Reproductive Physiology

 Sexual differentiation
 Male reproductive system
 Female reproductive system

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Significance of Reproductive System:

• Has no homeostatic role

Procreation: maintenance of the species
Recreational and Relational

• Types
A. Asexual: Binary fission, budding....
B. Sexual: Genetic diversity by shuffling of genes in
meiosis, crossing-over
and fertilization

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Sexual differentiation
Sex is the physiological and psychological processes
within an individual prompting behavior related to
procreation and/or erotic pleasure.

• Chromosomes in
humans: 46
---22pairs of autosomes
plus an XX/XY
• Sex chromosomes
(XX or XY)
• Autosome/somatic
chromosomes
o 22 pairs
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 Sex types
1. Chromosomal/ Genetic/ Nuclear sex
o XX or XY state of chromosome at the time of fertilization
o Genotype of the sperm  chromosomal sex of the zygote.
44 + XX  Female
44 + XY  Male
 Testis determining gene (TDG) on Y –chromosome = SRY gene
(Maleness)

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2.Gonadal Sex
• Determined by chromosomal sex.
• Differentiation of the primary gonad into Testis or ovary
==================
• 6th week: the gonadal ridge is bipotential.
• 7th week:
a) If SRY gene present, medula develops into testis & cortex
regresses
o Leydig and sertoli cells appear and testosterone and mullerian
inhibiting substance (MIS)are secreted respectively .
b) If no Y chromosome (SRY gene), the cortex develops into
ovaries
by default.

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 3. Genital = Phenotypic Sex
o Hormonally determined (+/- AMH, testosterone, DHT)

1. Internal duct differentiation (ductal sex)

 Wolffian duct into male ejaculatory system (epididymis,
vas deferens, ejaculatory duct, and seminal vesicles)
= 8 – 13 weeks, Testosterone needed
 Mullerian duct degenerates (AMH needed
2. External genitalia (~ term, T  DHT)
• Targets contain 5α reductase (T  DHT)
• The testes will ultimately descend to the scrotum,
stimulated to do so by testosterone (near birth)

The male is an induced sex whereas the female is a default sex

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 THE PHYSIOLOGY OF MALE REPRODUCTIVE
SYSTEM

Three major Male Reproductive Functions

 Sex hormone secretion: Testes
 Sperm production: Testes
 Sperm transport to the female: Ejaculatory duct & Penis

The Male Reproductive Organs (Primary sexual

characteristics):
 Testes, epididymis, vas deferens, ejaculatory duct, seminal
vesicle, prostate, bulbourethral gland, penis
 Promote development, preservation, and delivery of sperm.

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Seminiferous tubules, network of ducts-site of
spermatogenesis which open into the rete testes.
 Interstitial cells of Leydig - secret testosterone
 Sertoli cells – nurse cells
 Germinal cells - Spermatogonia
 Epididymis -where ducts drain into Vas deferens.
 Ejaculatory ducts - which drain into prostate and urethra.
Main functions:
Storage
Maturation of spermatozoa (motility +
fertility)

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 Anatomical adjustments of testes:

Positioned in the scrotum (7th – 9th months, transinguinal

descent.
If not, cryptorchidism)
 32˚C – Optimum for spermatogenesis.
 Periscrotal air circulation
 Scrotal reflex: Dartos + cremasteric muscles
 Sweat glands
 Subcutaneous fat

High Temps-e.g. cryptorchidism-degeneration leading to sterility.

 Hot baths , tight under clothing -reduces sperm count.
 There is improved sperm count in winter as compared to summer
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 Sertoli cells/Sustenacular cells
 During spermatogenesis they render
o Mechanical support , initiate meiosis
o Secret a watery, solute and glycogen-rich fluid
• Spermiation (= release of sperm cells into lumen)
o Form Blood-Testis-Barrier (formed during puberty)
 Secrete MDIH, MIF, ABP, Inhibin, activin, transferrin and
Plasminogen activator and synthesize estradiol (via
aromatase)

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 Spermatogenesis

Genesis site: Seminiferous tubules

 Onset: > 13 years of age (during puberty and never ceases)
 Duration: Spermatogonium → Spermatozoan (70 - 80
days)
Sperm < 35 million /ml semen → fertility impaired
 Transport: 12-21days
 Daily production:100-200 million sperms/d
 Sperm count: 40x106 spermatozoa per ejaculate or more

(ejaculate volume: 3 – 5 cc)

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Processes/Phases of Spermatogenesis: 3
Proliferative phase (Spermatocytogenesis -)
Spermatogonia A→ 1° spermatocyte (mitosis, diploid )
2. Growth phase (Meiosis)
1° spermatocytes → 2° spermatocytes(meiosis I, haploid)
3. Maturation phase (Spermiogenesis)
2° spermatocytes →Spermatids (meiosis II, haploid )
Spermatids mature into spermatozoa (spermiogenesis).

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Extraneous factors affecting spermatogenesis

Temperature: Optimum T°: 33 - 35°C

 X-irradiation:
 Chronic malnutrition:
 Avitaminosis: Vitamin A, B12 & folic acid deficiency
 Chronic illnesses
 Drugs & toxins: Inhibit replication of spermatogonim.
 Alcohol:
 ↑aromatase activity ↓ GnRH (↑ feminization signs)
 Marihuana (Cannabinoids)
 ↓ Spermatogenesis (↓Testosterone synt, ↓ sperm)

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 Puberty/Adolescence
Transition from juvenile to adulthood (able to procreate).
o Physiologic & psychologic changes
Onset: variable
 Boys: 9-14 years
 Girls: 8-13 years
 Range: 8-20 years
Features:
o Adolescent growth spurt
o Secondary sexual characteristics (fat distribution ,...)
o Fertility (spermatogenesis, thelarche, pubarche, menarche)
o Profound psychological changes

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Pulsatile Secretion of GnRH, FSH & LH
The primary event at puberty is increased activity of
hypothalamic pulse generator (↑↑ nocturnal melatonin
→ pulsatile GnRH).
• Modulators: leptin (energy balance), photoperiod
o It drives a parallel pulsatile secretion of FSH and LH
• It depends on genetics, nutrition and stress
• It occurs just before physical changes at puberty.
• Tonic (in males) & Cyclic, +ve feedback (females)

Adrenarche: occurs before the activation of H-H-G (gonadarche). The

adrenal androgens (DHEA, DHEAS) stimulate the growth of pubic and
axillary hair.
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The Biological Effects of Androgens
Fetal period/Prenatal/Prepubertal
o Stimulates development of Wolffian duct system.
o Masculinize external genitalia.
o Descent of testes (near/at birth)
o Establishes male pattern of pulsatile release of GnRH
Pubertal
 Maintenance of secondary sexual characteristics
Bone: ↑T →↑ Protein synthesis →↑ bone matrix → ↑bone
growth → ↑ linear growth
 Skeletal muscle: Anabolic
 Erythropoiesis: ↑ Epo
 CNS: Stimulates libido & behavioral effects
 Integumentary system: ↑ sebaceous → acne, thick
 Metabolism: ↑ BMR
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Sources of seminal plasma (Accessory glands)

1. Seminal vesicles
• Secretions: Yellowish viscous (60 – 75% of semen)
• Fructose, Vit. C/Ascorbic Acid, citric acid: energy source
• Prostaglandins: cervical mucus more receptive to sperm and
↑Uterine motility /sperm transport
2. Prostate gland (largest, ~30%, whitish and clear fluid)
Clot semen in vagina and then liquefy ( 15 – 30 minutes after ejaculation)
Phosphates and Bicarbonates act as buffers (pH ~ 6.5).
-Neutralize acid medium of vaginal secretions
-↑Motility and fertilizing potential of sperm cells
3. Bulbourethral/Cowper’s Glands: (5%, mucus)
“pre-ejaculatory fluid” - flushes urethra, lubricant and
buffers.
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 Semen Analysis (spermatogram)

Ejaculate volume: 3 – 5 cc after several days of abstinence.

 Viscosity : liquefaction in 1 hr
 Sperm density: 50 - 120 million sperm cells/cc (euspermia)
 Sperm lifespan after ejaculation = 24-72 h at 37°C
 Motility: > 50% forward progression within 60 min of ejaculation
 Morphology: > 60% normal

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 Female Reproductive

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Significances:
1. Gametogenic - oogenesis
2. Endocrinologic - hormonogenesis
3. Site of fertilization
4. Pregnancy - nurture & protection of the fertilized ovum.
5. Birth/labor
6. Lactation

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Oogenesis
 Formation of haploid ova
in the ovary
 Steps
• Reduction division -
meiosis I (haploid)
• Equatorial division -
meiosis II
• Maturation – potential
for fertilization

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The Biology of Oogenesis/Folliculogenesis & its control

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Menstrual Cycle & Hormonal control
Monthly cycle of mainly Ovarian & Uterine changes in primates,
overt sign of which is bleeding from the genital tract.
 Variable(range = 20-35d, average = 28d)
 Purpose: Periodic preparation for fertilization & pregnancy.
 Components: Ovarian and uterine cycles

The fertility of the mature human female is cyclic.

Ovarian cycle Uterine Cycle

• Follicular phase • Proliferative phase
• Ovulatory • Secretory phase
• Luteal phase • Menstrual phase
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 Ovarian cycle
Follicular (Preovulatory = Estrogenic) phase
o 1st to 13th day (Variable length, low FSH requirement)
o A process of selection of a follicle.
o Follicular growth & maturation
II. Ovulatory Phase
• 14th to 15th day ≈ 36 hrs

Markers of ovulation:
 Mittelschmerz: mid-abdominal pain
 Spinnbarkheit: ↑ elasticity of cervical mucus
 Ferning pattern and ↑ body temperature ( 0.5oC)

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 Part III

Preantral follicles

Antral follicle

Preovulatory/
Periovulatory

The maturation of the ovarian follicle

34
III. Luteal (Postovulatory = Progestational) phase
 15th – 28th day
 The duration is constant: 14±2d →CL
 Formation of glandular structure called the corpus
luteum.
 Predominant Hormone: Progesterone

What is the fate of corpus luteum?

 No pregnancy: CL degenerates, and shrinks (corpus albicans).
 Yes pregnancy: corpus luteum continues (P) for 10 weeks from
ovulation until the placenta takes over (if inadequate = abortion)

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 Uterine cycle
 Cyclical changes in the uterus mainly in the endometrium.
1. Proliferative Phase = Uterotropic

o Estrogen - Begins with last days of menses (5th to 13th d)

o ↑ mitosis of stratum basale which regenerates stratum functionale
o ↑Straight glandular formation (+ glycogen)
o Cervical epithelium secrets a watery mucus
o Angiogenesis: lengthening of the vessels, neovascularization
o ↑ Estrogen & Progesterone receptors

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2. Secretory Phase

14th - 28th day (~ 14 days long).

o Predominant hormone: Progesterone (+ Estrogen)
o Secretory changes in endometrium →for implantation,
vascularized and edematous
• Mucous glands (torturous): Elongation & coiling, secrete
clear, thick viscous fluid containing glycogen
• Cervical mucus becomes thick
• Angiogenesis: Spiraling of the blood vessels, ↑ vascularity
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 3. Menstrual Phase

Regression of corpus luteum leads to loss of hormonal

support of endometrium .
o Stratum functionale sloughed off.
o Duration: 1-4 d, begins with the first day of menstruation
o Loss of 25 – 35 ml of blood
o Type of blood flow: 75% arterial, 25% venous

Contents: tissue debris, Pgs,

Fibrinolysin , tissue debris
No clot formation: (Fibrinolysis,
excessive bleeding → clot
formation).
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H-H-Ovarian Axis
 Negative feedback control
 E and P in large amounts inhibit FSH and LH
 Positive feedback control
  E exerts a positive effect and stimulates LH secretion
 Min time reuirment
  300% for 36hrs or more a brief decline in secretion was followed
by a burst of LH (eg. mid-cycle surge).
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Sperm Transport and Capacitation
A. Transport
o Flagellar movement/ATP
• Vagina → cervix → uterine cavity → uterotubal junction →
isthmus → ampullary - isthmic junction.
B. Capacitation
o Freshly ejaculated sperm develop capacity to fertilize an oocyte.
• Occurs in the female reproductive tract - within few hrs.

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C. Acrosomal reaction
 Binding to Zona Pellucida → acrosomal reaction
 ZP acts as a barrier to fertilization across species
 Penetration thru Zona Pellucida → 15-25min.

D. Cortical Reaction
 The egg-cortical reaction → block to polyspermy
• Cortical granules released and cortex hardened →
secondary block to polyspermy

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 E. Nuclear Reaction
• Penetration of the sperm into the ovum Secondary oocyte →
Only one mature ovum, 2 polar body/degenerate
Male pronucleus
+
female pronucleus
↓
diploid zygote:
GENOME OF A NEW
ORGANISM MITOTIC
PROCESS will continue

Multiple births may be monozygotic or dizygotic, or a

combination
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of both (dizygotic twins, tripletes, or quadruplets).
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The Endocrine Placenta
Placenta
o Functions: Respiratory, Nutritive, Excretory, Storage & Endocrine
--- Peptide hormones: hCG & hPL
--- ↑ E, P→ ↓ LH & FSH secretion
Human chorionic gonadotropin (hCG)
• Origin: Syncytiotrophoblast
• Secretion and plasma [ ] : 6-8 d after conception

Functions of hCG:
a) Maintain the early corpus luteum of pregnancy
b) Promote steroidogenesis (E, P)
c) ↑ vascular permeability and swelling of the endometrium.
d) Give immunological privilege to the developing trophoblast
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Placental Hormones

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 Human Placental Lactogen (HPL)
 Human chorionic somatomammotropin (hCS)

Acts like as a maternal growth hormone of pregnancy.

 Secretion & Plasma [ ]: 3rd week after conception
 Nature: Lactogenic activity (major) & growth promoting
• Stimulation of lipolysis → ↑ free FA
• Inhibits glucose uptake in the mother → Insulin resistance
• Inhibition of gluconeogenesis →↑ transportation of glucose
& protein to the fetus.

Functions of progesterone
• Inhibits smooth muscle contractility → myometrial
quiescence → prevents premature expulsion of fetus
• Secretory
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 Functions of estrogen
 Fine tune events leading to parturition
 (+) Pg synthesis

Synthetic blockers of the progesterone receptor (mifepristone)

induces early abortion by removing the positive progesterone effects on
conceptus.

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 Parturition
Delivery of the baby.
 Duration of gestation: Humans: 40wks (~270 days, day of LMP or
266 days from time of conception)
 Distension of the uterus
 ↑ Secretion of oxytocin
 Progesterone withdrawal
 ↑Estrogen
 ↑ prostaglandin synthase →↑ myometrial contractions
 ↑ oxytocin , gap junction and actin-myosin
 Oxytocin
 Relaxin
 Relaxes the pubic ligaments & lower uterus.
 Ripen (soften) cervix

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The Mammary Glands and Lactation
Pregnancy: secretion of milk does not occur (inhibition from E & P)
 On expulsion of placenta, ↓ E + P levels initiating lactation.
 It takes 1-3 days for milk to “come in”.
 Suckling evokes reflex oxytocin release and milk ejection
 Colostrum ~ first milk rich in protein (mainly globulins) and salts
 Lactogenesis and maintenance of milk production (galactopoiesis)
require PRL in the presence of insulin, cortisol & T3/T4 (permissive)

Lactation and Menstrual Cycle = lactational amenorrhea

 Mothers do not nurse → menses (6 weeks after delivery)
 Regular nursing→ Amenorrhoeic (25-30 wks)
 50% of the cycles of first 6 months → anovulatory
 Prolactin inhibits GnRH = "nature's contraceptive,"

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 Milk secretion Reflex

Suckling of nipples (mechanoreceptors)

↓
Hypothalamic nuclei
Inhibition of PIH (dopamine) secretion
↓
Secretion of PRL from the anterior pituitary
↓
Stimulation of milk secretion by the mammary glands

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 Milk Ejection Reflex
Nipples (Mechanoreceptors →
suckling) + Auditory stimuli
↓↓
Hypothalamic nuclei (SON, PVN)
↓
Oxytocin released
↓↓
Contraction of myoepithelial cells
surround alveoli and ducts
↓
Mobilizes milk from the alveoli and
duct system to the nipple
↓
Milk -let down

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 Menopause
Climacteric - reproductive cyclicity stops (R = 41-54 y)
 12 consecutive months of amenorrhoea
Features
 Loss of follicular development
 ↓ [ Estradiol] → ↑ FSH, ↑LH)
 Thinning of the vaginal mucosa, infection
 Decreased libido, pain during coitus, hot flash, osteoporesis ....

Andropause
 No distinct andropause in men – but as men age, gonadal sensitivity
to LH and androgen production drops. (serum LH & FSH rise).
 Sperm production begins to decline after 50 years , many men can
maintain reproductive function and spermatogenesis throughout life

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