PHYSIOLOGY OF REPRODUCTION
Life is a dynamic system with focused behavior, with
autoreproduction, characterized by flow of substrates,
energies and information.
Reproduction in mammals (humans):
1) Sexual reproduction
2) Selection of partners
3) Fertilization is internal
4) Viviparity
5) Eggs, resp. embryos – smaller, less, slow development, placenta
6) Low number of offspring, intensive parental care
In humans – high investment, low-volume reproduction strategy.
Reproduction in humans – gender comparison:
1) Both male and female are born immature (physically and sexually)
2) Sex hormones production in men also during prenatal and perinatal periods, not
in women!
3) Reproduction period significantly different – puberty, climacterical
4) Character of hormonal changes significantly different – cyclic vs. non-cyclic
INDIFF. GONADE week
XY XX 6.
medulla cortex
SERTOLI CELLS CELOM GRANULOSIS 7.
LEYDIG CELLS MESENCHYME THECA 8.
SPERMATOGONIA GERM.EPITH. OOGONIA 9.
AMH
m W M w 10.
T
Shift of programme
SEX DIFFERENTIATION
Non-disjunction, mosaic. Examination (amniocenthesis, biopsy of chorioid.tissue).
Genetic male Genetic female
testes-determining gene
Wolf duct
(epidydimis, vas deferens)
Muler duct (tuba uterina, uterus)
AMH!!!
RATIO A/E
T a AMH affects inner reprod.system in unilateral way (inner gene)
AMH (MIH, MIF, MIS) – ANTIMULERIAN HORMONE
1940, TGF-b, receptor with internal tyrosinkinase activity
Source: Sertoli cells (5th prenatal week) or embryonal ovary (36th prenatal
week)
In adult women – granulosa cells of small follicles (NO in antral – under
influence of FSH - and atretic follicles)
Role in men:
• Regression of Muller duct
• marker of central hypogonadism
Role in women:
• Lower plasmatic levels (by one order), till climacterical
• Estimation of ovarian reserve (AMH level corresponds to pool of preantral
follicles)
• marker of ovarian functions loss (premature climacterical)
• Diagnosing of polycystic ovaria syndrom
TUMOUR MARKER
BIOSYNTHESIS OF STEROID HORMONES
CHOLESTEROL
PREGNENOLON DEHYDROEPIANDROSTERON
PROGESTERON ANDROSTERON
CORTIKOSTERON TESTOSTERON
CORTIZOL
ALDOSTERON ESTRADIOL
ACTH
LH
LH
AT II.
FSH
chol.desmolase 17-a-hydroxylase
3-b-dehydrogenase
21-b,11-b-hydroxylase
ald.synthase aromatase
cortex of suprarenal glands gonads
PUBERTY
DHT
(5a-reductase)(inhibition-treatment of alopecia)
(lack in hermaphrodites; inhibition-treatment of endometriosis)
Impact of androgens on CNS.
CONTROL OF SEX HORMONES SECRETION
HYPOTHALAMUS
ADENOHYPOPHYSIS
GONADS
GnRH
dopamine endorphins noradrenalin
FSH LH
activin
inhibin
n.arcuatus
gonadoliberine (decapeptid)
E P T
PROLACTIN
Prepubertal nervous blockade of GnRH
Blockade of effect
Down-regulation of LH
receptors in testes and ovaria
PROLACTIN
• Protein, 199 AA, Mr = 22 500
• Lactotrophic cells of adenohypophysis
• Glycosylation = regulation of activity
• Mostly inhibitory effect of hypothalamus on PRL synthesis
• Stimulatory effect of thyreoliberin and VIP peptide, but also estrogens
• During gravidity - PRL levels increase by 20-times, during lactation its release is stimulated from
mammal mechanoreceptors
• In men: approx. half levels as compared to women (5 ng.ml-1 vs. 8 ng.ml-1)
• Released during sleep (continually), during stress, exercise
• Laktotrophic effect:
– Stimulation of mamma differentiation in puberty
– Growth of mamma during pregnancy (together with estrogens and progesterone)
– Stimulation of casein and lactalbumin synthesis
• In men: effect on testosterone metabolism and androgen receptors synthesis
• Released during orgasms, caused temporary decrease of libido
• Minor effects on immune functions
• High PRP levels = amenorrhea, anovulation with galactorrhea (in women), in men – decrease of
libido, impotence, oligospermia, decreased testosterone production
Co-hormone
LEPTIN A REPRODUCTIVE FUNCTIONS
Activation of reproductive system does not depend on age, but on nutritional state of organism.
LEPTIN: ob-protein, ob-gen, 7.chromosome
„leptos“ = thin, slim
polypeptide, 176 AA
Bound in hypothalamus: n.paraventricularis, suprachiasmaticus, arcuatus a
dorsomedialis
Produced in: adipocytes, placenta, stomach, mammal epithelium (???)
Leptin plasmatic levels are sex-dependent (less in males) and do not depend on
nutritional state
Leptin receptor: gene on 4.chromosome, 5 types of receptor, A-E
Receptor B – effect in gonads and hypophysis
Leptin is not only a factor of body fat amount, but affects also the regulation of
neuroendocrine functions including hypothalamo-hypophyseo-gonadal axis.
ncl. arcuatus
area preoptica - reproduction
???Critical amount of adipose tissue – leptin – hypothalamus – LHRH - puberty
Effects of leptin on testes are not elucidated yet.
Testosterone and dihydrotestosterone suppress production of leptin in adipocytes!
REGULATION OF PUBERTY ONSET BY LEPTIN
Critical body mass.
Leptin plasmatic levels in pre-pubertal children are sex-independent.
Pre-pubertal „leptin resistance“ (relative).
In puberty, girls produce 2x more leptin per 1kg of adipose tissue than boys.
Puberty
•Telarche
•Pubarche
•Menarche
•Adrenarche
Pubertas praecox (central)
Pseudopubertas praecox (peripheral)
CRITICAL DEVELOPMENTAL PERIODS
1) Birth
2) Weaning
3) Puberty (adolescence)
4) Climacterical (menopause)
Late puberty
isosexual
heterosexual
Pinilla et al., Phys Rev 92: 1235- 1316, 2012
CONTROL OF SEX
HORMONES SECRETION
MALE REPRODUCTION SYSTEM
TESTOSTERON PRODUCTION:
•Embryonic – sex differentiation, development of generative organs
•Perinatal – descensus testis (?)
•Fertile period – LH pulsation
•After 50.year – decrease of sensitivity to LH
FSH LH
SERTOLI CELLS LEYDIG CELLS
INHIBIN TESTOSTERON
MIS
ACTIVIN DHT
ABG
aromatase
GnRH
glycoproteins
HUMOURAL CONTROL OF REPRODUCTIVE FUNCTIONS IN MAN
-
-
-
PROLAKTIN
5a-reductase
SPERMATOGENESIS
Leydig cell
Capillary
Basal membrane
Spermatogonium
Tight junction
Spermatocyte
Spermatide (haploid)
Sertoli cell (contraction)
Spermia
70 days
1-64 (6 divisions)
Temperature<35°C
Acrosom (enzymes)
Head (nucleus, DNA)
Body (mitochondria)
Flagella (microtubules, 9+2)
Lumen:
androg., estrog.
K+
glutamate, aspartate
inositol
PRODUCTION OF SPERM
SEMINIFEROUS TUBULES
SPERMATOGONIA SPERM 2 months
SERTOLI CELLS ABG temperature
LEYDIG CELLS radiation
EPIDYDIMIS maturing, motility 14-21 days
VAS DEFERENS storing months
SPERMATOCYSTS fructose
fibrinogen
prostaglandins
PROSTATE Ca2+, profibrinolysin
SPERM
T
Ejaculation:
3-4 ml
108 sp / ml (season)
pH = 7.5
motility (3mm/min)
Relaxin – improves motility of spermatogonia
Relaxin
FSH
FSH
LH
Volume 1,5 - 2,0
pH 7,2 - 8,0
Concentration of sperm 20 mil/ml
Total number of sperm 40 mil and more
Motility 50% and more in category A+B, above 25% in A
Morphology 30% and more of normal forms
Vitality 75% and more of living sperm
Leukocytes up to l mil/ml
Autoaglutination < 2 (scale 0 - 3)
SEXUAL REFLEXES
CNS cortex, limb.system sexual behaviour
sexual agitation
nn.pudendales mechanoreceptors stimulation
nn.erigentes corpus cavernosum erection
gl.bulbourethralis lubrication
pl.pelvicus epidydimis, vas def.
sem.ves., prostate emission
m.bulbocavernosus ejaculation
trigonum vesicae ur. constriction
PARASYMP.
SYMP.
Sacral
spinal
cord
(glans penis)
(Ach, VIP)