of body axis, LR asymmetry established
o D16 the primitive streak cells undergo EMT (elongate and migrate)
o They migrate between the epiblast and hypoblast (embryonic mesoderm)
o They migrate into the hypoblast and replace it (endoderm)
o Remaining epiblast cells become ectoderm

Question 15

Discuss the different types of placenta

Answer 15

Diffuse: Almost the entire surface of the allantochorion is involved in formation of the placenta. Seen in horses and pigs.
Cotyledonary: Multiple, discrete areas of attachment called cotyledons are formed by interaction of patches of allantochorion with endometrium. The fetal portions of this type of placenta are called cotyledons, the maternal contact sites (caruncles), and the cotyledon-caruncle complex a placentome. This type of placentation is observed in ruminants.
Zonary: The placenta takes the form of a complete or incomplete band of tissue surrounding the fetus. Seen in carnivores like dogs and cats, seals, bears, and elephants.
Discoid: A single placenta is formed and is discoid in shape. Seen in primates and rodents.
There are different classification systems used based on which maternal layers are retained in the placenta:
Epitheliochorial: has endometrial epithelium, connective tissue and uterine endometrium (horses, swine, ruminents)
Endotheliochorial- only uterine endothelium (dogs, cats)
Hemochorial- none (humans, rodents)

Question 16

Explain maternal recognition of pregnancy

Answer 16

a process in which some type of signal prevents luteal regression, allowing the corpus luteum to persist and continue to secrete progesterone.
Blastocysts of humans and other primates secrete large quantities of a protein hormone called chorionic gonadotropin (CG), which is very similar to luteinizing hormone. CG binds to luteinizing hormone receptors in the corpus luteum and stimulates continued secretion of progesterone. It may also block signals in the corpus luteum that cause luteal regression.

Question 17

Explain the links between the developing urinary and reproductive systems.

Answer 17

• Urinary & reproductive systems dev in close proximity
• Common embryonic origins
• Share common ducts
• Early components of urinary system adopted by reprod
system during later development

Question 18

Explain the development of the male reproductive system

Answer 18

Week 7 - testis differentiation evident
• SRY gene control – sufficient & vital
• SRY initiates primitive sex cords prolif & form seminiferous cords
• Sertoli cells – AMH from wk 6
• Mesenchyme cells form Leydig cells – secrete T from wk 8
• Testes descend into scrotum through inguinal canals
• Controlled by testosterone & Insl3
Ducts and Glands
• Paramesonephric / Müllerian ducts regress due to AMH from testis
• AMHR expressed in mesenchyme of ducts
• Mesonephric duct loses its urinary function, replaced by
metanephros
• Mesonephric duct → epididymis, ductus deferens & seminal vesicles
• Mesonephric tubules → efferent ducts, connecting seminiferous tubules to
mesonephric duct
• In 3rd mth, prostate & BUG grow from pelvic urethra (from UGS)
Genitals
• androgens cause GT to elongate
into penis
• Genital swellings enlarge & fuse
= scrotum
• Urethral groove closes in male
with fusion of genital folds
(penile raphe)
• Encloses the urethra
6th week urethral groove forms along the ventral surface of Genital
Tubercle
• Androgens - GT elongates to form penis, urethral folds grow toward
one another & fuse in midline
• Begins proximally & extends distally toward glans penis
• Converts to urethral groove into a tubular penile urethra
• Penile urethra is completely enclosed by 14 weeks
• Hypospadias results from failure of formation or fusion of the urethral folds

Question 19

Explain the development of the female reproductive system

Answer 19

• Female the ‘default’ condition?
• After PGCs enter future ovary, remain concentrated in the outer cortex
• Enter meiosis ~wk 20
• Primitive sex cords degenerate & form stroma
• Somatic cells form follicular cells
• origin of the cells that form the ovarian follicles not established
• Active signals required for female development
• Wnt4 knockout mice have no Müllerian ducts
• similar human mutation
Ducts and Glands
Mesonephric duct regresses due to lack of Testosterone
• Müllerian ducts retained due to lack of AMH
• The proximal portions = fallopian tubes
• Fusion of distal portions forms uterus & possibly vagina
• Caudal portion of vagina is thought to develop from UGS
• As ducts fuse, a peritoneal fold forms to give the broad ligament
Genitals
GT → clitoris
• Labioscrotal swellings remain
unfused = labia majora
• Genital folds remain unfused
= labia minora
• UGS remains open = vestibule
• Vagina & urethra open
into this
• Urethral groove remains open
in females

Question 20

Describe common examples of reproductive disorders.

Answer 20

Congenital Adrenal Hyperplasia
- condition which causes an error in the production of cortisol and other steroids in the adrenal glands. Excess androgens are produced. Mutation that effects XX females. Results in internal female sex organs and external male phenotype. Early puberty.
Cryptorchidism
Failure of normal testis descent
– 2nd phase more commonly fails
• commonest congenital malformation (one or both testes), affecting 7-9% of boys
at birth
• important cause of low sperm counts/infertility in adulthood
• Most important risk factor for testis germ cell cancer
• Treatments: GnRH or surgery
Klinefelter Syndrome
47 XXY or mosaic (some cells normal, some aneuploid)
• Trisomy (meiotic non-disjunction of chromosomes)
• Leydig cells do not produce enough T
Symptoms not usually apparent until puberty
– Some males may have none at all
– Often not diagnosed until puberty or adulthood
• Typical features
– tall stature (with disproportionately long legs and arms), pearshaped fat distribution and delayed puberty
– There may be signs of under masculinisation
• small /undescended testes, little body hair & breast dev
– Infertility and lack of libido are also common
• Affects ~ 1 in 600 newborn boys
• Currently no cure
– T replacement may induce a more male appearance & reduce risk
of osteoporosis
• Fertility can often be accomplished with assistance (azoospermia or
oligospermia

Question 21

Discuss the ethical and social implications of diagnosing and ‘treating’ disorders of sexual development

Answer 21

Individuals may have been raised as male and identify as such. They may wish to remain as they are and that is something that doctors must account for.

Question 22

Describe the indifferent stages of sexual development

Answer 22

Derived from
intermediate mesoderm
= urogenital ridge in this
region
Except germ cells
• yolk sac
Primordial germ cells migrate from yolk sac through hindgut into dorsal embryo
• PGCs originate in extraembryonic mesoderm at the posterior end of primitive streak
• Populate area adjacent to coelomic epithelium (=mesothelium = mesodermal epith)
• Coelomic epithelium proliferates in wk 5
• Together with Intermed Mesoderm & PGCs → pair of genital ridges
• Primitive sex cords form - PGCs migrate into them (wk 6) → Indifferent gonad
• Once in gonad, somatic envir controls PGC fate - male or female gametes
Reproductive Ducts
• New pair of ducts form week 6
= müllerian/ paramesonephric ducts
• longitudinal invaginations of coelomic epith
• Just lateral to mesonephric ducts in males & females
• extend to posterior wall of UGS (bladder)
Genitals
Identical until wk 7 – fully differentiated by wk 12
• derived from mesodermal tissue located around the cloaca
• prominent genital tubercle develops - flanked by a pair of genital folds
• Lateral to these are paired genital swellings
• When the original cloacal membrane breaks down during the eighth week,
the UGS opens directly between genital folds
• These structures are virtually identical in male and female embryos during
the indifferent stage
Differentiation begins ~ wk 10-12
• urethral folds form lateral walls
of urethral groove
• Open in males & females at
this stage

Question 23

Describe normal growth and how it is regulated.

Answer 23

Growth is linear but episodic
Tightly regulated and controlled by hormone secretion.
Growth hormone secretion occurs in spikes at different parts of the day.
Can be influenced by Puberty, exercise, drugs, sleep.
Bone growth occurs in several steps at growth plates in bones. Influenced by hormonal signals.
1- formation of bone collor around bone cartilage model
2- cavitisation of cartilage model
3- Invasion of cavities by periosteal bud and spongy bone formation
4- Formation of medullary cavity as osification continues, appearance of secondary ossification centres in epiphysis in preperation for
5- ossification of the epiphysis. When completed hyaline cartilage only exists in the epithyseal plates and articular cartilages.

Hypothalamus releases GHRH which interacts with the anterior pituitary. Releases GH which acts on liver peripheral tissues. LPT release IGF-I protein which acts on growth plates.

Question 24

Describe normal puberty and how it is regulated.

Answer 24

Several factors effect puberty including: genetics, diet, stress, gonadal steroids etc… For example- overweight individuals are more likely to undergo puberty earlier.
Onset when pulsitile release of sex hormones increase. Begin to develop sexual characteristics.

Question 25

Discuss the interaction between sex hormones and growth.

Answer 25

Males and females (rats) have different GH secretion profiles
These profiles change when sex hormones are removed
Part of the explanation for different pubertal growth patterns
in males and females

Question 26

Explain what teratology is and what different organs/ teratogens have different windows of sensitivity.

Answer 26

Teratology is the study of abnormal development and causes of congenital malformations. Enzyme deficiencies causing biochemical problems, Altered histology & physiology, Altered gross anatomical structures, Altered behaviours
Wks 1-2: Teratogens either no effect or miscarriage
• If one or two cells are killed, the embryo can compensate – no effect
• If more cells killed, embryo lost before even knows she was pregnant
– Hard to get figures … ? 60% d2 zygotes abnormal & die
Wks 3-8: Teratogens acting now cause major malformations
• Period when most organs are forming
• Each organ system has its own period of maximum sensitivity
Wks 9-38: Functional deficits, growth disturbance & minor abnormalities
• Generally, too late for structural defects – most organs already formed

Question 27

Discuss different types of teratogenic effects, using specific examples

Answer 27

Too little growth = microcephaly (small head). Too much growth = gigantism of a structure. Too little cell death = syndactyly (fused digits). Too much cell death = patent foramen ovale (hole in heart). Failure of migration e.g organ level = undescended testis. Failure of fusion = cleft lip, cleft palate. Duplication e.g. of intestine. Whole embryo = identical or conjoined twins. Faulty induction = renal agenesis (failure to develop).
Thalidomide induced malformation
- Caused by a drug prescribed for morning sickness (has an unexpected isomer that caused damage to foetal development)
- Causes a variety of severe birth defects
- leprosy, multiple myeloma, and cancers, as well as Crohn’s disease, HIV, and others
- Damage was primarily seen to the limbs (upper limbs more commonly affected than lower limbs), face, eyes, ears, genitalia, and internal organs, including heart, kidney, and gastrointestinal tract. The vertebral column was also affected in some survivors and occurrence of facial palsies was also documented.
Spina Bifida
Most children with spina bifida have some degree of weakness or paralysis in their lower limbs. They may need to use ankle supports or crutches to help them move around. If they have severe paralysis, they’ll need a wheelchair.
Paralysis can also cause other, associated problems. For example, as the muscles in the legs aren’t being used regularly, they can become very weak.
As the muscles support the bones, muscle weakness can affect bone development. This can cause dislocated or deformed joints, bone fractures, misshapen bones and an abnormal curvature of the spine
Can be caused by a lack of folic acid during pregnancy. It is a neural tube defect

Question 28

Compare different anatomy of pelvis, between sexes and species, and its role in birth.

Answer 28

Females have a rounder pelvis inlet gap than males to allow for childbirth. Females – lighter in weight, wider laterally, shorter superiorly to inferiorly, less funnel-shaped; less obvious muscle attachements. The sacrum broader, inferior part directed more posteriorly sacral promontorydoes not project as far anteriorly. Pelvic outlet is broader and shallower. Illeum is shallower and flared laterally. Ischeal spines are further apart. Ischeal tuberosities: Females – turned laterally, Males – Turned medially
The pelvis is unusually narrow to accomodate upright walking. Other species have slightly larger pelvises to accomodate birth (their offspring are born with a greater independence). Human offspring are not independent and if they were to stay to term they would not fit.

Question 29

Explain the metabolic and physiological changes seen during pregnancy.

Answer 29

Progesterone and oestrogen levels cause weekening of the joints, food cravings, constipation, spongy gums can lead to dental issues.
Strain on spine as pregnancy progresses (curvature)

Question 30

Describe the anatomical and physiological processes involved in parturition and birth

Answer 30

Symphysis pubis and other ligaments.
During pregnancy hormones such as relaxin remodel this ligamentous
capsule allowing the pelvic bones to be more flexible for delivery. The gap
of the symphysis pubis, normally is 4–5 mm but during pregnancy there
will be an increase to ~9 mm between the two bones.
Relaxin - protein hormone ~6,000 Da in the insulin superfamily.
Softens the pubic symphysis, relaxes other pelvic ligaments.
Produced mainly by the corpus luteum, in both pregnant and
nonpregnant females.
Contraction of the myometrium – during pregnancy oestrogens induce
hypertrophy and deposition of glycogen - prostaglandins and oxytocin
promote contractions
Softening of the cervix – ‘ripening’ – PGE2a and PGF2a, and possibly nitric
oxide (NO) promote - reduction in collagen fibres, increase in
glycosaminoglycans which decrease aggregation of collagen fibres,
metalloproteinases increase as parturition approaches – influx of
inflammatory cells
Relaxation of the symphysis pubis – relaxin (corpus luteum; may have other
roles in pregnancy)

Question 31

Describe lactation and the constituity of milk

Answer 31

Sequence of hormonal changes
underlying the onset of lactation
in humans. Withdrawal of oestrogen and
progesterone at birth removes
block to prolactin-induced milk
secretion. In pregnancy, prolactin is partly
decidual and partly pituitary in
origin, hence drop in its levels at
parturition.
Humans have many ducts opening to the nipples. Several lactiferous sinuses lead into the nipple in humans. Mammary glands are predicted to provide a lurication function during suckling. Lubules containing alveoli (epithelial cells and myoepithelial cells and lumen with secretory materials).
In early pregnancy oestrogen, progesterone and aldesterone lead to increase in ducts, lobules and alveolar growth. limited milk production due to inhibition of prolactin enzyme in the pituitary.
Late pregnancy and term (37-42 wk) oestrogen and progesterone promote alveolar differentiation. Steroid and prolactin levels high: Steroids begins to fall
leads to colostrum production
Parturaltion- Oestrogen and progesterone fall precipitously. Prolactin levels decline
but basal concentrations remain high. Suckling triggers prolactin release at each feed: synthesis of lipids, milk and lactose.
Milk- released prolactin in ant. pituitary in response to suckling. Colostrum
‘First milk’. Less carbohydrates, lipids, potassium than normal milk. Rich immunoglobulins - IgA, IgG, IgM. Cytokines and chemokines. Innate immune system - lactoferrin, lysozyme, lactoperoxidase, complement, proline-rich polypeptides

Question 32

Define the stages of birth

Answer 32

First stage – begins with onset of contractions, ends when cervix fully dilated
Second stage – Begins at full cervical dilation, ends with delivery.
Third stage – Begins with full expulsion of foetus, ends with expulsion of the
placenta, detachment by contraction of myometria (often ‘managed’ by
administration of oxytocic agents or ergometrine and by steady pulling on
the cord – best left to proceed naturally?)