Reproductive System PDF

Reproductive System Acknowledgement - We would like to preface these slides by saying that when we use the terms ‘man/woman/male/female’ we are typically referring to cisgendered people - We acknowledge that some of the terminology used in these slides are not inclusive of transgender, gender diverse & intersex anatomy/experiences and we would like you to actively consider this as you are reading - We encourage you to read up on these topics, you will encounter diverse patients & knowledge in these areas will be important in your future career as a doctor and for the safety of your future patients - Resources: - https://www.hrc.org/resources/transgender - https://www.wavelengthmeded.org/ - What is gender diversity Acknowledgement Some terminology to consider: When referring to ‘female’ anatomy - are you speciﬁcally referring to someone with a uterus/ovaries? Referring to people who menstruate? Not all women have a uterus (think people who’ve had hysterectomies, trans women), not all women menstruate (many women are post-menopausal), and not all people who menstruate are women (trans men, non-binary people) When referring to ‘male’ anatomy consider the same - not all people with testes identify as a man, and not all men have testes. Not all people with breasts are women - breast tissue is present in all people, and as such should not be gendered. VIDEOS - ﬁnd them on our ✨ youtube ✨ 1 - Descent of testes + spermatic cord contents 2 - Sex differentiation pathway + 5 alpha hydroxylase deﬁciency 3 - Ovarian / Uterine cycle 4 - Physiology: Early life + fertilisation, Placentation + foetal growth, Birth General anatomy Pelvic viscera Female anatomy Anatomy Male anatomy Perineal muscles Infertility Histology Sex differentiation General Anatomy Bony Structures of the Pelvis Bony Structures of the Pelvis Bony Structures of the Pelvis: LASIS) Major Ligaments of the Pelvis Sacrospinous ligament -CrOSPROsTchium ○ Sacrum → ischial spine Sacrotuberous ligament ↳ ○ Sacrum → ischial tuberosity acrotuberouserosity spine Theberosity Ligaments of the Pelvis Pelvic Inlet Posterior : Sacral pomontary Borders : of Enterior : Public Symphysis (Iliopectineal Line True vs False Pelvis Lateral : Arcuate Line Pelvic Outlet : Posterior : Coccyx Anterior : Public Arch and Lateral : Sacrotuberous ligament True pelvis (lesser pelvis) - pelvic proper cavity Ischeal tuberosity False pelvis (greater pelvis) - superiorly projecting ilia (technically in abdominal cavity) Separated by pelvic brim (pelvic inlet border) Pelvic Inlet and Pelvic Outlet pelvic inlet borders = pelvic brim posterior - sacral promontory + sacral wings (ala) lateral - arcuate line (inner surface of ileum) + pectineal line (inner surface of superior pubic ramus) anterior - pubic symphysis pelvic outlet borders posterior - tip of coccyx lateral - ischial tuberosities + sacrotuberous ligament anterior - pubic arch **linea terminalis = arcuate line + pectinate line Pelvic planes & dimensions articulates with L5 vertebrae ) - True conjugate: sacral promontory → superior border of pubic symphysis - Obstetric conjugate: narrowest ﬁxed distance that the foetus would have to pass through (the minimum AP diameter of the pelvic inlet the baby would have to pass through) - sacral promontory → midpoint of pubic symphysis - Diagonal conjugate: sacral promontory → inferior border of pubic symphysis - Transverse diameter: ischial spine → ischial spine Male vs Female Pelvis Male (android) Female (gynecoid) heart shaped, narrow oval and rounded, wider to accommodate for childbirth narrow ischiopubic rami angle (around 70 wider ischiopubic rami angle (around 90-100 degrees) degrees) circular obturator foramen oval obturator foramen higher iliac crests shorter iliac crests ischial spines more prominent, closer together ischial spines less prominent, wider apart (> 12cm) longer, narrower, straighter sacrum, more shorter, wider sacrum with less pronounced sacral pronounced sacral promontory with less posterior promontory, more curved posteriorly curve Male vs Female Pelvis Who goes through who in the pelvis? Location Contents Under the inguinal - External iliac vessels leave & become femoral ligament vessels below the ligament - Femoral n. Through the inguinal canal Females: round ligament - Males: contents of spermatic cord + vas deferens Through the greater sciatic - Superior/inferior gluteal a, v, & n. foramen - Sciatic nerve - Pudendal nerve - Internal pudendal a. & v. Through the obturator Obturator nerve & vessels canal Through the urogenital - Urethra (males + females) - hiatus - Vagina (females) knee External Iliac Artery Aeris> Femoral Artery- Popliteal Artery Under the Ext iliac vessels 1. inguinal ligament : ·. leave and turn into femoral vessels · Femoral nerve. 2 through the inguinal canal : · Round Ligament (females · Spermatic cord and was deferens (males). Greater 3 Sciatic foramen :· Sciatic nerve · Pedundal nerve (for genitals and anus).) Binf Gluteal nerves (sup - · Internal peduncal arteries and veins. 4 Obturator Canal : Obturator nerve a vessels Hiatus Urethra. 5 Urogenital : · Vagina (females) Passageways in and out of the Pelvis Pelvic Floor Muscles Levator ani = pubococcygeus + puborectalis + iliococcygeus Coccygeus (ischiococcygeus) ↳ publis to rectum ↳ publis to coccyxX ↳ ilium to coccyx bischium to coccyx Levator Ani Coccygeus (Ischiococcygeus) Puborectalis Pubococcygeus Iliococcygeus Origin Posterior surface of pubic bones Tendinous arch of internal Ischial spines obturator fascia, ischial spine Insertion Forms U shaped sling - Anococcygeal ligament, Anococcygeal ligament, Lateral aspect of sacrum posterior to rectum coccyx, perineal body and coccyx and coccyx (along musculature of sacrospinous ligament) - prostate/vagina - Innervation Nerve to levator ani (S4) & Pudendal nerve (S2-4) - Anterior rami of S4/5 Blood Supply Inferior gluteal, inferior vesical, pudendal arteries Other Stability and support of abdominal and pelvic organs Smaller and most Resistance against increased intra-abdominal pressure posterior component Opening and closing of levator hiatus (urogenital hiatus + rectal/anal hiatus) Pelvic Wall Muscles Obturator internus Piriformis Obturator Internus Piriformis * Obturator interns : - lesser sciatic foramen artery · superior gluteal Origin Pubis and ischium at obturator foramen, Anterior surface of sacrum inferior gluteal artery travels through lesser sciatic foramen Piriformis : - * Insertion Greater trochanter of femur Innervation Nerve to obturator internus Nerve to piriformis Blood Supply Superior gluteal artery Inferior gluteal artery Action Rotate thigh laterally Innervation of the pelvis The main innervation of the pelvis come from 2 nerves (these are part of the sacral plexus which is located on the posterolateral wall of the lesser pelvis): foramen : Superior gluteal nerve 1. Sciatic n. * Suprapiriformis 2. Pudendal n. foramen : EVERYTHING EISE * Infrapiriformis sciatic nerve , (Inf - gluteal nerve, Sciatic nerve (L4, L5, S1, S2, S3): pudendal.) nerve etc - Largest nerve - Passes through the greater sciatic foramen & travels inferior to the piriformis - Supplies the posterior thigh muscles + sensory innervation of most of the leg + foot Pudendal nerve (S2, S3, S4): - Exits pelvis via the greater sciatic foramen - Re-enters pelvis via the lesser sciatic foramen - Courses through the pudendal canal (Alcock’s canal), formed from the fascia of the obturator internus - Supplies motor innervation to: pelvic ﬂoor muscles, external anal + urethral sphincter - Supplies sensory innervation to perineum Other nerves of the perineum reme Superior gluteal nerve gentea - Leaves pelvis via greater sciatic foramen - Leaves superior to piriformis superimentalRAME SCIATI GREATER Inferior gluteal nerve - Leaves pelvis via greater sciatic foramen - Leaves inferior to piriformis + superﬁcial to sciatic nerve - Breaks into several smaller branches after Blood supply through the pelvis Horta Pelvic arteries Left L Iliac Common Iliac Common Right S1 > - Birfucation between LS and Ureter crosses over > - L ~ Internaliliac External (Liac Internal iliac artery ↓ Supplies pelvis - Supplies most of the blood to the pelvic viscera + musculoskeletal part of the pelvis - Also supplies branches to the gluteal region, medial thigh & peritoneum - Begins as the common iliac a. → bifurcates into the internal + external iliac aa between L5 & S1 - Ureter crosses the common iliac artery on its bifurcation - Internal iliac artery ends at the greater sciatic foramen by dividing into anterior + posterior divisions Pelvic arteries Umbilical artery - Before birth: - Umbilical arteries are the main continuations of the internal iliac aa. - Conducts oxygen + nutrient-deﬁcient blood to the placenta - When the umbilical cord is cut: - Distal parts of the umbilical arteries don’t function - Become occluded and form the medial umbilical ligaments + raise the median umbilical folds Obturator artery - Origin is variable - Is crossed by the ureter (water under the bridge!) - Passes between the obturator nerve + vein Superﬁcial perineal pouch - Potential space between perineal fascia + perineal membrane - Bound laterally by the ischiopubic rami Contents (males): - Root of penis & muscles - ischiocavernosus & bulbospongiosus - Proximal (bulbous) part of spongy urethra - Superﬁcial transverse perineal muscles - Deep perineal branches of internal pudendal vessels & nerves Contents (females): - Clitoris & muscles (ischiocavernosus) - Bulb of the vestibule & muscles (bulbospongiosus) - Greater vestibular glands - Superﬁcial transverse perineal muscles - Deep perineal branches of the internal pudendal vessels & nerves Deep perineal pouch Boundaries: Contents (male): - Inferior = perineal membrane - Intermediate urethra - Superior = inferior fascia of the pelvic - Deep transverse perineal muscles diaphragm - Bulbourethral glands - Lateral = inferior obturator fascia - Dorsal neurovascular structures of the penis Contents (both sexes): Contents (female): - Part of the urethra - Proximal urethra - External urethral sphincter - Dorsal neurovasculature of the clitoris - Is more trough-like in males - Ischioanal fossa Fascia in Urogenital Triangle S deep to superﬁcial deep perineal pouch perineal membrane superﬁcial perineal pouch perineal fascia deep fascia superﬁcial fascia superﬁcial layer - continuous with Camper’s fascia deep layer (Colles’ fascia) - continuous with Scarpa’s fascia skin Umbilical Folds / Ligaments Median umbilical fold (useless in adult) ○ Remnant of foetal urachus Medial umbilical folds (useless in adult) Lateral umbilical folds (USEFUL) ○ Contains inferior epigastric vessels - ○ Originates medial to deep inguinal ring and ends at arcuate line ***Classiﬁcation of hernias: Direct hernia - medial to lateral umbilical fold Indirect hernia - lateral to lateral umbilical fold Pelvic Viscera Viscera of the True Pelvis 1. Bladder a. Formed by the detrusor muscle b. Only section of the bladder without the detrusor muscle is the trigone (patch of smooth muscle) c. At the apex of the trigone is the ureter + internal urethral oriﬁce 2. Uterus (females only) 3. Rectum Pouches of abdominal viscera Vesico/ Vesical = Bladder Females have 2 pouches whereas males only have 1. bladder between rectum and - Rectovesical pouch (males only) - - - Most inferior part of the peritoneal cavity in males - Rectouterine pouch/pouch of Douglas (females only) - Most inferior part of the peritoneal cavity in females - Between rectum + uterus - Fluid accumulates here in the erect position - Vesicouterine pouch (females) - Between the bladder + uterus Bladder vasculature and lymphatics - Arterial supply - Superior vesical branch of the internal iliac a. - Additional supply: females - vaginal arteries & males - inferior vesical artery - Venous drainage - Vesical venous plexus which empties into the internal iliac veins - Lymphatics - Superolateral aspect: external iliac lymph nodes - Neck + fundus: internal iliac, sacral + common lymph nodes Nervous Supply of Bladder fight Sympathetic - hypogastric nerve (T12-L2) flight - or Parasympathetic - pelvic splanchnics (S2-4) 3 Autonomic - rest and digest Somatic - pudendal nerve (S2-4) - - voluntary movements Sensory afferent nerves - signal need to urinate when bladder is full Micturition Reﬂex: When controlled When controlled store urine void urine Curinate) by : by : detrusor muscle sympathetics > - relax parasympathetics contract (smooth) > - internal urethral sympathetics contract parasympathetics relax sphincter > - (smooth) > - external urethral somatic contract somatic relax sphincter > - - (skeletal) -PROSTATE Male Urethra Approx. 15-20 cm long Three parts (proximal to distal) Prostatic urethra (Widest and most dilatable portion) ○ Passes through prostate gland, receiving ejaculatory ducts from seminal vesicle glands, and prostatic ducts ↳ for semen Membranous urethra (Narrowest and least dilatable portion) ○ Passes through pelvic ﬂoor and deep perineal pouch ○ Surrounded by external urethral sphincter Penile (bulbous urethra) ○ Passes through bulb and corpus spongiosum of penis, ending at external urethral oriﬁce (meatus) where urine is released > - opening ○ Receives bulbourethral glands proximally ○ In glans (head) of penis, urethra dilates to form navicular fossa Male Urethral Constrictions & Catheterisation Urethra has two angles - infrapubic and prepubic angles ○ Holding penis upwards during catheterisation diminishes prepubic angle There are three constrictions ○ Internal urethral sphincter ○ External urethral sphincter ○ External urethral oriﬁce Female Urethra 15-20cm Relatively short - approx. 4cm males : ~ - Begins at neck of bladder Passes inferiorly through perineal membrane and muscular pelvic ﬂoor Opens directly onto perineum (in vestibule) ○ Within vestibule, urethral oriﬁce located anteriorly to vaginal opening (2-3cm posteriorly to clitoris) Distal end marked by presence of two mucous glands that lie either side of urethra (Skene's glands - homologous to male prostate) - ↳ release sexual fluids Why are women more susceptible to UTIs than men? Shorter urethra (4 cm in females vs 15-20 cm in males) - bacteria doesn’t have to travel far to reach the bladder Urethra is closer to anus - bacteria from faeces can inﬁltrate easily In pregnancy, uterus sits on top of bladder - can result in incomplete voiding of - - urine - Anal sphincters Internal anal sphincters: involuntary - Surrounds the superior ⅔ of the anal canal - Contraction stimulated and maintained sympathetically autonomically - External anal sphincter: voluntary - Attaches to the perineal body and posteriorly to the coccyx via the anococcygeal ligament - Bends superiorly with the puborectalis m. - Supplied by mainly S4 via the inferior rectal nerve Innervation of sphincters Motor control of internal urethral sphincter: - Sympathetic: L1-2 from superior + inferior hypogastric plexuses - Helps prevent seminal regurgitation into the bladder during ejaculation - Involuntary Motor control of external urethral sphincter: - Somatic: perineal branch of the pudendal nerve from the sacral plexus - Voluntary Defecation Reﬂex: store faeces defecation wall of rectum sympathetics relax parasympathetics contract > (smooth) - - internal anal sympathetics contract parasympathetics relax sphincter (smooth) > > - - external anal somatic contract somatic relax sphincter > > - (skeletal) - Arteries : From Internal Thoracic * Superior/Inferior Epigastric Artery supplies anterior abdominal wall , * Superior/Inferior Mesentric Arteries : From abdominal aorta supplies intestines (cecum colon) 2/3 and , , In the anal canal , separates upper The pectinate/dentate line - lower "3. - Demarcates the junction of the superior anal canal (endoderm/hindgut) & inferior anal canal (ectoderm/protoderm) Above pectinate line Below pectinate line Arterial supply Superior rectal artery (IMA branch) Middle rectal artery (internal iliac branch) Inferior rectal artery (internal pudendal branch) Venous drainage Internal haemorrhoidal plexus (drains to External hemorrhoidal plexus (drains to inferior + superior rectal vein → IMV) middle rectal veins → internal iliac vein → - Prone to varices due to portal common iliac v. → IVC) hypertension Lymphatic drainage Internal iliac → common iliac → lumbar Superﬁcial inguinal lymph nodes lymph nodes Nervous supply Inferior hypogastric plexus - only Inferior anal nerve (branch of pudendal nerve sensitive to stretch sensitive to touch, pain + temperature) Female Anatomy Female Reproductive System Anatomical Relations anterior retropubic space bladder vesicouterine pouch uterus rectouterine pouch (pouch of douglas) rectum posterior Types of Prolapse cystocele - bladder bulging into upper part of vaginal wall urethrocele - urethra bulging into lower anterior part of vaginal wall rectocele - rectum bulging into posterior part of vaginal wall uterine prolapse - uterus falling into the vagina Ovaries Three parts: ○ Surface ○ Cortex - where the follicles are (each follicle contains an oocyte) ○ Medulla - neurovascular network Function Produce oocytes (female gametes) Produce oestrogen and progesterone in response to LH and FSH Arterial Supply Paired ovarian aa. (come from abdominal aorta) and uterine a. Venous Drainage Left ovarian v. (→ left renal v.) Right ovarian v. (→ IVC) Lymphatic Drainage Para-aortic nodes Innervation Parasympathetic - uterine plexus Sympathetic - ovarian plexus Fallopian Tubes ↑ Four parts (lateral to medial) ○ Fimbriae - ﬁnger-like, ciliated projections which capture the ovum from the surface of the ovary ○ Infundibulum - funnel-shaped opening near the ovary to which ﬁmbriae are attached ○ Ampulla - widest section of tube (fertilisation usually occurs here) ○ Isthmus - narrow section of tubes connecting ampulla to uterine cavity - Fallopian Tubes Function Assists in transfer and transport of ovum from ovary to uterus: 1 - Inner mucosa lined with ciliated columnar epithelium and peg cells (waft ovum towards uterus and supply it with nutrients 2 - smooth muscle layer contracts to assist transportation of ovum Arterial Supply Uterine and ovarian aa. Venous Drainage Uterine and ovarian vv. Lymphatic Drainage Iliac, sacral and aortic nodes Innervation Sympathetic and parasympathetic - ovarian and uterine plexuses Sensory afferent ﬁbres - T11-L1 Uterus Three parts: ○ Fundus - where the fallopian tubes enter ○ Body - where the blastocyst implants ○ Cervix Function Where the foetus grows during pregnancy Arterial Supply Uterine a. Venous Drainage Plexus in broad ligament (→ uterine vv.) Lymphatic Drainage Iliac, sacral, aortic and inguinal nodes Innervation Sympathetic - uterovaginal plexus (part of inferior hypogastric plexus) Parasympathetic - pelvic splanchnic nerves (S2-S4) Afferent ﬁbres - ascend through inferior hypogastric plexus to enter spinal cord via T10-L1 ﬁbres Uterus: Anatomical Position Normal adult uterus is: ○ Anteverted with respect to vagina (anteverted - rotated forward, towards anterior surface of body) ○ Anteﬂexed with respect to cervix (anteﬂexed - ﬂexed, towards anterior surface of body) Uterine Anatomical Position Abnormalities Uterus may not sit in it’s normal sport ○ Retroverted uterus sits directly above the vagina → it is more likely to prolapse into vagina Uterine Formation Abnormalities Abnormalities can occur when the mullerian tubes don’t fuse together, or fuse together improperly or incompletely This can cause issues with pregnancy ○ E.g. in a bicornuate uterus the zygote · baby might implant here can implant in the lining of the uterus but there isn’t enough room for the baby to grow so it will likely result in a miscarriage Hysterectomy Types of surgeries ○ Partial (sub-total) - removal of body of uterus only (cervix left behind) ○ Total - removal of uterus and cervix ○ Radical - removal of uterus and cervix, parametrium, vaginal cuff, fallopian tubes (part or whole), (ovaries - depends on patient’s age) Methods ○ Abdominal ○ Vaginal ○ Laparoscopic Structures divided in a total hysterectomy: transverse cervical (cardinal) ligaments uterosacral ligaments pubocervical ligaments ovarian ligaments round ligaments of uterus broad ligaments of uterus uterovesical folds uterine tubes and uterine blood vessels uterine cuff What structure is at greatest risk of being damaged in a total hysterectomy? under uterine artery -. under gonadal artery (bifurca- · artery OVER common iliac ureter · ‘water under the bridge’ - ureter runs under uterine artery Cervix Connects vagina with uterus (acts as gateway) Two regions: ectocervix & endocervix Two openings: external os & internal os Function Facilitates passage of sperm into uterus Maintains sterility of upper repro tract Arterial Supply uterine a. Venous Drainage Plexus in broad ligament → uterine vv. Lymphatic Iliac, sacral, aortic and inguinal nodes Drainage Innervation Sympathetic - inferior nerve ﬁbres of uterovaginal plexus (part of inferior hypogastric plexus) Vagina Fibromuscular tube which is normally collapsed (walls touch each other) Function Sexual intercourse Childbirth Menstruation Arterial Supply Uterine and vaginal aa. (from internal iliac a.) Venous Drainage Vaginal venous plexus (→ uterine v. → internal iliac vv.) Lymphatic Drainage Superior part - external iliac nodes Middle part - internal iliac nodes Inferior part - superﬁcial inguinal nodes Innervation (mainly Parasympathetic & sympathetic - uterovaginal nerve plexus (part of inferior autonomic) hypogastric plexus) Inferior 1/5th of vagina has somatic - deep perineal nerve (branch of pudendal n.) Vaginal Fornices Fornices - potential spaces between vaginal part of cervix and vaginal walls **Posterior fornix is deeper Vulva Vulva = collective term for external female genitalia ○ Mons pubis - fusion of labia majora, subcutaneous fat pad anterior to pubic symphysis ○ Labia majora - two hair-bearing external skin folds ○ Labia minora - two hairless skin folds, lie within labia majora ○ Vestibule - area enclosed by labia minora (contains openings of other glands ; vagina and urethra) Skene's gland- ↑ lubricates ○ Bartholin’s glands - secrete lubricating mucus during sexual urethral opening arousal, located either side of vaginal oriﬁce ○ Clitoris - located under clitoral hood, formed of erectile corpora cavernosa tissue, which becomes engorged with blood during sexual stimulation m Vulva Vulva = collective term for external female genitalia ○ Mons pubis - fusion of labia majora, subcutaneous fat pad anterior to pubic symphysis ○ Labia majora - two hair-bearing external skin folds ○ Labia minora - two hairless skin folds, lie within labia majora ○ Vestibule - area enclosed by labia minora (contains openings of vagina and urethra) ○ Bartholin’s glands - secrete lubricating mucus during sexual arousal, located either side of vaginal oriﬁce ○ Clitoris - located under clitoral hood, formed of erectile corpora cavernosa tissue, which becomes engorged with blood during sexual stimulation :UterovaginalPlexusgastric plexus) PLEXUS IMPORTANT Vulva Function Sensory tissue during sexual intercourse Directs ﬂow of urine during micturition Protects internal female repro tract from infection Arterial Supply Paired internal and external pudendal aa. (branches of internal iliac a.) Venous Drainage Pudendal vv. Lymphatic Drainage Superﬁcial inguinal nodes Innervation Parasympathetic (clitoris and vestibule) - cavernous nerves from uterovaginal plexus Sensory nerves Anterior - ilioinguinal nerve, genital branch of genitofemoral nerve Posterior - pudendal nerve, posterior cutaneous nerve of thigh = Ovary : Ovarian artery + uterine artery (AND VEINS fallopian tube : Ovarian artery + uterine artery Blood Supply Summary uterusuterinateCartery Vulva : internal and external pudendal arteries fallopian ovaries uterus cervix vagina vulva tubes paired ovarian paired internal arterial aa. (arise from uterine and uterine & uterine a. and external supply abdo. aorta) & ovarian aa. vaginal aa. pudendal aa. uterine a. paired ovarian vv. (left drains vaginal venous venous uterine & plexus in broad ligament → into left renal v., plexus (→ pudendal vv. drainage ovarian vv. uterine vv. right drains into uterine v.) IVC) Blood Supply Summary Ligaments Associated Structures Ligaments Peritoneum associated Broad ligament (three divisions) with uterus & ovaries Mesometrium Mesovarium Mesosalpinx Ovaries Ovarian ligament Suspensory ligament of ovary Uterus Round ligament Cardinal ligaments Pubocervical ligaments Uterosacral ligaments **the following ligaments are contained within the broad ligament: ovarian ligament, round ligament, suspensory ligament of ovary Broad Ligament - Three divisions: Mesometrium Surrounds uterus and is largest subsection Runs laterally to cover external iliac vessels, forming distinct fold over them Encloses proximal part of round ligament of uterus Mesovarium Associated with ovaries Projects from posterior surface of broad ligament and attaches to hilum of ovary, enclosing neurovascular supply Doesn't cover surface of ovary itself Mesosalpinx Originates superiorly to mesovarium Encloses fallopian tubes Ligaments Associated with the Ovaries: Ovarian Ligament Connects inferior side of ovary to side of uterus, just below origin of fallopian tubes Structurally, ﬁbrous band of tissue that lies within broad ligament Suspensory ligament of Extends outwards from ovary to lateral abdominal wall ovary (aka Consists of fold of peritoneum - located within broad infundibulopelvic ligament) ligament Function - contains ovarian vessels and nerves (ovarian artery, ovarian vein, ovarian nerve plexus and lymphatic vessels) Ligaments Associated with the Uterus: Round Ligament Remnant of embryonic gubernaculum Originates at uterine horns (where fallopian tube enters uterus), passes through inguinal canal, attaches to labia majora Located inside broad ligament Cardinal Ligaments Situated along inferior border of broad ligament House uterine artery and uterine veins Travels from side of cervix to lateral pelvic wall at level of ischial spines Pubocervical Ligaments Bilateral structures Attach cervix to posterior surface of pubic symphysis Uterosacral Ligaments Bilateral ﬁbrous bands Attach cervix to sacrum Male Anatomy Pathway of sperm during ejaculation 1. Seminiferous tubules 2. Epididymis 3. Vas deferens 4. Ejaculatory ducts 5. Urethra 6. Penis Penis - Common outlet for urine & semen - Consists of: root, body & glans - Composed of 2 cylindrical cavernous bodies of erectile tissue: - 2 corpus cavernosa - 1 corpus spongiosum - Tunica albuginea = outer ﬁbrous covering of each cavernous body - Deep fascia of the penis/Buck’s fascia = superﬁcial to outer covering - Forms a strong membranous covering for the corpus cavernosa & corpus spongiosum binding them together Penis - Penis root: - Located in superﬁcial perineal pouch - Contains 3 erectile tissue: 2 crura + 1 bulb & 2 muscles (ischiocavernosus & bulbospongiosus) - Penis body: - Free part suspended from pubic symphysis - Composed of 3 cylinders of erectile tissue - Penis glands: - Formed from distal expansion of corpus spongiosum - Contains external urethral oriﬁce (opening of spongy urethra near penis tip) Penis - erectile tissue > Colles' - fascia 1. Corpus cavernosa a. Formed by 2 crura meeting at the midline 2. Corpus spongiosum & ↳ Buck's fascia a. Is the tapered part of the bulb of the penis in the penis body ↳ In both penis and testes , and scrotum. 3. Bulb of the penis a. Fuses midline into a single unilateral structure 4. Glans penis a. Corpus spongiosum that has greatly expanded distally Penis - ligaments Suspensory ligament of the penis - Condensation of deep fascia - Attached to penis at junction of its root + body - Arises from the anterior surface of the pubic symphysis Fundiform ligament of the penis - Condensation of collagen & elastic ﬁbres of subcutaneous tissue - Surrounds the penis + unites with the dartos fascia Penis - vasculature - Arterial supply: - Dorsal & deep arteries of the penis - Arteries of the bulb of the penis (bulbourethral a.) - Venous drainage: - Blood from cavernous spaces is drained by venous plexuses - Deep dorsal veins of penis → prostatic venous plexus → cavernous spaces - Superﬁcial dorsal veins drain skin + subcutaneous tissue → superﬁcial external pudendal v. - Innervation: - Parasympathetic from S2-4 spinal cord segments via: - Pelvic splanchnic nn. - Pudendal nn. - Sensory + somatic innervation by: - Dorsal nerve of the penis - Pudendal n. The scrotum - Fibromuscular cutaneous sac - Located between the penis + anus - Arterial supply: anterior + posterior scrotal arteries - Venous drainage: scrotal v. (derivative of the external pudendal v. - Lymphatic drainage: superﬁcial inguinal lymph nodes - Innervation: - Anterior scrotum = lumbar plexus derivatives (ilioinguinal n. & genital branch of genitofemoral n. ) * - Posterior scrotum = sacral plexus derivatives (posterior scrotal nn. & superﬁcial branches of pudendal n.) - Sympathetic ﬁbres = assist in thermoregulation of testes - Stimulates contraction of dartos muscle or scrotal sweat glands Testes & epididymis - Testes & epididymis are paired structures within the scrotum - Both are suspended from the abdomen by the spermatic cord - Testes → site of sperm production + hormone synthesis - Epididymis → storage of sperm - Is posterolateral on each teste Testes - Functions: spermatogenesis + androgen (testosterone) production - Has lobules containing seminiferous tubules supported by interstitial tissue - Seminiferous tubules are lined by Sertoli cells that aid in sperm maturation - Spermatozoa are produced here - Developing sperm travels through the tubules and collect in the rete testis - Inside the scrotum, the testes are mostly covered by the tunica vaginalis - Tunica vaginalis lubricates surface of testes + allows friction-free movement (as it contains some viscous ﬂuid) - Testicular parenchyma is protected by tunica albuginea (ﬁbrous capsule that encloses the testes + divides it into lobules) S eferens ⑮ => of epididymis stia & Sta #bules Tunica albugirina · nica vaginalis - Siniferous tubules A Testes - Have an optimal temperature of 34 degrees Celcius, which is maintained by a range of factors: - Embryological descent of the testes via the inguinal canal - Cremaster muscle (raises the testes in response to cold, sex or fear) - Formed by the internal oblique muscle - Innervated by genital branch of the genitofemoral nerve (L1-L2) - Dartos muscle (smooth muscle which changes surface area of scrotum to regulate temperature → wrinkles the testes) - Receives autonomic innervation - Pampiniform plexus of testicular veins Epididymis - Is a single heavily coiled duct - Can be divided into: - Head → most proximal part - Body - Tail → marks the origin of the vas deferens - Main roles: Sperm maturation & storage - The epididymis is a common site of inﬂammation in males due to untreated infection by: Neisseria gonorrhoea & Chlamydia trachomatis Testes + epididymis vasculature Cremasteric artery : Testicular artery + * Main arteries - Innervation: from the testicular plexus * Main nerve : Testicular Plexus * Main Veins : PAMPINIFORM PLEXUS - Derived from the renal + aortic plexi - Receives autonomic + sensory ﬁbres - Vasculature supply: testicular arteries (arise directly from the abdominal aorta) - Descend down the abdomen and pass into the scrotum via the inguinal canal - Are contained within the spermatic cord - Testes are also supplied by branches of cremasteric artery (from inferior epigastric a.) - Venous drainage: testicular veins - Formed from the pampiniform plexus in the scrotum - Pampiniform plexus is a network of veins around the testicular a. - Lymphatics: lumbar + para-aortic nodes Testicular vasculature - Arterial supply - Testicular arteries which arise from the abdominal aorta inferior to the renal arteries - Venous supply - Pampiniform venous plexus that comes from the testicular vein (note that the LHS testicular vein comes from the left renal vein due to the IVC being on the RHS) - Lymphatic drainage - Follows testicular a. & v. to the right and left lumbar & pre-aortic lymph nodes Descent of the testes Timing: 7th-12th week Location: Posterior body wall & perineum Key outcomes: relocation and development of inguinal canal - The testes originate as an indifferent gonad on the posterior abdominal wall - As the abdominal cavity starts to grow, the testes descend closer to their pelvic location - The testes push into the pelvic region partially via the gubernaculum - The gubernaculum starts to shorten into the scrotal ligament (is what pulls the ligament down) - As it shortens, we pull the testes from the posterior abdominal wall and push through the anterior abdominal wall so they sit retroperitoneally Descent of the testes The testes will descend posterior to the processus vaginalis - Processus vaginalis is an embryonic developmental outpouching of the peritoneum - It precedes the testes and then closes (if it doesn’t close, potential for a hernia!) Descent of the testes As the testes descend, they drag layers of peritoneum down with them. However, the transversus abdominis muscle arches too high for the testes to capture a layer of it (won’t be dragged!). Every other layer will be dragged down. Layers Abdomen Perineum Scrotum Camper’s fascia Fatty layer of superficial fascia Dartos m. (male) Labia majora (female) Scarpa’s fascia Colle’s fascia (membranous layer of Dartos muscle superficial fascia) External oblique muscle External spermatic fascia Becomes Buck’s fascia at the penis Internal oblique muscle Cremaster muscle Transversalis fascia Internal spermatic fascia Spermatic cord Formed at the opening of the inguinal canal (deep inguinal ring) → inguinal canal → superﬁcial inguinal ring and continues into the scrotum. It is a collection of vessels, nerve and ducts that run to and from the testes. * 3 cremasteric , : artery nerve , fascia cremasteric deferential, * 3 arteries testicular , : nerve genitofemoral Contents: * Main : nerve - 3 arteries: testicular a., deferential a., cremasteric a. - 3 nerves: genital branch of the genitofemoral n., cremasteric n., sympathetic nerve ﬁbres - 3 fascias: external spermatic fascia, cremasteric fascia, internal spermatic fascia -vein - 3 other things: vas deferens, pampiniform plexus, lymphatic vessels Varicocele - When the pampiniform plexus of veins become dilated (varicose) + tortuous - Is usually visible only when a man is standing or straining - Disappears while supine as gravity can empty the veins - Can form from: - Defective valves from the testicular region - Kidney or renal vein problems causing distension - Occurs predominantly on the LHS because of the acute angle at which the right vein enters the IVC (right vein is more favourable to ﬂow) - On the LHS, the left testicular vein enters the left renal vein at a 90 degree angle so it is more susceptible to obstruction Haematocele of Testes - Collection of blood in the tunica vaginalis - Results from the rupture of branches of the testicular artery by trauma to the testes - Trauma can cause scrotal or testicular haematoma - Haematoma = accumulation of blood in an extravascular location Testicular torsion - Twisting of the spermatic cord due to rotation of the testicle within the scrotum associated with a poorly secured testes - Surgical emergency due to necrosis of the testes that may occur 6-12hrs after - Torsion will obstruct: - Venous drainage - Results in oedema + haemorrhage - Spermatic cord twisting will strangulate the testicular artery → necrosis - Clinical ﬁndings: - Severe testicular pain +/- pain in lower abdomen - Nausea & vomiting - High-riding testes - Absent - cremasteric reﬂex Testicular cancer - Most common solid malignancy in males of 20-35 years old - Risk factors: - Cryptorchidism - Contralateral testicular cancer - Family history - Clinical features - Gynecomastia - Painless testicular nodule or swelling - Negative transillumination test light is shone when a ↑ no through light passes Testicular vs scrotal vs prostate cancer spread Testicular Lung and lymph nodes of the chest, pelvis - and base of the neck Scrotal Superﬁcial inguinal Prostate Batson’s venous plexus (vertebrae + brain) Vas deferens - Is a continuation of the epididymis duct - Has a relatively thick muscular wall - Thus has a cord-like ﬁrmness - Begins in the tail of the epididymis at inferior pole of testis - Ascends posterior to testes & medial to epididymis - Crosses over external iliac vessels to enter pelvis - Passes medial to the ureter - Ends by joining the duct of the seminal glands to form the ejaculatory duct Arterial supply: artery to the vas deferens (usually arises from superior vesical a.) Venous drainage: testicular vein Seminal glands/vesicles - Elongated structure between bladder fundus + rectum - Do not store sperm - Secrete a thick alkaline ﬂuid (contains fructose) that mixes with sperm as it passes into the ejaculatory ducts & urethra - Lies posterior to ureters Arterial supply: arteries to seminal glands (derived from inferior vesical & middle rectal aa.) Venous drainage: veins accompany arteries with similar names Ejaculatory ducts - The ejaculatory duct is formed by: vas deferens + seminal glands - Arise near the bladder neck Arterial supply: arteries to the vas deferens (arise from superior vesical aa.) Venous drainage: veins draining vas deferens join the prostatic and vesical venous plexuses and seminal The prostate gland prostate * Ejaculate fluid from vesicles (MINUS Sperm) - Surrounds the prostatic urethra - Has 2 parts: glandular & ﬁbromuscular - Adds a slightly alkaline secretion (rich in citrate, calcium + enzymes) to sperm ejaculate Lobes of the prostate - Isthmus: seminal - Anterior to urethra - vesicle - Contains little to none glandular tissue - Right & left lobes ↑ ejaculatory duct - Can be subdivided into 4 lobes The prostate gland The prostate gland is homologous to the female urethral + paraurethral glands which both arise from the urogenital sinus. Zones: 1. Central zone → surrounds ejaculatory ducts (25% of prostate volume) 2. Transitional zone → surrounds urethra (5-10% of prostate volume) a. This is what typically undergoes BPH 3. Peripheral zone → body of the gland + located posteriorly (65%) 4. Fibromuscular stroma → stimulated anteriorly + merges with tissue of the urogenital diaphragm The prostate gland Arterial supply: prostatic aa. (mainly branches of internal iliac a.) Venous drainage: veins join to form the prostatic venous plexus (also connects to the Batson venous plexus → internal vertebral venous plexus & to the vesical venous plexus) Innervation: inferior hypogastric plexus (SNS, PNS + sensory) - Prostate is ﬂanked by neurovascular bundles which supply the penis for erection → may be damaged in a radical prostatectomy - Motor control of smooth muscles in the prostate + seminal vesicles in emission = sympathetic - Prostate gland secretion = parasympathetic (pelvic splanchnic) Benign prostatic hyperplasia - Benign growth of cells in the transitional zone of the prostate - Leads to the formation of a smooth, elastic & ﬁrm nodule → Slit-like prostatic urethral - compression → Bladder outlet obstruction → Obstructive symptoms of BPH - Prevalence increases with age - Bladder outlet obstruction leads to: - Detrusor overactivity - Weakening of the bladder wall → incomplete voiding & predisposition to UTIs - Results in: - Voiding problems: hesitancy, poor stream & dribbling - Storage problems: frequency, urgency & nocturia - Diagnosis: enlarged look for prostate - Digital rectal exam >- - Prostate speciﬁc antigen levels → increased free PSA lvls Bulbourethral glands The male bulbourethral glands (or Cowper’s glands) are a paired structure that is homologous to the female greater vestibular glands. These both arise from the urogenital sinus. - Note that these are determined by the presence of DHT in males - Secretes lubrication (also neutralises acid from urine) - Is embedded within the external urethral sphincter Nervous innervation of the erectile tissues Autonomic: parasympathetic + sympathetic Somatic: pudendal nerve Innervation Result Parasympathetic Erection Sympathetic Emission, remission & ejaculation/orgasm Stimulates contraction of internal urethral sphincter to prevent retrograde ejaculation Somatic (pudendal) Maintaining erection/aid in ejaculation Erectile dysfunction Is the inability to achieve or sustain an erection sufﬁcient in rigidity or duration for sexual intercourse. Erection is driven by parasympathetic, sensory (dorsal nerve from pudendal) and sympathetic nerves. Common causes: - Hypertension, CVS disease, hyperlipidaemia, diabetes mellitus - Prostate surgery (damage to cavernous nerves) - Hypogonadism - Medications - Antihypertensives - Antidepressants - Dopamine antagonists - Alcohol abuse Perineal Muscles Perineal Muscles Muscles covering erectile tissues Two muscles ○ Bulbospongiosus Holds less blood Good for patency (good for structures that need to remain open) Thin connective tissue covering ○ Ischiocavernosus Hold more blood Good for turgidity / rigidity (erection needs Transverse Perineal Muscles blood pressure) Thick connective tissue (tunica albuginea) Two muscles ○ Deep Function - aid in maintaining erection ○ Superﬁcial ○ Stretch receptors triggered through erectile tissues becoming engorged with blood, Function muscles contract to pinch off veins that ○ Support pelvic ﬂoor and viscera normally drain erectile tissues ○ Help maintain intra-abdominal pressure Perineal Muscles Infertility Female infertility There are a few main causes of female infertility: - Ovary disorders - Fallopian tube issues - Problems in/with the uterus - Immune factors - Other causes (e.g. endometriosis, PCOS) Female infertility - diagnostics Assess ovulatory function: - Body temperature - Hormone tests - Mid-luteal serum progesterone level - Endometrial biopsy Assess patency of fallopian tubes & uterus - Hysterosalpingography: X-Ray procedure where contrast is injected to the uterus to indicate possible blockages + structural abnormalities Male infertility - causes GnRH - Gonadotropin Glow levels anosmia/ loss of Releasing ↳ small hormones Hormone of sex Lab investigations for male infertility - Semen analysis - Oligospermia = low sperm density - Azoospermia = no sperm seen - Serum FSH - Testicular histology - Genetic testing Male Reproductive Histology Seminiferous tubules Sertoli cells - Columnar cell with distinct-shaped nucleus - Cytoplasm is tall & thin and reaches from the basal lamina to the lumen - ‘Nurse’ cell of developing germ cells stimulated by FSH to produce spermatogenesis Sertoli cells > - - Lateral plasma membranes of adjacent Sertoli cells form specialised tight junctions - This is the blood-testes barrier * - Protects immature sperm from being removed by the immune system - Separates the epithelium into 2 compartments: - 1st diploid germ cells - 2nd is immune-privileged - Functions: - Expresses SRY on Y chromosome - Produces AMH in early stages of foetal life - Ensures self-renewal of spermatogonial stem cells Intertubular tissue - Loose connective tissue with vessels, nerves, lymphocytes, lymphatic system - Contains Leydig cells > produces testosterone - - Respond to LH from the anterior pituitary gland - Produces androgens which diffuse into seminiferous tubules and then can enter bloodstream * Sertoli cells : testes/blood barrier · produces luminal fluid for sperm mobility nucleus · tall , thin and distinct Spermatogenesis * leydig cells : · · between tubules respond to CH produces testosterone (androgens) (distinct nucleus ( The rete testes more the vas efferentia - Network of tubules between the seminiferous tubules & vas deferens. Is the passageway for the exit of sperm from the testes into the duct system seminiferous tubules ↓ vas efferentia ↓ was deferens > under the microscope pseudostratified - microvilli Epididymis : · coiled tubules sperm visible (immature sperm tool Black arrows are sperm undergoing their maturation process! Sperm might be stored in the epididymis for weeks and gain initial motility here. INFLAMMATION due to : 1 gonorrhea and chlamydia Vas deferens - Arises from the epididymal tubule with similar epithelium and a thicker smooth muscle wall (muscle helps contract to force sperm along this space during ejaculation) - After a vasectomy, sperm are phagocytosed by tissue adjacent to the lumen of the vas deferens Seminal vesicles - Contains pseudostratiﬁed columnar epithelium - Is a highly folded and ridged lamina propria + smooth muscle - Secretes yellow, viscous ﬂuid containing proteins + high prostaglandin Prostate gland - Contains ejaculatory duct & urethra - Is a capsule with ﬁbromuscular septa forming lobules - Testosterone stimulates its growth Female Reproductive Histology Ovaries -granulosa cells surrounding Almond-shaped (3cm x 1.5cm x fluid , granulosa multiplies 1cm) more - not if pregnancy does Simple squamous or cuboidal > - occur this becomes , outer epithelium ovary penis testes fluid filled , , ~ antrum : Tunica albuginea (thick connective - remnants of follicle , produces cavity progesterone tissue capsule) > - ruptures to release oocyte Cortex - mostly ovarian follicles at different stages of development Medulla - loose connective tissue with a rich blood supply Folliculogenesis ) ↓ granulosa cells Primary - cuboidal epithelium Antrum - space ﬁlled with ﬂuid (shaped like moon) Zona pellucida - surrounds oocyte in antral Corona radiata - bridge across antrum in graaﬁan follicle Graaﬁan = mature = tertiary = pre-ovulatory Y perucial After Ovulation Corpus luteum = yellow body Corpus albicans = white body IF PREGNANT IF NOT PREGNANT Fallopian Tubes 3 layers ○ Mucosa - simple columnar epithelium with ciliated cells and secretory cells ○ Lamina propria - loose connective tissue ○ Muscularis - inner circular and outer longitudinal layers of smooth muscle - simple columnar-ciliated and secretory Uterus 3 layers ○ Outer serosa / adventitia (connective tissue) ○ Myometrium - thick layer of smooth muscle ○ Endometrium - the mucosa Epithelium - simple columnar epithelium with ciliated cells Lamina propria - contains simple tubular glands in connective tissue Can also be subdivided into Functionalis - part of endometrium that is shed during menstruation Basalis - part that is retained during menstruation (furthest from lumen) # Stratum functionale sheds during menstruation > - produced by corpus lute um secreted by growing Ovarian follicles SUMMARY : MALE ANATOMY. PENIS 1 - Root , Body , Glans - 2 Corpus Carvenosa and 1 Corpus Spongiosum Tunica Albuginea (covers each cavernosal : Fascia Colles' Fascia : Superficial Buck's Fascia : Deep and binds the two corpus together Root : · IN Superficial Perineal Douch - 2 crura and I bulb - 2 Erectile muscles : Ischiocavernosus + Bulbospongiosus Body : - 3 cylinders of erectile tissue : 2 corpus cavernosum + 1 corpus spongiosum Glans : - Expansion of CORPUS SPONGIOSUM - Opening of urethra LIGAMENTS : Suspensory + Fundiform Y ASCULATURE : Arteries : Arteries of the penis Bulbourethral artery Veins : Venous plexuses (Veins of penis) Drain to sup ext.. pudendal vein INNERVATION : Parasympathetic S2-54 - Pelvic Splanchnic nerve - Pudendal neuve Sensory/Somatic - Dorsal nerve of pen is - Pudendal neuve. SCROTUM 2 Sex Differentiation How does sex differentiation occur? Y chromosome → SRY protein → gonads → hormones → duct degeneration → genitalia formed male female bipotential gonads SRY gene --> SRY Testes formed Absence of SRY gene Ovaries formed proteins wolfﬁan duct Presence of testosterone Forms seminal vesicles, Absence of Degenerates vas deferens, epididymis testosterone mullerian duct Presence of AMH (anti Degenerates Absence of AMH (anti Forms repro tract mullerian hormone) mullerian hormone) Sex Differentiation: Sex Differentiation: Presentation of a male with 5 alpha hydroxylase deﬁciency internal male genitalia external female genitalia Normally: testosterone ----- 5 alpha hydroxylase -----> DHT (dihydrotestosterone) DHT → development of external male genitalia CAH - Congenital Adrenal Hyperplasia CAH - congenital adrenal hyperplasia three forms ○ classic, salt wasting females - ambiguous genitalia, low cortisol and aldosterone signs males - failure to thrive, dehydration, hyponatraemia, hyperkalaemia ○ classic, non-salt wasting (simple virilising) usually in males early virilisation (2-4 yrs - growth spurt, pubic hair, adult body odour) females - genital ambiguity ○ nonclassic, late onset early pubarche young women - hirsutism and menstrual irregularity males may be asymptomatic Most common cause of CAH most common cause - 21 hydroxylase deﬁciency (autosomal recessive condition - need two parents with CAH or carriers) ○ enzyme involved in producing aldosterone and cortisol in adrenal glands ○ substances used to form aldosterone and cortisol build up and are converted to androgens other causes: 11 beta hydroxylase deﬁciency, 17 alpha hydroxylase deﬁciency CAH Treatment maintenance therapy ○ glucocorticoids (usually hydrocortisone - replacement for cortisol) during periods of stress need greater amounts suppresses ACTH overproduction (reduces stimulation of androgen pathway) switch to prednisolone or dexamethasone in adults ○ salt-wasting form requires ﬂudrocortisone (mineralocorticoid) and sodium chloride use of this may decrease with age ○ growth hormone therapy in children (CAH associated with short stature in adults) over treatment can lead to iatrogenic Cushing’s syndrome reconstructive surgery ○ for females with ambiguous genitalia Male reproduction Ovarian and menstrual cycles Physiology Menopause Puberty Fertilisation and early life Placentation and foetal growth Birth Male Reproduction Dual function of the testes The testes have 2 main functions of: 1. Spermatogenesis 2. Androgen (testosterone) production Note that fertility does not mean virility. - Fertility = ability to reproduce - Virility = activity of the androgen hormones & how they affect structure, function & psychology of the body Hypothalamic-pituitary axis Notes: - GnRH production is pulsatile - LH, FSH, TSH, HSG (placenta pregnancy hormone) are glycoprotein hormones which share a common subunit * LH : Stimulates Leydig cells in the testes to produce TESTOSTERONE Stimulated by Hormones & testicular function * Sertoli cells : - FSH - Produces inhibin - Inhibin turns down FSH prod. - When sperm is made (under the inﬂuence of FSH + testosterone), the sertoli cell supports sperm production & makes inhibin B - Inhibin B turns down FSH production - The testicle will also regulate sperm production via an androgen negative feedback loop - LH stimulates testosterone production - Testosterone feedback will inhibit anterior pituitary and the hypothalamus Spermatogenesis - The process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testes - Requires development of Sertoli & germ cells under the inﬂuence of foetal neonatal and pubertal gonadotropin surges - Both LH + FSH act on Sertoli cells - LH → acts on the androgen receptor of Sertoli cells - FSH → acts on the surface receptor of Sertoli cells Sperm structure > - a female hormone but in males helps with bone health cognitive , function etc. Testicular failure (hypogonadism) Primary testicular failure - Testes have been damaged and are not working (hypergonadotropic - Insufﬁcient sex steroid production in gonads hypogonadism) - Less feedback hormone from inhibin B so levels of FSH & LH won’t be downregulated (will be HIGH) Secondary testicular failure - The gonad is a victim to the (hypogonadotropic hypothalamus-anterior pituitary not doing its hypogonadism) ‘job’ - There is insufﬁcient GnRH/gonadotropin release - Levels of testosterone, LH + FSH will be low Congenital GnRH deﬁciency therapy - To establish fertility: gonadotropin therapy - To establish virilisation: testosterone therapy The aim is to mimic normal puberty: 1. Introduce LH a. Starts process of testosterone coming & growth in testes b. Lasts 4-6 months 2. Add FSH a. Further 3-24 months 3. Natural fertility or IVF results Onset of puberty GnRH Hypothalamus releases ↓ (H and FSH Pituitary releases - Pulsatile GnRH pulses from hypothalamic neurons ↓ testosterone - Initially only nocturnal, then throughout Leydig cells produce - Triggered by multiple genes ↓ Vivilization - Rising LH → Leydig cells secrete testosterone - Virilisation process begins testosterone : - Testicular growth # Metabolites of Estradiol - Metabolites of testosterone are important o · DHT - Estradiol - Bone maturation + epiphyseal closure - Some breast development (gynaecomastia) common - Dihydrotestosterone - Activity in hair follicles, sebum secretion, prostate Testosterone Testosterone can exert its effects via 3 hormones and 3 main pathways: Ampliﬁcation pathway (prostate, skin): F 1. DHT (converted by 5alpha-reductase) → androgen receptor Samara reductase 1 Amplification pathway : DHT (by Testosterone ANDROGEN RECEPTORS 2. Testosterone (direct pathway) → androgen receptor. 2 Diversification pathway : Estradio-OESTROGEN RECEPTOR RENAL. 3 Inactivation pathway : HEPATIC OXIDATION and EXCRETION Diversiﬁcation pathway (brain, bone): 3. Estradiol (converted by aromatase) → oestrogen receptors Inactivation pathway 4. Hepatic oxidation & conjugation with renal excretion Age-related changes in testosterone Male reproductive ageing is associated with a decline in serum testosterone. - Is a gradual + relatively modest change - There is a considerable variability between men - Note that there is NO male menopause Ovarian and Menstrual Cycle The ovarian cycle - overview The ovaries: - Produce gametes during the foetal period (oogenesis) & hormones (oestrogen, progesterone & inhibin) - Ovaries contain 1-2 million eggs (oocytes) at birth (most of these degenerate during development - Throughout their life in the ovaries, oocytes exist in structures known as follicles - Only about 400 oocytes are released during a woman’s lifetime The ovarian cycle: - Series of changes in the ovary involving: - Follicle maturation - Ovum being shed - Corpus luteum developing Phases of the ovarian cycle 1. Follicular phase (d1-14) a. Follicle growth with ovulation at the end of this stage 2. Luteal phase (d15-28) a. Period of corpus > - luteum activity produces progesterone Stages of the ovarian cycle - Stage One: - Primordial follicles = earliest follicle type - Are one primary oocyte arrested in prophase I surrounded by a single layer of granulosa cells - Each month (from puberty to menopause) some primordial follicles will be recruited or activated via signals from oocyte, granulosa cells + ovarian stroma cells - Stage Two: - Once activated, the primordial follicle changes: - Cells surrounding the oocyte become cuboidal - Oocyte enlarges - Zona pellucida forms - The primordial follicle now becomes the primary follicle Stages of the ovarian cycle - Stage Three: - Granulosa cells proliferate to form a stratiﬁed epithelium around the oocyte - Follicles are now in the preantral stages - Inner layer of the granulosa cells are closely associated with the oocyte via gap junctions - Gap junctions allow ions, metabolites + signalling molecules to pass - Gives a form of bidirectional development so the granulosa & oocyte can guide each other’s development - Connective tissue cells surrounding the granulosa cells differentiate and form layers of cells known as the theca - Theca + granulosa cells → produce oestrogen - Inner thecal cells produce androgens - Granulosa cells convert the androgen to oestrogen Stages of the ovarian cycle - Stage Four: - A ﬂuid ﬁlled space begins to form in the midst of the granulosa cells - Is a result of the follicular ﬂuid the granulosa cells secrete - Fluid coalesces to form a large ﬂuid-ﬁlled cavity known as the antrum - The resulting follicle is now called an early antral follicle - At the beginning of each menstrual cycle, 10-25 of the pre-antral and antral follicles begin to develop into larger antral follicles - Only 1 of the larger antral follicles known as the dominant follicle, will continue to develop - Is selected due to the amount of oestrogen produced in that follicle Stages of the ovarian cycle - Stage Five: - The non-dominant follicles that had begun to enlarge undergo atresia - Atresia = type of apoptosis - Occurs at every stage of follicular genesis (not just larger follicles) - Eggs in the degenerating follicles also die - Stage Six: - Antrum of the dominant follicle continues to expand with follicular ﬂuid until eventually the oocyte together with its surrounding capsule of granulosa cells form a mound (cumulus oophorsu) that projects into the antrum - The cumulus-oocyte complex will eventually separate from the follicle wall and ﬂoat in the antral ﬂuid Ovulation 1. The mature follicle becomes so large it bulges from the external ovarian surface a. Ovulation occurs when the walls of the follicle + ovary rupture at the site where they have joined 2. Ovulation expels the secondary oocyte + surrounding cumulus cells into the peritoneal cavity a. Occurs around d14 of the menstrual cycle b. Follicular ﬂuid: i. Provides a medium to carry the oocyte from the ruptured follicle → fallopian tube ii. Offers protection + nourishment to oocyte at this time 3. The cumulus-oocyte-complex is swept up by the ﬁmbriae into the fallopian tube a. In the ovary, the ruptured follicle collapses around the antrum i. Undergoes rapid transformations The corpus luteum - Forms in the ovary from the remnants of the ovulating follicle - Comprises of enlarged granulosa + thecal cells - Secretes progesterone + oestrogen - Duration if pregnancy occurs: 3 months - Degenerates after 10 days if no pregnancy occurs - Eventually forms the corpus albicans (scar/white body) - Loss of corpus luteum results in menstruation + beginning of a new ovarian cycle Hormonal control of ovarian function Main hormones controlling the ovarian cycle: - GnRH - Anterior pituitary gland gonadotropins - FSH & LH - Oestrogen - Inhibin - Progesterone The uterine cycle A series of cyclic changes the uterine endometrium goes through each month in response to the waxing and waning of ovarian steroid hormones in the blood. > - What is shed What isn't shed vasoconstricted > - so that stratum functionalis sloughs off Phases of the uterine cycle Day 1-5: Menstrual phase (menses): - Shedding of the functional layer of the endometrium - Prostaglandin levels increase and cause vasoconstriction of spiral arteries and uterine contractions - Without oxygen + nutrients from blood, endometrial cells die and the stratum functionalis sloughs off ↳ superficial Layer - The detached tissue + blood pass out through the vagina as the menstrual ﬂow > stratum basalis - - All but the deepest layer of the endometrium is shed - Oestrogen + progesterone levels are low oestrogen and progesterone * Pregnancy glow is due to Phases of the uterine cycle Day 6-14: proliferative (preovulatory) phase - Rebuilds functional layer of the endometrium - Due to proliferation of: glandular epithelial cells, stroma & blood vessels - Endometrium becomes thick & well vascularised - Oestrogen levels rise A M4 - Promotes progesterone receptor expression on endometrial cells - Thins the cervical mucus - - Ovulation occurs at the end of this phase Phases of the uterine cycle Day 15-28: Secretory (post-ovulatory phase) - Progesterone levels rise rapidly & prepare the endometrium for implantation - Glands & stroma enlarge, arterioles elongate and nutritious glycogen is secreted into the uterine lumen - Progesterone causes cervical mucus to thicken - Also inhibits prostaglandin-induced contractions of the myometrium to ensure a good environment for implantation If fertilisation doesn’t occur, the corpus luteum degenerates and progesterone levels fall # granulosa cells + theca cells > - oestrogen ↓aromatase enzyme estradiol Polycystic Ovary Syndrome (PCOS) Common disorder in women characterised by hyperandrogenism, ovulatory dysfunction and/or polycystic ovarian morphology. There are a number of different characteristic features which can lead to different phenotypes. Main PCOS characteristic features 1. Dermatological abnormalities (caused by hyperandrogenism) a. E.g. Acne 2. Metabolic dysfunction a. Increased insulin resistance in the muscle & liver → leads to hyperinsulinemia (increased insulin secretion) 3. Subfertility a. Infertility is higher in patients in PCOS Ovarian Axis Hypothalamic Pituitary - - GnRH Hypothalamus releases ↓ GnRH acts on pituitary ↓ IH and FSH Pituitary releases ↓ Ovary responds by producing estradiol , inhibin B inhibin A and ↓ 4 feedback : Estradiol Negative ↓ GURH YFSHYLHY OR Estradio ↓ A4 Inhibin BT Inhibir ↓ LH ↓ FSH ↓ GnRHY ↓ LH4 PCOS - pathophysiology ↓ AndrogenY ↓ GnRH

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