Reproductive Physiology Lyndsay Creswell Jack Thompson Learning Outcomes ● ● ● ● ● ● ● Relevant female anatomy Relevant male anatomy Female reproductive physiology Male reproductive physiology Physiology of fertilisation Physiology of labour Physiology of newborn Female Internal Anatomy Female internal anatomy Uterus: fibromuscular organ divided into 3 layers, the endometrium, myometrium and serosa. Supplied by uterine artery (internal iliac artery branch). Inferiorly it is continuous with the cervix. Communicates with fallopian tubes at each cornu Endometrium: complex mucous membrane which undergoes cyclical changes in structure and function in response to ovarian hormonal stimulation. In the first 14 days the endometrium proliferates; glands thicken and elongate under oestrogen influence (proliferative phase). In days 14-28, under the influence of progesterone, the glands swell and blood supply increases (secretor Myometrium: smooth muscle layer, relevant to menstruation and labourCervix: dense fibrous connective tissue, continuous with the uterus at internal os. The cervical canal opens into the vagina at external os Fallopian Tubes: 2 tubes which can be divided into: isthmus, ampulla and infundibulum(with fimbriae) Ovaries: supplied by ovarian artery (abdominal aorta branch). Outer cortex covered by germinal epithelium, contains follicles and theca cells. Inner medulla contains bv and CT Oogenesis (Simply: diploid cell -> haploid cell) The development of mature ova (haploid) from their primitive precursors: oogonia (diploid) Oogonia divide by mitosis during fetal life to produce primary oocytes: approx 1-2 x 10^6, which are present at birth. This is the only source of the mature ova (22 autosomes and 1 sex chromosome) which begin to develop from puberty, in contrast with the continuous replication of spermatogonia in post pubertal males. Thus, the so called ‘biological clock’, particularly as genetic abnormalities accumulate in older primary occytes (due to genetic ‘mistakes’ during meiosis) Primary oocytes begin the first meiotic division before birth. All further development arrests until puberty, when the first meiotic dision is completed. This produces a cytoplasm and nutrient rich secondary oocyte (haploid, with 2 copies of each unpaired chromosome) and a small polar body of chromosomal material. Formation of the secondary oocyte is delayed until just prior to ovulation, (stimulated by LH surge) and the secondary oocyte only completes its second meiotic division if it is fertilised. Hypothalamus-pituitary-ovarian axis Hypothalamus located at base of the brain: acts as central processing unit of the reproductive system: neuronal stimuli from the cerebral cortex are converted by the hypothalmus into pulses of gonadotrophin releasing hormone (GnRH). At the end of the menstrual cycle, oestrogen levels are low, stimulating GnRH release. The pituitary gland’s anterior lobe secretes luteinising hormone (LH) and follicle stimulating hormone (FSH) which are also known as GONADOTROPHINS. They are released under the influence of GnRH. FSH stimulates follicular development by activating granulosa cell division and secretion of oestrogen. The increasing amount of oestrogen produced by the developing follicles act to reduce GnRH and gonadotrophin levels by negative feedback; such that only one follicle, the dominant or graafian follicle can ovulate. LH has 3 known functions: 1. It stimulates theca cells, and thus the secretion of androgens, which act as precursors for the synthesis of oestrogens. 2. LH also triggers ovulation of the dominant follicle. This is known as the ‘LH surge’, when suddenly, increasing oestrogen levels trigger a positive feedback mechanism, causing a surge in LH and FSH, and thus ovulation. 3. Additionally, LH stimulates luteinisation of the follicular remnants to form the corpus luteum, which secretes oestrogen and progesterone to support the endometrium, and the potential developing embryo. Oestrogen and Progesterone Oestrogen Progesterone Secondary sexual characteristics -thelarche (breast development) -adrenarche (axillary and pubic hair development) Menstrual cycle: induces formation of secretory endometrium during which the glands become saw toothed and tortuous, producing glycogen suitable for implantation Menstrual cycle: development of mature dominant follicle and ovulation, and preparation of proliferative endometrium Induces lobuloalveolar maturation of the breasts in conjunction with prolactin during pregnancy to allow for milk production and lactation Bone protection Promotes conditions in utero suitable for pregnancy Duct growth of breasts in pregnancy Thickens cervical mucus Promotes conditions in utero suitable for pregnancy Menstrual Cycle Menstrual Cycle Days 1-4: Menstruation. The endometrium is shed as hormonal support is withdrawn. Myometrial contraction, which can be painful also occurs to expel the endometrial lining. Days 5-13: Proliferative Phase. -Oestrogen and progesterone concentration falls -Pulses of GnRH from hypothalamus increase, stimulating release of FSH and LH inducing follicular growth -Oestrogen and progesterone levels rise, thus suppressing the gonadotrophins by negative feedback such that only one dominant follicle matures from a number of primordial follicles. -However, as oestrogen continues to rise, a switch to a positive feedback loop on the hypothalamus and pituitary causes an LH surge, stimulating ovulation. The high oestrogen causes the endometrium to become proliferative, and the glands to proliferate. Days 14-28: secretory/luteal phase -Formation of the corpus luteum : the granulosa and theca cells of the ovary become swollen by fat droplets, and the structure becomes more vascular. -The corpus luteum secretes oestrogen, but significantly more progesterone. This induces secretory changes in the endometrium, to support an implanted embryo. If the oocyte is not fertilised, the lack of placental b-hcg to support the corpus luteum causes it to fail, and hormonal withdrawal. The endometrium thus breaks down in menstruation, and the cycle starts again. Functional anatomy- Male ● Testes ○ ○ ● Seminal vesicle ○ ● Contributes to 30% of semen production and creates alkalinity of semen Epididymis ○ ● Contributes to 70% of semen production and importantly provides fructose Prostate gland ○ ● Exo and endocrine function Production of testosterone and spermatogenesis Storage and maturation of spermatozoa Vas deferens ○ Causes propulsive force of spermatozoa into the ejaculatory duct where it mixes with semen before ejaculation Spermatogenesis ● Spermatogenesis occurs in the seminiferous tubules which are found in the testes. ● Spermatids are deposited in the lumen of the seminiferous tubules to undergo maturation into spermatozoa ● The most mature cells are then stored in the epididymis Spermatogenesis 2n ● Spermatogonia o o o 2n - 46 Chromosomes Produced from stem cell Undergoes mitotic division 4n 4n ● 1o Spermatocytes o o 2n 4n - 46 Paired Ch Undergoes meiotic division 2n ● 2o Spermatocytes o o 2n - 23 Paired Ch Undergoes further meiotic division n n n n ● Spermatids o o n - 23 Unpaired Ch Undergoes maturation known as spermiogenesis ● Spermatozoa o o n - 23 Ch Further maturation (addition of mitochondria and flagellation Fertilisation -Following ovulation the ovum is propelled by the movement of the cilia lining the fimbriae and fallopian tube. -Spermatozoa must penetrate the mucus of the vagina to fertilise the ovum; this occurs at ovulation when the ratio of oestrogen to progesterone is at its peak, and the mucus is thinner and less dense -The uterus contracts to aid spermatozoa motility to the fallopian tubes -The fallopian tubes contract by retrograde peristalsis to increase chances of fertilisation -300 X 10^6 spermatozoa per ejaculate -fertilising ability of the sperm is enhanced following several hours exposure to the female reproductive tract: this process is ‘capacitation’ -Fertilisation requires the sperm to penetrate the corona radiata and zona pellucida which surround the ovum. This is aided by 1) sperm motility to force their way between granulosa cells of corona radiata 2) digestive acrosomal enzymes When the first spermatozoa contacts the plasma membrane of the secondary oocyte, the zona pellucida changes chemically, becomig impermeable to other sperm. This completes the 2nd meiotic division, and a diploid zygote is formed. - Implantation -Once the diploid embryo is formed, mitotic division begins, forming a solid ball of cells, the ‘morula’ at days 3-4 -The morula is transported towards the uterus by peristalsis and action of the cilia within the fallopian tube. It reaches the uterus by day 3-4 -Day6-8, the blastocyst is formed, consisting of: 1. An outer shell of trophoblasts (fetal part of placenta) 2. Fluid filled blastocoele which forms the yolk sac 3. Inner cell mass (from which all embryonic structures develop In the first 7-10 days the morula, and then blastocyst is nourished by the secretory endometrium. Further development requires implantation of the blastocyst by the trophoblast layer. The trophoblast layer adheres to the endometrial surface, then digests it, extending like ‘finger like processes’ into the cavities formed by digestion. The endometrium becomes more vascular by the release of prostaglandins, enhancing the nutrient content, and importantly, forming the decidua.. - the blastocyst is fully buried within the decidual endometrium by days 10-12 Placenta -nutrient and gas exchange -removal of fetal waste products by diffusion into maternal blood -partial protection from teratogens and infectious agents in maternal circulation -endocrine function, including secreting oestrogen and progesterone NB soon after implantation, the chorion of the developing placenta secretes b-hcg (human chorionic gonadotropin), which acts on the corpus luteum to prevent its regression. Thus oestrogen and progesterone production from the CL continues until the placenta becomes the chief source of sex hormones from approx 3 months into the pregnancy Placental Development -After the first few weeks, the nutritional needs of the embryo cannot be met by cannibalisation of the maternal tissue. -The placenta must develop to sustain the developing foetus -A membrane derived from the trophoblasts (fetal component), the chorion, erodes the maternal capillaries of the decidua. More blood filled spaces develop, into which the chorion’s finger like processes will project. eventually forming placental villi. -Fetal blood from umbilical arteries (deoxygenated) is circulated through the chorionic capillaries within these villi (site of fetal-maternal exchnage) and is then recirculated by the umbilical vein (oxygenated). -By week 5, the placenta is well established with both fetal (chorionic) and maternal (decidual) components -The maternal and fetal blood are separated by chorionic tissue and capillary endothelium. this provides a protective barrier and allows necessary exchange. Labour ● Should normally occur at 40 weeks of gestation ● It is split into 3 stages: o 1st stage - Onset of contractions until full cervical dilatation o 2nd stage - Full cervical dilatation to birth of child o 3rd stage - Delivery of placenta Labour ● 1st stage (3-24 hrs) o Dilatation of the cervix up to 10cm o This occurs as the baby’s head descends and causes release of oxytocin from the posterior pituitary o Oxytocin driven with positive feedback loop causes contraction that increase with time o Prostaglandins also cause uterine contraction o Relaxin softens connective tissue to ease passage of baby ● 2nd stage (30-120 mins) o Delivery of baby through vaginal tract with the aid of abdominal and cervical muscle contraction o No longer than 2 hours in nulliparous and 1 hour in multiparous ● 3rd stage (15-30 mins) o Delivery of placenta o Essential that entirety of placenta is evacuated o Followed by uterine contraction and Oxytocin Myometrial contraction Cervical stretch Spinal afferents Hypothalamus Post. pituitary Lactation ● Breast development throughout pregnancy o Oestrogen - Stimulates duct growth o Progesterone - Promotes lobule growth o Prolactin & Human Chorionic Somatomammotropin - Stimulate the synthesis of enzymes necessary for milk production ● After pregnancy: o Drop in steroid levels o Suckling reflex stimulates milk production due to release of prolactin from ant. pituitary o Release of oxytocin from post. pituitary stimulates myoepithelial cell contraction leading to milk ejection from the ducts o Prolactin release also has a contraceptive role Newborn cardiac changes ● Fetal shunts: o Ductus Venosus o Foramen Ovales o Ductus Arteriosus ● Changes at birth o ↓Placental circulation→ ↑TPR→ ↑Aorta→ ↑LV→ ↑LA o Pulm expansion→ ↑Pulm oxygenation→Pulm v.dilat→ ↓Pulm resistance→ ↓Pulm Trunk→ ↓RV→ ↓RA o R→L shunt moves to L→R and closes foramen ovales o Closure of Ductus Arteriosus happens within 1-8 days o Closure of Ductus Venosus happens within 1-3 hours
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