Reproductive Physiology

Reproductive
Physiology
Lyndsay Creswell
Jack Thompson
Learning Outcomes
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Relevant female anatomy
Relevant male anatomy
Female reproductive physiology
Male reproductive physiology
Physiology of fertilisation
Physiology of labour
Physiology of newborn
Female Internal Anatomy
Female internal anatomy
Uterus: fibromuscular organ divided into 3 layers, the endometrium, myometrium and serosa. Supplied by uterine artery (internal
iliac artery branch). Inferiorly it is continuous with the cervix. Communicates with fallopian tubes at each cornu
Endometrium: complex mucous membrane which undergoes cyclical changes in structure and function in response to ovarian
hormonal stimulation. In the first 14 days the endometrium proliferates; glands thicken and elongate under oestrogen influence
(proliferative phase). In days 14-28, under the influence of progesterone, the glands swell and blood supply increases (secretor
Myometrium: smooth muscle layer, relevant to menstruation and labourCervix: dense fibrous connective tissue, continuous with
the uterus at internal os. The cervical canal opens into the vagina at external os
Fallopian Tubes: 2 tubes which can be divided into: isthmus, ampulla and infundibulum(with fimbriae)
Ovaries: supplied by ovarian artery (abdominal aorta branch). Outer cortex covered by germinal epithelium, contains follicles and
theca cells. Inner medulla contains bv and CT
Oogenesis
(Simply: diploid cell -> haploid cell)
The development of mature ova (haploid) from their primitive
precursors: oogonia (diploid)
Oogonia divide by mitosis during fetal life to produce primary oocytes:
approx 1-2 x 10^6, which are present at birth. This is the only source
of the mature ova (22 autosomes and 1 sex chromosome) which begin
to develop from puberty, in contrast with the continuous replication of
spermatogonia in post pubertal males. Thus, the so called ‘biological
clock’, particularly as genetic abnormalities accumulate in older
primary occytes (due to genetic ‘mistakes’ during meiosis)
Primary oocytes begin the first meiotic division before birth. All further
development arrests until puberty, when the first meiotic dision is
completed. This produces a cytoplasm and nutrient rich secondary
oocyte (haploid, with 2 copies of each unpaired chromosome) and a
small polar body of chromosomal material.
Formation of the secondary oocyte is delayed until just prior to
ovulation, (stimulated by LH surge) and the secondary oocyte only
completes its second meiotic division if it is fertilised.
Hypothalamus-pituitary-ovarian axis
Hypothalamus located at base of the brain: acts as central processing unit of the
reproductive system: neuronal stimuli from the cerebral cortex are converted by the
hypothalmus into pulses of gonadotrophin releasing hormone (GnRH). At the end of
the menstrual cycle, oestrogen levels are low, stimulating GnRH release.
The pituitary gland’s anterior lobe secretes luteinising hormone (LH) and follicle
stimulating hormone (FSH) which are also known as GONADOTROPHINS. They
are released under the influence of GnRH.
FSH stimulates follicular development by activating granulosa cell division and
secretion of oestrogen. The increasing amount of oestrogen produced by the
developing follicles act to reduce GnRH and gonadotrophin levels by negative
feedback; such that only one follicle, the dominant or graafian follicle can ovulate.
LH has 3 known functions: 1. It stimulates theca cells, and thus the secretion of
androgens, which act as precursors for the synthesis of oestrogens.
2. LH also triggers ovulation of the dominant follicle. This is known as the ‘LH
surge’, when suddenly, increasing oestrogen levels trigger a positive feedback
mechanism, causing a surge in LH and FSH, and thus ovulation.
3. Additionally, LH stimulates luteinisation of the follicular remnants to form the
corpus luteum, which secretes oestrogen and progesterone to support the
endometrium, and the potential developing embryo.
Oestrogen and Progesterone
Oestrogen
Progesterone
Secondary sexual characteristics
-thelarche (breast development)
-adrenarche (axillary and pubic hair
development)
Menstrual cycle: induces formation of
secretory endometrium during which the
glands become saw toothed and tortuous,
producing glycogen suitable for implantation
Menstrual cycle: development of mature
dominant follicle and ovulation, and
preparation of proliferative endometrium
Induces lobuloalveolar maturation of the
breasts in conjunction with prolactin during
pregnancy to allow for milk production and
lactation
Bone protection
Promotes conditions in utero suitable for
pregnancy
Duct growth of breasts in pregnancy
Thickens cervical mucus
Promotes conditions in utero suitable for
pregnancy
Menstrual Cycle
Menstrual Cycle
Days 1-4: Menstruation. The endometrium is shed as hormonal support is
withdrawn. Myometrial contraction, which can be painful also occurs to expel
the endometrial lining.
Days 5-13: Proliferative Phase.
-Oestrogen and progesterone concentration falls
-Pulses of GnRH from hypothalamus increase, stimulating release of FSH and
LH inducing follicular growth
-Oestrogen and progesterone levels rise, thus suppressing the gonadotrophins
by negative feedback such that only one dominant follicle matures from a
number of primordial follicles.
-However, as oestrogen continues to rise, a switch to a positive feedback loop
on the hypothalamus and pituitary causes an LH surge, stimulating ovulation.
The high oestrogen causes the endometrium to become proliferative, and the
glands to proliferate.
Days 14-28: secretory/luteal phase
-Formation of the corpus luteum : the granulosa and theca cells of the ovary
become swollen by fat droplets, and the structure becomes more vascular.
-The corpus luteum secretes oestrogen, but significantly more progesterone.
This induces secretory changes in the endometrium, to support an implanted
embryo. If the oocyte is not fertilised, the lack of placental b-hcg to support the
corpus luteum causes it to fail, and hormonal withdrawal. The endometrium
thus breaks down in menstruation, and the cycle starts again.
Functional anatomy- Male
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Testes
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Seminal vesicle
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Contributes to 30% of semen production and creates
alkalinity of semen
Epididymis
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Contributes to 70% of semen production and
importantly provides fructose
Prostate gland
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Exo and endocrine function
Production of testosterone and spermatogenesis
Storage and maturation of spermatozoa
Vas deferens
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Causes propulsive force of spermatozoa into the
ejaculatory duct where it mixes with semen before
ejaculation
Spermatogenesis
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Spermatogenesis occurs in the
seminiferous tubules which are
found in the testes.
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Spermatids are deposited in the
lumen of the seminiferous
tubules to undergo maturation
into spermatozoa
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The most mature cells are then
stored in the epididymis
Spermatogenesis
2n
● Spermatogonia
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2n - 46 Chromosomes
Produced from stem cell
Undergoes mitotic division
4n
4n
● 1o Spermatocytes
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2n
4n - 46 Paired Ch
Undergoes meiotic division
2n
● 2o Spermatocytes
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2n - 23 Paired Ch
Undergoes further meiotic division
n
n
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● Spermatids
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n - 23 Unpaired Ch
Undergoes maturation known as spermiogenesis
● Spermatozoa
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n - 23 Ch
Further maturation (addition of mitochondria and flagellation
Fertilisation
-Following ovulation the ovum is propelled by the movement of the cilia lining the fimbriae and
fallopian tube.
-Spermatozoa must penetrate the mucus of the vagina to fertilise the ovum; this occurs at
ovulation when the ratio of oestrogen to progesterone is at its peak, and the mucus is thinner
and less dense
-The uterus contracts to aid spermatozoa motility to the fallopian tubes
-The fallopian tubes contract by retrograde peristalsis to increase chances of fertilisation
-300 X 10^6 spermatozoa per ejaculate
-fertilising ability of the sperm is enhanced following several hours exposure to the female
reproductive tract: this process is ‘capacitation’
-Fertilisation requires the sperm to penetrate the corona radiata and zona pellucida which
surround the ovum.
This is aided by 1) sperm motility to force their way between granulosa cells of corona radiata
2) digestive acrosomal enzymes
When the first spermatozoa contacts the plasma membrane of the secondary oocyte, the
zona pellucida changes chemically, becomig impermeable to other sperm. This completes the
2nd meiotic division, and a diploid zygote is formed.
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Implantation
-Once the diploid embryo is formed, mitotic division begins, forming a solid
ball of cells, the ‘morula’ at days 3-4
-The morula is transported towards the uterus by peristalsis and action of the
cilia within the fallopian tube. It reaches the uterus by day 3-4
-Day6-8, the blastocyst is formed, consisting of:
1. An outer shell of trophoblasts (fetal part of placenta)
2. Fluid filled blastocoele which forms the yolk sac
3. Inner cell mass (from which all embryonic structures develop
In the first 7-10 days the morula, and then blastocyst is nourished by the
secretory endometrium. Further development requires implantation of the
blastocyst by the trophoblast layer. The trophoblast layer adheres to the
endometrial surface, then digests it, extending like ‘finger like processes’ into
the cavities formed by digestion. The endometrium becomes more vascular
by the release of prostaglandins, enhancing the nutrient content, and
importantly, forming the decidua..
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the blastocyst is fully buried within the decidual endometrium by days
10-12
Placenta
-nutrient and gas exchange
-removal of fetal waste products by diffusion into
maternal blood
-partial protection from teratogens and infectious
agents in maternal circulation
-endocrine function, including secreting oestrogen
and progesterone
NB soon after implantation, the chorion of the
developing placenta secretes b-hcg (human
chorionic gonadotropin), which acts on the corpus
luteum to prevent its regression. Thus oestrogen
and progesterone production from the CL continues
until the placenta becomes the chief source of sex
hormones from approx 3 months into the pregnancy
Placental Development
-After the first few weeks, the nutritional needs of the embryo cannot be met by cannibalisation of the
maternal tissue.
-The placenta must develop to sustain the developing foetus
-A membrane derived from the trophoblasts (fetal component), the chorion, erodes the maternal
capillaries of the decidua. More blood filled spaces develop, into which the chorion’s finger like
processes will project. eventually forming placental villi.
-Fetal blood from umbilical arteries (deoxygenated) is circulated through the chorionic capillaries
within these villi (site of fetal-maternal exchnage) and is then recirculated by the umbilical vein
(oxygenated).
-By week 5, the placenta is well established with both fetal (chorionic) and maternal (decidual)
components
-The maternal and fetal blood are separated by chorionic tissue and capillary endothelium. this
provides a protective barrier and allows necessary exchange.
Labour
● Should normally occur at 40 weeks of gestation
● It is split into 3 stages:
o 1st stage - Onset of contractions until full cervical dilatation
o 2nd stage - Full cervical dilatation to birth of child
o 3rd stage - Delivery of placenta
Labour
● 1st stage (3-24 hrs)
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Dilatation of the cervix up to 10cm
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This occurs as the baby’s head descends and causes release of
oxytocin from the posterior pituitary
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Oxytocin driven with positive feedback loop causes contraction
that increase with time
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Prostaglandins also cause uterine contraction
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Relaxin softens connective tissue to ease passage of baby
● 2nd stage (30-120 mins)
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Delivery of baby through vaginal tract with the aid of abdominal
and cervical muscle contraction
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No longer than 2 hours in nulliparous and 1 hour in multiparous
● 3rd stage (15-30 mins)
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Delivery of placenta
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Essential that entirety of placenta is evacuated
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Followed by uterine contraction and
Oxytocin
Myometrial contraction
Cervical stretch
Spinal afferents
Hypothalamus
Post. pituitary
Lactation
● Breast development throughout pregnancy
o Oestrogen - Stimulates duct growth
o Progesterone - Promotes lobule growth
o Prolactin & Human Chorionic Somatomammotropin - Stimulate the
synthesis of enzymes necessary for milk production
● After pregnancy:
o Drop in steroid levels
o Suckling reflex stimulates milk production due to release of prolactin
from ant. pituitary
o Release of oxytocin from post. pituitary stimulates myoepithelial cell
contraction leading to milk ejection from the ducts
o Prolactin release also has a contraceptive role
Newborn cardiac changes
● Fetal shunts:
o Ductus Venosus
o Foramen Ovales
o Ductus Arteriosus
● Changes at birth
o ↓Placental circulation→ ↑TPR→ ↑Aorta→ ↑LV→ ↑LA
o Pulm expansion→ ↑Pulm oxygenation→Pulm v.dilat→ ↓Pulm
resistance→ ↓Pulm Trunk→ ↓RV→ ↓RA
o R→L shunt moves to L→R and closes foramen ovales
o Closure of Ductus Arteriosus happens within 1-8 days
o Closure of Ductus Venosus happens within 1-3 hours