Reproductive Systems.docx

Female Reproductive Anatomy Uterus (the womb)- A thick muscular organ lined by the endometrium which is rich in blood vessels Vagina (the birth canal)- Receives sperm during copulation Cervical canal (cervix)- Neck of the uterus (opens into the vagina) External features of female reproductive anatom...

Female Reproductive Anatomy Uterus (the womb)- A thick muscular organ lined by the endometrium which is rich in blood vessels Vagina (the birth canal)- Receives sperm during copulation Cervical canal (cervix)- Neck of the uterus (opens into the vagina) External features of female reproductive anatomy: labia and vaginal opening Cilia convey the egg towards the uterus The Oviduct -The opening of the Fallopian Tube -Ciliated funnel-like -‘Collects’ the egg by drawing in fluid The ovaries contain follicles (The basic functional units)Ovum + layers of cells (to protect and nourish the egg) A female has up to 500,000 follicles • Formed before birth • Primary source of oestrogens Ovaries • Attached to the uterus by mesentery • Enclosed by a protective capsule • Releases egg into the abdominal cavity Oogenesis Development of ova (mature unfertilized egg cells) Oogonia = stem cells in embryo (form ova) Oogonia multiply and undergo meiosis This stops at prophase I (Primary oocytes) These remain ‘arrested’ in follicles until puberty FSH stimulates follicle growth ↓ Completion of meiosis I and the start of meiosis II Arrested at metaphase II (Secondary oocyte) What happens when an egg is penetrated by a sperm? Completion of 2nd meiotic division triggered Fertilized egg (oogenesis complete) Regulation of female reproduction is a cyclic process unlike male reproductive physiology. One ovum released per cycle, regulation is complex and requires hormones. Hormonal regulation of reproduction in females Synchronization between follicle growth, ovulation and endometrial thickening (in preparation for possible pregnancy In hypothalamus, gonadotropin-releasing hormone is released (GnRH) In anterior pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is released In ovaries, oestrogen (oestradiol) and progesterone are released Ovarian cycle Day 1-13 is follicular phase Day 14 is ovulation Day 15-28 is luteal phase Menstrual cycle Day 1-4 is menses Day 5-14 is proliferative phase Day 15-28 is secretory phase Follicular phase Several follicles begin to grow Only one continues to develop, others disintegrate! OESTROGEN dominant Ovulation Release of the secondary oocyte Luteal phase Follicular tissue remaining in the ovary develops into the corpus luteum PROGESTERONE dominant The ovary contains follicles at many different stages of development as follicle development can take months. Menstrual flow phase 3 – 7 days Loss of the functional endometrial layer Proliferative phase 1 or 2 weeks Regeneration of the endometrium Secretory phase 2 weeks Vascularization and glandular development of the endometrium Menstrual flow phase Shedding of the previous endometrium and the corpus luteum-Hormone secreting cells in the ovary (following ovulation) Menstrual Disorders & Infertility Amenorrhea-The absence of menstruation Primary Amenorrhea- Never had a period (age 15+) Secondary Amenorrhea- >3 consecutive missed periods (previously menstruated) Normal physiological causes of secondary amenorrhea are: • Pregnancy • Menopause • Breastfeeding Oligomenorrhea- Infrequent + inconsistent menstruation. Oligomenorrhea occurs during early menstruation, postpartum or perimenopausal women Also a common feature of PCOS Causes of primary amenorrhea -Genetic abnormalities such as androgen insensitivity syndrome (high testosterone) -Anatomical problems such as uterine scarring, abnormal endometrium shedding, blocked reproductive tract or missing or abnormal development of reproductive organs -Hormone imbalance caused by impaired hypothalamus or pituitary gland function (common) Hypothalamic amenorrhea can be seen in underweight women that are <10% below normal weight or athletes that undergo strenuous activity and restricted diet. This is due to low fat reserves in their body which means less adipose tissue, this causes less leptin secretion which decreases the release of GnRH hormone which causes no/delayed ovulation and menstruation. Polycystic Ovary Syndrome (PCOS) Affects approximately 6% of pre-menopausal women. PCOS includes abnormal hormone levels. High androgen causes enhanced, dysfunctional follicular development which causes the formation of cysts and low functional ovarian reserve (infertility). PCOS also means that there is a LH and FSH imbalance which interferes with ovulation and causes oligomenorrhea in 75-85% of women that have PCOS, this leads to hyperinsulinemia which causes weight gain. What factors can impact male fertility? -Poor motility of sperm -Low concentration of sperm -Poor morphology of sperm How can we assist reproduction with low sperm concentration and motility? -Concentrating sperm and selecting the ‘best swimmers’ -Sperm obtained surgically from the testis/male reproductive tract Assisted reproductive Techniques -Intrauterine insemination (IUI) -In vitro fertilisation (IVF) -Intracytoplasmic sperm injection (ICSI) Summary of female reproductive system • Internal reproductive structures • Cyclical gamete production – with extended periods of rest • Hormonal regulation is very complex Involves the same hormones as in males • During pregnancy, short term override mechanisms ensure endometrial integrity • Dysregulated endocrine function can contribute to female infertility The roles of the male reproductive tract -Formation of gametes (sperm) -Deposition of these in the female tract (for sexual reproduction) Testis- The site for gamete production Penis -Role in the deposition of gametes in female tract Vas Deferens -Sperm moved by deferens (from the epididymis) -Terminates in the ejaculatory duct (near the prostate gland) The ejaculatory ducts open into the urethra. What makes up semen? Ejaculated Fluid = Sperm and Secretions From: Seminal vesicles Prostate gland Bulbourethral glands (Cowper’s gland) The role of the testes Testes is made up of seminiferous tubules which produces sperm and androgens (especially testosterone) and testes delivers sperm to the penis The Testes ~800 seminiferous tubules per testicle Coiled structures made up of 2 cell types:-Sertoli cells (epithelial cells) -Sperm cells (found adjacent to Sertoli cells) Leydig cells- Found between the tubules, produce testosterone Role of Sertoli cells Sertoli cells line the walls of the seminiferous tubules • Source of nutrition to sperm • Phagocytosis of dead sperm • Formation of the blood-testes barrier • Production of seminiferous tubule fluid What determines male and female development? Male and female gonads are derived from the same embryological tissue (The urogenital ridge) This remains undifferentiated until week 6. After week 6 there is a ‘double genital duct’ system which consists of mullerian ducts (Capable of developing into female reproductive organs­) and wolffian ducts (Capable of developing into male reproductive organs). Spermatogenesis Production of mature sperm (Continuous) Each ejaculate (2-10ml) contains ~100 million sperm per ml Occurs in the seminiferous tubules Sperm stem cells = Spermatogonia Spermatogonia are located at the periphery Developing sperm cells move towards the lumen as they mature Before meiotic division- Clonal expansion via mitosis First stage of meiotic division- Primary spermatocytes divide into two secondary spermatocytes Second stage of meiotic division- Secondary spermatocytes divide to form spermatids, which then differentiate into spermatozoa Testosterone Produced by Leydig cells (from acetate and cholesterol) Testosterone = An androgen Direct paracrine effect on spermatogenesis (Remainder secreted into vascular system) Most other endocrine actions are via its metabolite 5α-Dihydrotestosterone (5-α-DHT) (Due to action of 5α-reductase) Testosterone = primary sexual characteristics DHT = secondary sexual characteristics BOTH act via androgen receptors (As nuclear transcription factors) A molecule that influences the transcription of a gene or genes Control of male reproduction Gonadotropin-releasing hormone (GnRH)- Produced by parvocellular neurons (In the pre-optic area and hypothalamus). Binds specifically to receptors in the gonadotropes of the anterior pituitary gland and secretes FSH and LH. How does Viagra work? Viagra is a Phosphodiesterase (PDE) inhibitor Prevents the breakdown of cGMP Vasodilation maintained for longer Summary of the male reproductive system Male gonads require intervention during the foetal period for formation The 2 roles of the testis: -Sperm production and androgen production -Sperm production is a continuous process occurring in the seminiferous tubules Reproductive physiology is controlled by GnRH, FSH and LH Human Pregnancy Gestation (pregnancy): ~ 266 days from conception to birth Usually measured from the first day of the last menstrual period (280 days / 40 weeks) A pregnancies term = its duration Divided into 3X 3-month trimesters Fertilisation Occurs in distal half of Fallopian tube Only 0.00001 % of spermatozoa reach the egg (~ few 1000 of ~200 million) Takes 24-72 hours Egg does not live long enough to reach uterus (12-24 hours) Capacitation in sperm Sperm must first undergo capacitation (in the uterus) Increase in Membrane calcium permeability Increase in Motility Destabilizes the membrane of the acrosomal region Allows for an acrosomal reaction (When sperm encounters an egg) Enzymes released via Ca2+ influx (Acrosin and other proteases) These enable the sperm to penetrate the egg Once the sperm penetrates the egg: • Oocyte completes meiotic divisions • Must prevent polyspermy (via the cortical reaction) • Must prevent degradation of the corpus luteum (the zygote secretes human chorionic gonadotrophin) The first sperm is not necessarily the one which fertilizes the egg Stages of Pregnancy Blastocyst- During conception (2 weeks post-fertilisation) Embryo- 2-8 weeks Foetus- From 9 weeks until birth Birth Neonate- 6 weeks following birth Blastocyst Stage The pre-embryonic stage (0-2 weeks) 3 stages: 1. Cleavage 2. Implantation 3. Embryogenesis Cleavage Begins almost immediately after fertilization Mitotic divisions result in blastomeres After 72 hours, it consists of a ball of cells called the morula Hollows out to form a blastocyst Implantation ~6 days after fertilization The blastocyst attaches and embeds into endometrium The trophoblast begins to form the placenta This will ultimately nourish the foetus (11 days – 12 weeks) The trophoblast secretes Human Chorionic Gonadotropin (HCG) Stimulates corpus luteum (the chorion will eventually replace this role) to secrete Oestrogen and Progesterone (suppresses menstruation) Pregnancy tests detect Human Chorionic Gonadotropin (HCG) Embryogenesis Occurs during implantation Blastomeres form into 3 primary germ layers All body systems present after 8 or 9 weeks Beginning with CNS development (Neurulation) in 1st month Foetal development- from 9 weeks until birth the growth and differentiation of organs are formed during embryogenesis Maternal physiological adaptations in pregnancy The Cardiovascular System Decrease in Total Peripheral Resistance (in the first half of pregnancy) Affects other circulations: Increase in Glomerular Filtration Rate (Renal) For elimination of foetal waste products Increase in Cardiac Output (both stroke volume and heart rate) Increase in Blood volume and Increase in Preload Increase in Contractility (some ventricular hypertrophy) Less favourable adjustments to pregnancy Blood pressure needs to be maintained However, low resistance in the placenta so Decrease in Diastolic pressure and wider pulse pressure RBC count does not increase enough to match the increase in plasma volume (Physiological anaemia) Increase in Pressure by the uterus on pelvic blood vessels Impairs venous return means varicose veins and oedema Pre-eclampsia High blood pressure disorder during pregnancy, often with proteinuria More common in 3rd trimester Common cause is abnormal placentation Failure of trophoblast differentiation which means Inadequate invasion which means Narrow & highly resistant spiral arteries Eclampsia The onset of seizures or a coma with symptoms of preeclampsia Before, during or after delivery Difficult to predict progression to eclampsia Often no warning signs or symptom Gestational Diabetes Diagnosed for the first-time during pregnancy Effects ~16.5% of pregnancies globally Less effective use of insulin which means high blood sugar (chronic hyperglycaemia) Risk factors for gestational diabetes: Older maternal age Obesity Lack of physical activity Pre-diabetic / family history PCOS Increases the risk of: CVD and T2DM in mother and child Macrosomia Future obesity of infant Gestational diabetes disappears following birth Parturition Initiation of labour Oestrogens Promote production of PGF2α Increase in Oxytocin receptors Promotes contraction Oxytocin Activation of the Hypothalamus = further Oxytocin release Accumulation of oxytocin Increase Rate and intensity of uterine contractions Following birth – Feedback ends No further oxytocin production Uterine contraction Uterine Smooth Muscle: Increase in Calcium = Contraction Decrease in Calcium = Relaxation G-Protein Coupled Receptor signalling increases intracellular Calcium Oxytocin can modulate contraction! Complication in labours -Preterm birth (too early in pregnancy)- can be treated by oxytocin receptor antagonists -Slow to progress labours (weak contractions/uterine atony) can be treated by synthetic/exogenous oxytocin -Post-partum haemorrhage