Reproductive Endocrinology II PDF

Human reproduction, pregnancy and parturition  Intended learning outcomes Human reproduction, pregnancy and parturition Overview: Fertilisation, embryonic development and implantation. Pregnancy, parturition and lactation and their endocrine control. After the lecture and personal stud...

Human reproduction, pregnancy and parturition  Intended learning outcomes Human reproduction, pregnancy and parturition Overview: Fertilisation, embryonic development and implantation. Pregnancy, parturition and lactation and their endocrine control. After the lecture and personal study, students should be able to: Explain the physiology of the sexual response in the male and female In simple terms, explain the implantation of fertilised cells into the uterus Understand the development of placenta at the onset of pregnancy Know the changes of endocrinology in pregnancy Describe the physiology of major maternal adaptations and understand how these changes might be beneficial during pregnancy or birth Describe the endocrinology involved in the maintenance of gestation Understand the major events occurring at each of the phases of parturition Understand events which lead to lactation Understand the endocrinology of the suckling response and explain how weaning results in cessation of lactation Sexual Arousal and Ejaculation  Sexual arousal 4 stages: Excitement Psychogenic and/or somatogenic Individualized – personality and culture Plateau Orgasm Resolution  Excitement Male Female Heightened sexual awareness Heightened sexual awareness Testicular vasocongestion Vasodilation of vagina & external Engorgement of penis è erection genitalia è swelling of labia Erection of clitoris Lubrication of vagina Enlargement of breasts Flush to skin Fig. 20-13, p. 761  Plateau Male Female Intensification of excitement As male. Also ↑ HR, BP, resp rate, muscle Vasodilation of lower 1/3 of vagina tension causes tightening around penis “Tenting effect” – Uterus raises Lifts cervix Enlarges upper ½ of vagina (makes room for ejaculate)  Orgasm Male Female Intense physical pleasure Intense physical pleasure Ejaculation Rhythmic contractions of pelvic Rhythmic contractions of pelvic muscles every 0.8 secs, espec in muscles every 0.8 secs lower 1/3 of vagina (“orgasmic platform”) ↑ HR, BP, resp rate, muscle tension ↑ HR, BP, resp rate, muscle tension No ejaculation No refractory period \ can have another orgasm immediately  Ejaculation Motor neurone induced Stimulation of mechanoreceptors rhythmic contraction (0.8 / sec) in glans of penis of skeletal muscle at base of penis Sympathetic response Semen forced out thro’ urethra Contraction of smooth muscle in Prostate è prostatic fluid EXPULSION semen Reproductive ducts è sperm Seminal vesicles è s.v. fluid Number of sperm per ejaculate Secreted into (per 2.75 mL) approx 180 prostatic urethra million (66 million / mL) > 20 million / mL – clinically EMISSION infertile Table 20-4, p. 759  Resolution Male Female Temporal refractory No refractory period period – men can’t have orgasms in quick succession Relaxation Relaxation Return of body to pre excitement state Slowing of blood flow to Return of body to pre excitement state penis Implantation and Pregnancy Fig. 20-23, p. 778  Capacitation v Freshly ejaculated sperm are incapable of fertilisation v They must undergo capacitation (in the female repro tract) surface of sperm altered by removal of glycoprotein coat tail movements become whip like cAMP levels rise to promote acrosomal reaction Fig. 20-25, p. 780  Penetration of the egg by the sperm v Allurin released by mature ovum to attract sperm. Sperm “smell” this chemical using an olfactory receptor (hOR17-4). Detection tail movements and swimming in direction of the signal v Fertilin (protein on sperm) binds to integrin (adhesion molecule on 2ºoocyte) v Acrosomal reaction Enzymes in the acrosomal tip allow a sperm to “burrow” through the outer layers of ovum & enter cytoplasm “Block to polyspermy” membrane changes triggered Tail of sperm probably lost v Final meitoic division of 2º oocyte triggered – 2nd polar body formed & extruded v Sperm & egg nuclei fuse (>1hr) èzygote  Fimbriae - Sweep ovum into oviduct, carried along by smooth muscle contraction & cilia Fig. 20-26, p. 781 Fig. 20-27a, p. 782 Fig. 20-27b, p. 782 Fig. 20-27c, p. 782  Implantation 1 1. initial contact with epithelium of uterus – blastocyst sticky Endometrium uterine lining Inner cell mass Capillary 2. proteases released from trophoblast Blastocoel 3.pathways created Trophoblast allowing trophoblast cells to grow into endometrium 4. trophoblast releases nutrients for embryo  Implantation 2 Trophoblast cells tunnel into the endometrial lining Boundaries between trophoblast cells disintegrate – “syncytiotrophoblast” will become foetal placenta Trophoblast induces “decidualization” of endometrium – increased local vascularization and nutrient storage Blastocyst becomes buried in uterine lining by day 12  Development of Placenta § Placenta derived from both trophoblast & decidual tissue § Trophoblast cells (chorion) differentiate into multinucleate “syncytiotrophoblasts” which invade decidua and break down capillaries to form cavities filled with maternal blood § Developing embryo sends capillaries into the syncytiotrophoblast projections to form “placental villi” § Each villus contains foetal capillaries separated from maternal blood by a thin layer of tissue – no direct contact between foetal & maternal blood § 2 way exchange of respiratory gases, nutrients, metabolites etc between mother and foetus, largely down diffusion gradient Placenta and foetus Umbilical cord Pool of maternal blood Amniotic sac Placental villus Uterine decidual tissue Maternal arteriole Maternal venule Fetal vessels Chorion Chorionic tissue Umbilical Umbilical Placenta vein artery Hormonal maintenance of pregnancy – 1st trimester What stops the implanted foetus being swept away with the menstrual lining during menstruation? Human chorionic gonadotropin (hCG) Produced by the blastocyst Prolongs life of corpus luteum (now called c.l. of pregnancy) For 10 further weeks, C.l. of pregnancy grows and produces increasing concs of progesterone & oestrogen (1st trimester) After 10 weeks, the placenta produces these hormones \ uterine lining is maintained during pregnancy Pregnancy test – hCG detected in urine throughout pregnancy Morning sickness – hCG may trigger vomiting centre At end of 1st trimester, hCG stimulates male foetal gonads to produce steroid hormones è genitalia differentiation  Hormonal maintenance of pregnancy hCG secreted by Human chorionic gonadotropin (hCG) chorion to oestr. & prog. maintain levels rise as pregnancy placenta grows Oestrogen hCG sustains Progesterone corpus luteum – oestrogen & progesterone Corpus secreted to maintain luteum pregnancy regresses- no longer needed for steroid output Fertilization Delivery  Why doesn’t oestrogen initially come from the placenta? Why doesn’t the placenta secrete oestrogen in the first place? - placenta does not possess all the enzymes needed for oestrogen synthesis in the 1st trimester Placenta requires dehydroepiandosterone (DHEA) from foetal adrenal cortex, which takes time to develop “foetoplacental unit” is used: Maternal Blood Placenta Foetal blood Foetal adrenal cortex cholesterol cholesterol progesterone progesterone DHEA DHEA Oestrogen (Oestriol) oestrogen Placenta CAN synthesise progesterone, but small amounts at first  The roles of oestrogens and progesterone in pregnancy Secreted by the corpus luteum of preg in 1st trimester and placenta in 2nd and 3rd trimesters Oestrogens Stimulate growth of myometrium musculature – to expel foetus during labour Stimulate development of mammary gland ducts Progesterone Suppresses contractions of uterine myometrium Promotes formation of mucus plug Stimulates development of mammary milk glands  Gestation Human gestation approx 38 weeks from conception, approx 40 weeks from last period Embryo / foetus grows and develops § Mother undergoes physical changes: § Enlargement of uterus (and placenta) § Enlargement of breasts which become able to produce milk § ↑ blood vol (oestrogen stimulates angiotensinogen & renin secretion. Aldosterone retains Na+ and water) § Weight gain § ↑ pulmonary ventilation & Vo2 § ↑ GFR è ↑ urine § ↑ nutritional requirements for the mother  Endocrine secretions of the placenta during gestation hCG oestrogens and progesterone Other placental hormones? Human chorionic somatomammotropin (hCS): ↓ maternal glucose utilization, ↑ plasma FA - ↑ glucose and FA availability for foetus ? prepares breast glands for lactation ? Parathyroid hormone – related peptide (PTHrp): Mobilises maternal Ca2+ for calcification of foetal bones (if mother’s diet does not contain enough Ca2+) Relaxin : softens cervix, loosens pelvic connective tissue Placental Corticotropin Releasing Hormone (CRH): stimulates DHEA production by foetal adrenal cortex – important in initiation of parturition Table 20-5, p. 787 Parturition and Lactation  Parturition Labour, delivery or birth Requires § Dilation of the cervical canal § To allow passage of the foetus § Contractions of uterine myometrium § To cause expulsion of the foetus Preparation for parturition Braxton-Hicks contractions § “false labour” – increased uterine sensitivity Softening of cervix § Caused by relaxin & prostaglandins § Breakdown of cervical collagen fibres allows cervix to dilate during labour Relaxation of pelvic bones § Caused by relaxin Foetus “drops” § Head is in contact with cervix § cf. a breech birth  In proportion to size of placenta? What (into fetal circulation) appears to initiate labour? CRH = corticotropin releasing hormone Increased oestrogen synthesis by placenta produces dose- dependent changes in uterus §oestrogen increases density of oxytocin receptors in myometrium § maternal [oxytocin]p does not rise – parturition triggered by raised oxytocin sensitivity of myometrium § oxytocin acts via IP3 - raises cytoplasmic [Ca++ ] Uterine contractions Push fetus Positive against cervix feedback facilitates progression of parturition (through neuroendocrine reflex) Oxytocin Prostaglandin secretion production  1st stage of labour Cervical dilation stage May take many hours Rupture of amniotic sac - “waters break” Lubricates birth canal Cervix dilates to 10cm to accommodate the baby’s head Breech birth – another part of body approaches cervix first Cervix partially dilated  2nd stage of labour Delivery of the baby Usually takes 30-90 minutes Baby moves thro’ cervix to vagina Stretch receptors in vagina trigger contraction of abdominal wall to augment uterine contractions Mother can voluntarily contract abs also (“push”) After birth, the baby is freed from placenta by cutting umbilical cord Cord is tied and forms umbilicus  3rd stage of labour Delivery of the placenta placenta Takes 15-30 minutes Placenta separates from myometrium and uterine contractions cause it to be expelled – “afterbirth” Myometrium contracts and prevents haemorrhage by constricting uterine blood vessels Umbilical cord at site of placental attachment Involution Shrinkage of uterus to pre-pregnancy size Takes 4-6 weeks Induced by Fall in oestrogens and progesterone levels after placenta is lost Oxytocin which is released in response to breast feeding LOCHIA Development of the breast In non- pregnant state, mostly adipose adipose and rudimentary ducts tissue ducts Breast doesn’t fully develop until nipple pregnancy Development of glandular structure lobules Each duct terminates in a lobule myoepithelial Lobule made of milk cells producing glands – alveoli Milk secreted from epithelial cells into lumen milk  What triggers development of the breast? During pregnancy, ↑ oestrogen è duct development ↑ progesterone è lobule formation Prolactin (ant pit hormone) & human chorionic somatomammotropin (placental hormone) è Synthesis of enzymes for milk production Breasts are mature by month 4 of gestation Prolactin also stimulates milk production after parturition Stimulatory action of prolactin is blocked in later stages of pregnancy by high levels of oestrogen and progesterone Immediately after parturition oest & prog levels fall, allowing prolactin to induce milk production  Suckling Suckling triggers Neuroendocrine reflex - leads to secretion of Prolactin è milk production Oxytocin è milk ejection (a.k.a. LETDOWN) Oxytocin stimulates contraction of myoepithelial cells Oxytocin hastens involution Oxytocin suppresses LH & FSH secretion – suppresses menstrual cycle  Suckling Mechanoreceptors in nipple Hypothalamus Nervous Prolactin-inhibiting hormone (PIH) or pathway prolactin-releasing hormone (PRH)(?) Posterior pituitary Anterior pituitary Oxytocin Prolactin Contraction of myoepithelial cells surrounding alveoli Milk secretion Milk ejection  Components of breast milk More than 100 constituents Delivers about 600-750 Kcal/L Emulsion of particles isotonic with plasma Water Lactose about 7% but lower in colostrum Lipids 3-5% Vitamins Minerals e.g., calcium, phosphate, sodium, Mg, Cl- etc Immunoprotective agents – various – especially plentiful in colostrum Other proteins (including immunoglobulins) - Highest conc of protein in colostrum Colostrum = milk produced in first 5 days after birth Cessation of breast milk production No suckling After weaning No prolactin No oxytocin No milk ejection No milk production Milk accumulates in alveoli Pressure build up acts directly on alveolar epithelial cells