Reproduction, Marie Nováková1 PHYSIOLOGY OF REPRODUCTION 2 Life is a dynamic system with focused behavior, with autoreproduction, characterized by flow of substrates, energy and information. Reproduction, Marie Nováková 3 Reproduction in mammals (humans) 1) Sexual reproduction 2) Selection of partners 3) Internal fertilization 4) Viviparity 5) Eggs, resp. embryos – smaller, less, slow development, placenta 6) Low number of offspring, intensive parental care High investment, low-volume reproduction strategy ! Pregnancy (days) Mouse 20 Rat 23 Rabbit 31 Dog 63 Cat 65 Lion 107 Pig 114 Sheep 149 Human 260 - 275 Cow 285 Rorqual 360 Elephant (Indian) 609 Reproduction, Marie Nováková 4 Reproduction in humans – gender comparison 1) Both male and female are born immature (physically and sexually) 2) Differentiation of reproduction organs during prenatal period 3) Hypothalamus – adenohypophysis – gonads in both gender, the same signals (hormones) 4) Different productin of sex hormones during prenatal and perinatal periods 5) Reproduction period (puberty - menopause) significantly differs 6) Character of hormonal changes significantly differs – cyclic vs. non-cyclic Reproduction, Marie Nováková 5 • Meiosis occurs only in germ cells and gives rise to male and female GAMETES • Fertilization of an oocyte by an X- or Y-bearing sperm establishes the zygote´s GENOTYPIC SEX • Genotypic sex determines differentiation of the indifferent gonad into either an OVARY or a TESTIS • The testis-determining gene is located on the Y chromosome (testis-determining factor, sex-determining region Y) • Genotypic sex determines the GONADAL SEX, which in turn determines PHENOTYPIC SEX (fully established at puberty) • Phenotypic differentiation is modified by endocrine and paracrine signals (testosteron, DHT, AMH) Reproduction, Marie Nováková 6 INDIFFERENT GONAD 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 SEX DIFFERENTIATION Non-disjunction, mosaic. Examination (amniocenthesis, biopsy of chorioid.tissue). Genetic male Genetic female testes-determining gene (SRY) Wolffian duct (epidydimis, vas deferens) Mullerian duct (tuba uterina, uterus) AMH!!! RATIO A/E T a AMH affect internal genitalia in unilateral way (inner gene) Reproduction, Marie Nováková 7 AMH (MIH, MIF, MIS, MRF) – ANTIMŰLLERIAN HORMONE 1940, TGF-b, receptor with internal TK 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 müllerian duct • Marker of central hypogonadism Role in women: • Lower plasmatic levels (by one order), till menopause • Estimation of ovarian reserve (AMH level corresponds to pool of pre-antral follicles) • Marker of ovarian functions loss (premature menopause) • Diagnosing of polycystic ovaria syndrome TUMOUR MARKER Reproduction, Marie Nováková 8 CRITICAL DEVELOPMENTAL PERIODS Reproduction, Marie Nováková 9 Vybrané kapitoly z fyziologie, GRADA, 2022 Reproduction, Marie Nováková 10 CRITICAL DEVELOPMENTAL PERIODS Late puberty Critical body mass (critical amount of adipose tisssue/nutritional state) Puberty Adrenarche •Pubarche •Gonadarche •Spermarche •Telarche •Pubarche •Menarche Pubertas praecox (central – gonadoliberin-dependent) Pseudopubertas praecox (peripheral - gonadoliberin-independent) Reproduction, Marie Nováková 11 Vybrané kapitoly z fyziologie, GRADA, 2022Reproduction, Marie Nováková 12 Vybrané kapitoly z fyziologie, GRADA, 2022 Reproduction, Marie Nováková 13 LEPTIN AND REPRODUCTION 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, 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. Reproduction, Marie Nováková 14 Effects of leptin on testes are not fully elucidated yet. Testosterone and dihydrotestosterone suppress production of leptin in adipocytes! REGULATION OF PUBERTY ONSET BY LEPTIN Critical body mass (critical nutritional state). 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. Reproduction, Marie Nováková 15 ncl. arcuatus area preoptica - reproduction Critical amount of adipose tissue – leptin – hypothalamus – LHRH – puberty Reproduction, Marie Nováková 16 Pinilla et al., Phys Rev 92: 1235- 1316, 2012 KISSPEPTIN - Increased expression of KISS1 gene - Increased synthesis of kisspeptin - Increased sensitivity of GnRH neurones to kisspeptin - Pulsatory GnRH secretion ……. + - Secretion of GH - Decreased secretion of melatonin PUBERTY ncl. arcuatus - Peptide, 54 AA - Regulation of the puberty onset - Control of GnRH secretion - Produced also in placenta, syncytiotrophoblast, cytotrophoblast, decidua - Released together with neurokinin B and dynorphin Reproduction, Marie Nováková 17 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! Reproduction, Marie Nováková Adrenarche PROLAKTIN 18 GONADOLIBERIN (GnRH, GONADOTROPIN-RELEASING HORMONE) Control of gonadotrophins release - FSH, LH Changed GnRH pulse frequency during the cycle Reproduction, Marie Nováková - Decapeptide, neurones in ncl. arcuatus, inputs from limbic system and other part of CNS related to emotions, smell and stres - Pulsatory secretion (glycosylation) - Receptor coupled to G-protein: gonadotrophs in adenohypophysis, lymphocytes, mamma, ovaries, prostate - (GnRH-I, GnRH-II, (GnRH-III)) - Stimulation of secretion: kisspeptin, dopaminergic system in CNS, leptin - Inhibition of secretion: dominating inhibitory effect of gonadal hormones with exception of estradiol (negative-positive-negative feedback), malnutrition (FA, glu), lactation (PRL), seasonal effect, aging, continual GnRH administration + gonadostatin (neuropeptide suppressing LH, FSH, reproductive functions and behaviour) Acute stress – impairment (of cycle) without effect on fertility Chronic stress – impaired fertility, decreased levels of circulating sex hormones 19 Reproduction, Marie Nováková - Heterodimeric glycoprotein - Subunit alpha common for FSH, LF, TSH, hCG, subunit beta LH specific - Pulsatory secretion - Level of glycosylation affects biological half-time - Structure similar to hCG - Receptor coupled to G-protein: all ovarian cells, Leidig cells, uterus, semenné váčky, prostate, mamma, skin, suprarenal gland, thyroid gland, retina, neuroendocrine cells - Regulation of secretion: GnRH GONADOTROPHINS LUTEINIZING HORMONE (LH) FOLICULES STIMULATIONG HORMONE (FSH) - Heterodimeric glycoprotein - Subunit alpha common for FSH, LF, TSH, hCG, subunit beta FSH specific - Pulsatory secretion - Level of glycosylation affects biological half-time - Receptor coupled to G-protein: granulosa cells, Sertoli cells, endometrium (in secretory phase) - Regulation of secretion: GnRH, oestrogens, activin, inhibin, follistatin 20 ADDITIONAL REGULATION OF GONADOTROPINS SECRETION (LH) Reproduction, Marie Nováková Activins = regulation of transcription Inhibins and follistatin = inhibition of activins by binding on their receptor Produced in gonads and also in CNS, suprarenal glands, medulla. Inhibins – heterodimeric glycoprotein (a + bA or bB) - produced in women in hypophysis, ovaries and placenta, in men in Sertoli cells - negative feedback on FSH production – inhibin A – inhibin B (testes) Activins – dimeric proteins similar to inhibin, activin A, B, AB – stimulation of FSH production – autocrine / paracrine factors – important role in early stages of pregnancy Follistatin – glycoprotein – inhibition of activin - intragonadal autocrine/paracrine regulator - expressed mainly in adenohypophysis 21 FSH and LH - functions FEMALES FSH - Growth and development of follicular cell (maturation) - Biosynthesis of estradiol - Regulation of inhibin synthesis during follicular phase - Upregulation of LH receptors (preovulatory follicles) - Selection of dominant follicle - Recruitment of follicles for next cycle LH - Stimulation of oestrogen synthesis at various levels (theca) - Oocyte maturation (preovulatory follicle) - Rupture of ovulatory follicle, ovulation - Conversion of follicle wall to corpus luteum MALES LH Intratesticular synthesis of testosterone (Leydig cells) FSH Spermatogenesis (Sertoli cells) Reproduction, Marie Nováková 22 PROLACTIN - PRL - Protein - Lactotropic cells (only PRL) - Mammosomatotrophic cells (PRL and GH) - Hyperplasia – pregnancy and lactation - Expression regulated by oestrogens, dopamine, TRH and thyroid gland hormones - PRLR – mamma, adenohypophysis, suprarenal gland, liver, prostate, ovary, testis, small intestine, lungs, myocardium, SNS, lymphocytes Regulation of secretion - Pulsatile secretion: 4 – 14 pulses/day - Highest levels during sleep - Lowest levels between 10:00 and 12:00 - Gradual decrease of secretion during aging - STIMULATION: TRH, serotonin, melatonin, oxytocin + stress, starving, coitus, pregnancy, pharmacological substances - INHIBITION: dopamine Reproduction, Marie Nováková 23 MAIN FUNCTION: Milk production during pregnancy and lactation = „survival“ function PROLAKTIN AFFECTS PRODUCTION OF KISSPEPTIN. Other functions – metabolic, synthesis of melanin, maternal behaviour Breast development a lactation - Puberty – mamma development under the effects of GH a IGF-1 - Effect of oestrogens and progesterone - Age of 8 – 13 - During pregnancy – proliferation of alveoli and proteosynthesis (proteins of milk and colostrum) - During the 3rd trimester – production of colostrum (PRL, oestrogens, progesterone, GH, IGF-1, placental hormones) - Lactation – increase in PRL post-partum, without sucking drop after approx. 7 days - Milk accumulation prevents further PRL secretion Reproductive function of PRL - Lactation = amenorrhea and secondary infertility - Inhibition of GnRH secretion PROLACTIN - functions Reproduction, Marie Nováková 24 REGULATION OF SEX HORMONES SECRETION – simplified scheme HYPOTHALAMUS ADENOHYPOPHYSIS GONADS GnRH dopamine (PIF) opioids noradrenalin FSH LH Activin Inhibin B n.arcuatus gonadoliberin E P T PROLACTIN Pre-pubertal block of GnRH Blocking the effects of gonadotrophins Down-regulation of LH receptors in testes and ovaria Stress Exercise Seasonal variation Nutritional state GABA kisspeptin leptin Reproduction, Marie Nováková 25 MALE REPRODUCTION SYSTEM Reproduction, Marie Nováková 26 TESTOSTERON PRODUCTION: •Embryonic – sex differentiation, development of generative organs •Perinatal – descensus testis (?) •Fertile period – LH pulsation •Ageing – decrease of sensitivity to LH FSH LH SERTOLI CELLS LEYDIG CELLS INHIBIN B TESTOSTERON AMH ACTIVIN DHT ABG Aromatase (conversion of testosterone to estradiol) GnRH glycoproteins HUMOURAL CONTROL OF REPRODUCTIVE FUNCTIONS IN MAN - - - PROLACTIN 5a-reductase Reproduction, Marie Nováková 27 Reproduction, Marie Nováková 28 Reproduction, Marie Nováková 29 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: androgens, estrogens glutamate, aspartate inositol Reproduction, Marie Nováková 30 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 Reproduction, Marie Nováková 31 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) SPERMIOGRAM Reproduction, Marie Nováková 32 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) Reproduction, Marie Nováková 33 FEMALE REPRODUCTION SYSTEM Reproduction, Marie Nováková 34 OOGENESIS DEVELOPMENT 6-8 weeks GERMINAL EPITHELIUM Hormonally OOGONIA FOLLICLE independent mitotic division PRIMORDIAL 24 weeks OOCYTES I. 7 x 106 1. meiosis birth prophase 2 x 106 Hormonally puberty OOCYTES II. 3 x 105 dependent haploid DOMINANT (cyclic) 2. meiosis ATRETIC metaphase GRAAF OVUM OVULATION 2. meiosis – end menopause 0 Reproduction, Marie Nováková 35 Daan and Fauser, Maturitas 82 (2015) 257–265 Reproduction, Marie Nováková 36 Daan and Fauser, Maturitas 82 (2015) 257–265 RECRUITMENT Reproduction, Marie Nováková 37 Pavel Trávník: Klinická fyziologie lidské reprodukce, GRADA, 2022. 290 DAYS 60 DAYS Reproduction, Marie Nováková 38 OVARIAN CYCLE Germinal epithelium Primordial Primary Graaf Corpus haemorrhagicum C. luteum follicle 25m 150m up to 2 cm estradiol progesteron Oocyte-maturation inhibiting factor Vesicular follicle Luteinisation inhibiting factor (estrogens) (progestins) OVULATION methrorhagia Reproduction, Marie Nováková 39 CYCLIC CHANGES ovarian uterine GnRH FSH, LH estradiol basal temper. 0 4 14 28 MENS. PROLIPHER. SECRETORY PHASE + _ 0.5 – 0.75°C FOLICULLAR OV. LUTEAL PHASE 6-10x 2-3x progesteron + vagina/cervix uteri + mamma Reproduction, Marie Nováková 40 Pavel Trávník: Klinická fyziologie lidské reprodukce, GRADA, 2022. A = LH peak B = ovulation FSH estradiol progesteron LH Opioids!!! Reproduction, Marie Nováková 10-12 hrs 41 Pavel Trávník: Klinická fyziologie lidské reprodukce, GRADA, 2022. Granulosaluteine cell Thecaluteine cell androgens estradiol progesterone inhibin A LH Blood capillary Reproduction, Marie Nováková 42 Pavel Trávník: Klinická fyziologie lidské reprodukce, GRADA, 2022. LH basal temperature progesteron A = LH peak B = ovulation Reproduction, Marie Nováková 43 VESICULAR FOLLICLE PRIMARY FOLLICLE - FSH Growth acceleration of primary follicle – change into vesicular follicle: 1) estrogens released into follicle stimulate granul. cells UP REGULATION of FSH receptors and intrinsic positive feedback (higher sensitivity for FSH!!!) 2) UP REGULATION of LH receptors (estrogens and FSH) – another acceleration of growth due to „higher sensitivity“ to LH (positive feedback) 3) Increased estrogens and LH secretion accelerates growth of theca cells, secretion is increased explosive growth of follicle Reproduction, Marie Nováková 44 DOMINANT FOLLICLE 1. High levels of oestrogens from the fastest-growing follicle 2. Negative feedback on FSH production from adenohypophysis 3. Gradual decrease in FSH secretion 4. „Dominant follicle“ continues in growing due to intrinsic positive feedback 5. Other follicles grow slowly and subsequently become atretic Reproduction, Marie Nováková 45 MECHANISMS OF OVULATION LH PROGESTERON Hyperaemia of follicle Secretion of prostaglandins Weakening of follicle wall PROTEOLYTIC ENZYMES (collagenases from theca externa) Degeneration of stigma Rupture of follicle Release of oocyte Transudation of plasma into follicle Swallowing of follicle Reproduction, Marie Nováková 46 HUMOURAL REGULATION OF THE CYCLE GnRH GnRH GnRH FSH LH FSH LH FSH LH Follicular phase Ovulation Luteal phase P FSH-rec. LH-rec. P P P A E A E A E A E 90´ 360´ GnRH FSH LH 30´ Artesia of follicle (but one!) Feedback -/+/- Involution of corpus luteum Reproduction, Marie Nováková 47 EFFECTS OF OVARIAN HORMONES E P Secondary sexual signs + Adipose tissue: store (predilection), (critical amount) Bone tissue: absorption closure of fissures development of pelvis Total water retention: + + Sexual behaviour: + Ovaries: maturation of follicles Hysterosalpinx: motility motility Uterus: proteosynthesis proteosynthesis vascularisation and proliferation of endom. secretion of endom. glands EXCITATION glycogen RELAXATION Cervix: colliquation of „plug“ creation of „plug“ Vagina: cornification of epithelium proliferation of epithelium Mamma: growth of terminals growth of acines Reproduction, Marie Nováková 48 PREGNANCY, PARTURITION, LACTATION Reproduction, Marie Nováková 49 FERTILISATION PROCESSES COAGULATION OF SPERM LYSIS 20´ CAPACITATION 1 – 3 hours vagina pH viability of sp. 1-3 days hysterosalpinx cervix uteri prostaglandines hyaluronidase Spermatozoa: 108 103 10 motility of sp. 3 mm/min fertilization 1 1. Chemoattraction 2. Fixing of spermia on zona pellucida 3. Penetration and acrosomal reaction (acrosin) 4. Fusion (fertilin, membr. potential change) Syncytiotrophoblast, cytotrophoblast; decidua; implantation Immune changes in pregnancy (polymorfic MHC genes of class I., II. vs. non-polymorfic HLA-G). Reproduction, Marie Nováková 50 Ganong´s Review of Medicial Physiology Reproduction, Marie Nováková 51 HORMONAL PROFILE DURING PREGNANCY I. II. III. trimester hCG P E PROL Relaxin hCS OX 0 10 20 30 40 weeks of pregnancy STH TSH ACTH INS KORT ALD T4 PTH Placental – maternal – foetal source of hormones Corpus luteum graviditatis hCG, hCS, E, PE, P, Relaxin (8th week!!!) luteinisation and luteotropic effects inhibition of myometrial contractions preparation of lactation growth hormone in pregnancy induction of parturition Placenta Reproduction, Marie Nováková 52 RELATIONSHIP BETWEEN P:E IN PREGNANCY P E P > E E > P MOTHER PLACENTA FOETUS cholesterol pregnenolone DHEAS 16OH-DHEAS progesterone cortisol aldosterone DHEAS estradiol Estriol Foetal-placental unit Excretion of estriol in urine – index of foetal status Reproduction, Marie Nováková 53 Peptide Hormones and Neuropeptides hCG Thyrotropin (thyroid-stimulating hormone [TSH]) Placental-variant growth hormone hCS1 and hCS2, also known as hPL (hPL1 and hPL2) Placental proteins PP12 and PP14 TRH Corticotropin-releasing hormone (CRH) Growth hormone–releasing hormone (GHRH) GnRH Substance P Neurotensin Somatostatin Neuropeptide Y ACTH-related peptide The inhibins Steroid Hormones Progesterone Estrone Oestradiol Estriol Reproduction, Marie Nováková HORMONES PRODUCED BY PLACENTA 54 PHYSIOLOGICAL CHANGES DURING PREGNANCY Changes of reproduction organs • Uterus – Growth (from 60 g to 1000 g), change of position – Hyperaemia – Functional differentiation of myometrium • Cervix – Changes of colour, consistency; shortening – Hypertrophy a hyperplasia of glandules – mucus plug • Vagina – Changes of colour, increase of secretion • External genitals – Vascularization, vasocongestion (changes of colour) Somatic changes • Breasts – Growth – alveolar as well as ductal part – Enlargement and hyperpigmentation of mammillae and areolas • Skin – Increase in subcutaneous fat – Changes in connective tissue – Hyperpigmentation Endocrine and metabolic changes Immunological changes Psychic changes Reproduction, Marie Nováková 55 ENDOCRINE and METABOLIC CHANGES DURING PREGNANCY Endocrine glands • Thyroid gland – Slight hypertrophy (E), increase in thyroxine production, in III. trimester BEE +25% • Parathyroid glands – Increase in production of parathormone • Adrenal glands – Increase in production of aldosterone • Pancreas – Hyperplasia of Langerhans islets Anterior pituitary gland Metabolism • Weight gain: 12-15 kg • Glycaemia – Glc – main energetic source for foetus – Prohyperglycemic state – Decrease of renal glucose reabsorption, increase in glomerular filtration - glycosuria – Gestational diabetes • Increased demand for Ca (1300 mg), P (1200 g) and Fe (18 mg/day) • Water retention: + 6.5 l Reproduction, Marie Nováková 56 OXYTOCIN - Mechanoreceptors/tactile receptors - Magnocellular neurons (PVN, SON) - inhibition by endogenous opioids, NO, GABA - Autocrine (+ ZV) - Prolactin, relaxin (-), Estrogens (+) - OXT receptors (Gq/11) – effect of up/down regulation - Acts together with prolactin and sex hormones Functions - Lactation (under 1 min) – MILK EJECTION - Parturition - rhythmical contractions of smooth muscles (gap-junction, stimulation of prostaglandin synthesis – extracellular matrix) - postpartum bleeding - uterus involution - Ejaculation (males) - Behavior Other functions and places of synthesis - CNS - Stimulation of ACTH secretion through CRH - Stimulation of ADH/induced vasoconstriction - Stimulation of prolactin secretion - Memory traces recollection inhibition - Maternal behavior Reproduction, Marie Nováková 57 OXYTOCIN RECEPTORS - OXT receptors (Gq/11) - Myoepithelial cells - Myometrium - Endometrium - CNS - PLC, IP3, Ca2+ - Target molecule – MLCK (myosin light chain kinase) Reproduction, Marie Nováková 58 – 9 AA, differs from ADH in the 3. and the 8. AA – Precursor molecule is synthetized in the same location as ADH (nucleus paraventricularis) – Stimulus for synthesis: dilatation of birth path caused by pressure of foetus and stimulation of mechanoreceptors at breast nipple – Reflex release: during breast-feeding, orgasm – Main effects – on reproduction system: • Uterokinetic effects (induction of parturition), milk ejection, involution of uterus • In men: probably increases contractions of smooth muscle in ductus deferens – Regulation of water and mineral metabolism – natriuretic effect, potentiation of ADH effect – Effect on memory: opposite to ADH effect – inhibits forming of memory and its recollection – Note: Melanocytes inhibiting factor – from oxytocin, modulates certain types of receptors, modulation of melatonin effects (melatonin – epiphysis, together with glomerulotrophin and DMT, circadian/circannual biorhythms, controlled by hypothalamus, information from retina) OXYTOCIN Reproduction, Marie Nováková 59 INDUCTION OF PARTURITION P > E E > P maternal placental foetal CHOLESTEROL HT ACTH OXYTOCIN DHEA PREGNENOLONE CRH EP CORTISOL PG oxyt.rec. conexin gap-junctions collagenase afferentation from mechanoreceptors 100x Foetal respiratory insufficiency Reproduction, Marie Nováková 60 Ganong´s Review of Medicial PhysiologyReproduction, Marie Nováková 61 LACTATION GnRH PIF PSF OX. GH FSH LH PROL. GCPH UTERUS involution MAMMA E HCSP ejection milk production stop of cycle Composition of milk: water (88%), fat (3,5%), lactose (7%), proteins (1%) trace minerals (Ca), vitamins, antibodies (hyperprolactinaemia) placental hormones 0.6-2 l/day 1 – 3 days after birth; initiated by decrease of oestrogens´ concentrations post partum Reproduction, Marie Nováková 62 LEPTIN AND REPRODUCTIVE FUNCTIONS LEPTIN IN PREGNANCY Synthesised by placenta from the 18th week of pregnancy. Dramatic increase in maternal blood after the 34th week. Synthesis in placenta, foetal adipose tissue and growing maternal adipose tissue. BUT leptin plasmatic levels in non-pregnant women do not correspond to adipose tissue amount (BMI). Decrease after delivery down to the levels typical for non-pregnant women. Leptin may play a role in proliferation and function of trophoblast, and thus affects foetal growth. LEPTIN IN NEWBORNS Plasmatic levels of leptin correspond to newborn body mass and BMI. Blood of newborn contains maternal and foetal leptin. Girls have higher levels of leptin than boys. It is supposed, that sex differentiation of plasmatic levels of leptin is already genetically given, since it is not affected postnatally by sex hormones. Reproduction, Marie Nováková