Embryology. Development of the Urogenital_2024 2.pptx

XY2141. Embryology. Embryogenesis of the urogenital system Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES EMBR.08 - Urogenital System EMBR.08.01 - Explain the embryologica...

XY2141. Embryology. Embryogenesis of the urogenital system Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES EMBR.08 - Urogenital System EMBR.08.01 - Explain the embryological sources of the urinary system EMBR.08.02 - Explain how each of the 3 versions of the kidney help form the mature kidney EMBR.08.03 - Explain the embryological development of the mature kidney EMBR.08.04 - Explain the ascent of the kidneys and their clinical correlations EMBR.08.05 - Explain the development of the ureter and its clinical correlations EMBR.08.06 - Explain the development of the bladder and the clinical correlations EMBR.08.07 - Explain the development of the trigone of the bladder EMBR.08.08 - Explain the development of the suprarenal gland and its clinical correlation EMBR.08.09 - Explain the embryological sources of the male and female reproductive system EMBR.08.10 - Explain the differences between the paramesonephric and mesonephric duct in the development of the reproductive systems EMBR.08.11 - Explain the formation/components of testes and descent of the testes and clinical correlations EMBR.08.12 - Explain the formation/components of ovaries and descent of the ovaries EMBR.08.13 - Explain the formation of male external genitalia and clinical correlations EMBR.08.14 - Explain the formation of female external genitalia and clinical correlations EMBR.08.15 - Explain the formation of the female reproductive organs their clinical correlations EMBR.08.16 - Explain the genital clinical correlations  OVERVIEW Urinary system consists of: kidneys, ureters, urinary bladder, urethra. Urinary system develops from intermediate mesoderm and primitive cloaca. Development begins at the 4th week of embryonic development. Precursor cells migrate from cranial to caudal end. FOLDING OF THE EMBRYO Intermediate mesoderm FOLDING OF THE EMBRYO  UROGENITAL RIDGE After folding of embryo the intermediate mesoderm forms a longitudinal elevation of mesoderm along the dorsal body wall on each side of dorsal aorta/dorsal mesentery of gut called urogenital ridge. Medial part of urogenital ridge that gives rise to the genital system is called genital ridge. Lateral part of urogenital ridge that gives rise to the urinary system is called nephrogenic cord. UROGENITAL RIDGE FOLDING OF EMBRYO AND FORMATION OF THE UROGENITAL RIDGE  NEPHROGENIC CORD Nephrogenic cord extends from the cervical region to the sacral region of the embryo. At varying stages of development, a number of important structures are formed in relation to the nephrogenic cord on each side: Excretory renal tubules (para-, meso- and metanephric) associated with the development of the kidney. Nephric duct which is formed in relation to the developing excretory tubules. At later stages, this becomes the mesonephric duct. Paramesonephric duct, which is formed lateral to the nephric duct. Gonad (testis or ovary), which develops from the coelomic epithelium lining the medial side of the nephrogenic cord.  CLOACA Part of hindgut caudal to allantois is called cloaca. It is divided by the urorectal septum (in the angle between allantois and cloaca) into dorsal primitive rectum and ventral primitive urogenital sinus. In further development, the primitive urogenital sinus is subdivided into a cranial part, called the vesicourethral canal, and a caudal part, called the definitive urogenital sinus. The openings of the mesonephric ducts lie at the junction of these two subdivisions.  STAGES OF THE KIDNEY FORMATION Nephrogenic cord forms 3 successive kidneys: 1. Pronephros, 2. Mesonephros, 3. Metanephros succeeding each other in time and space such that last to develop is retained as permanent kidney. STAGES OF THE KIDNEY FORMATION STAGES OF THE KIDNEY FORMATION  PRONEPHROS 1. Pronephros: 1st embryonic excretory organ (rudimentary in human) Arises in the cervical region of the embryo during the 3-4th week of development Migrates caudally to connect with the pronephric duct Composed of: pronephric duct and nephric tubules (nephrotome) → temporary excretory function Degenerates with the development of the mesonephros. Pronephric duct - which opens in cloaca persists, which is subsequently annexed by mesonephros and forms the mesonephric duct.  MESONEPHROS 2. Mesonephros: 2nd embryonic excretory organ, developing caudally to the pronephros and degenerating with the development of the metanephros Arises in the 4th week of in the thoracolumbar region  MESONEPHROS 2. Mesonephros: A series of excretory S-shaped, hollow tubules develop in mesonephros, which drain into the mesonephric duct (Wolffian duct); Forms Bowman’s capsule Most of the mesonephric tubules disappear, but some of them take part in forming the duct system of the testis Functions until the end of the 2nd month, then degenerates Caudal end: contributes to male genital system: forms the epididymis, ductus deferens, seminal vesicle, and the ejaculatory duct in male embryos. MESONEPHROS  MESONEPHROS: PRIMITIVE URINARY SYSTEM Small glomerular vessels grow posteriorly off the aorta toward the mesonephric tubules, forming primitive renal corpuscles: Mesonephric tubules grow around the glomerular capillaries, forming Bowman capsules (though these will ultimately regress). Some details of developing pronephros, mesonephros and metanephros  FILTRATION Filtration of blood begins: Blood flows down the aorta  glomerular capillaries  filtered through Bowman capsule  filtrate travels down the mesonephric tubule  mesonephric duct  cloaca  allantois.  METANEPHROS 3. Metanephros: 3 embryonic excretory organ, developing caudally to the mesonephros and rd persisting as the permanent kidney Arises during the 5th week of development Canalization is complete by the 10th week of development. Maturing of the kidneys continues until week 35-36th development. METANEPHROS develops from: outgrowth of the caudal mesonephric duct - ureteric bud condensation of intermediate mesoderm - metanephric blastema. Reciprocal induction - two-way interaction when metanephric mesoderm and metanephric blastema promote each other growth by production of growth factors (GF). Some details of developing pronephros, mesonephros and metanephros  METANEPHROS Metanephric blastema ultimately becomes the cells making up the nephrons Ureteric buds grow toward and invade the metanephric blastema: Elongating stalk of the ureteric bud develops into the ureter. Within the metanephric blastema, the ureteric buds undergo a series of branching to form the: Ureter Renal pelvis Major calyces Minor calyces Collecting tubules DEVELOPMENT OF A NEPHRON IN THE METANEPHROS Development of ureteric bud and metanephric blastema as seen in lateral view of embryo. The inset shows structures derived from the ureteric bud.  DEVELOPMENT OF EXCRETORY SYSTEM Cells of metanephric blastema when come in contact with each collecting tubule, these condens around it to form solid clump of cells called metanephric cap. Each metanephric cap is soon converted into a vesicle called metanephric vesicle. Metanephric vesicle first becomes a pear-shaped vesicle, which soon forms an S-shaped tubule called primitive renal tubule. Proximal end of this S-shaped tubule is narrow and abuts on the collecting tubule. Distal dilated end of this tubule forms Bowman’s capsule. It becomes invaginated by a tuft of capillaries to form renal glomerulus. Glomerular capillaries: develop from the common iliac arteries  DEVELOPMENT OF EXCRETORY SYSTEM Renal glomerulus develops from angioblastic tissue of the nephrogenic cord. Primitive renal tubule eventually forms nephron (excretory unit) consisting of glomerular (Bowman’s) capsule, proximal convoluted tubule, loop of Henle, and distal convoluted tubule. Each distal convoluted tubule joins with the collecting tubule derived from the ureteric bud to form uriniferous tubule. (Note: True waste products from the fetus are removed via the placenta) DEVELOPMENT OF THE KIDNEY AND URETER  URORECTAL SEPTUM a) Separate the cloaca into two distinct parts Anterior portion Becomes urogenital sinus Becomes urinary bladder and urethra Posterior portion Anal canal b) Separate hindgut away from cloaca URORECTAL SEPTUM  SUBDIVISION OF UROGENITAL SINUS Proximal portion of urogenital sinus – vesiculo-urethral part Becomes urinary bladder Middle (pelvic) portion of urogenital sinus Becomes urethra Female → female urethra Male → prostatic urethra, membranous urethra Distal (phallic) portion of urogenital sinus Vaginal vestibule (female) Becomes penile urethra (male)  DEVELOPMENT OF URINARY BLADDER Initially into the base of the urinnary bladder both Wolffian (mesonephric) ducts enter together with both ureteric buds (bases of future ureters) Later they become independent, the ureters move more laterally and proximally, Wolffian ducts dorsally and caudally On the inside of the bladder, there is a small triangular field – future trigonum vesicae.  DEVELOPMENT OF URINARY BLADDER Initially into the base of the urinnary bladder both Wolffian (mesonephric) ducts enter together with both ureteric buds (bases of future ureters) Later they become independent, the ureters move more laterally and proximally, Wolffian ducts dorsally and caudally Specialised transitional epithelium of the bladder develops from endoderm of the urogenital sinus.  RELOCATION OF THE KIDNEY AND CHANGES IN VASCULARIZATION Kidneys are initially located in the pelvic region. As the caudal portion of the body grows downward, the relative location of the kidneys “ascends” into the upper quadrants of the abdomen (failure to ascend results in a pelvic kidney). As the kidneys ascend, the original blood supply degenerates. New vessels (higher up) develop from the aorta and invade the kidneys, becoming the mature renal arteries. If the original vessels fail to regress, they may persist as additional renal arteries or veins. RELOCATION OF THE KIDNEY  CONGENITAL ANOMALIES Agenesis (absence of kidney) (A) – If it is bilateral → incompatible with life – Defect in differentiation of the ureteric bud Hypoplasia of kidney (B) Supernumerary kidney (C) Double kidney (D)  CONGENITAL ANOMALIES Dysplasia of kidney – Aplastic kidney: none parenchyma, small kidney – Cystic kidney: kidney is bigger, many cysts in the parenchyma Positional anomalies of kidney – Pelvic kidney (A) – Crossed ectopia (B): ureteric bud crosses the central plane of the kidney and here induces an origin of a kidney, on the other side the kidney is missing  ADRENAL GLAND ORIGIN Adrenal glands develop from two separate embryological tissues: medulla is derived from neural crest cells originating in proximity to the dorsal aorta (ganglion in origin), cortex develops from the intermediate mesoderm.  OVERVIEW OF TYPICAL SEX DEVELOPMENT o Chromosomal sex → determines gonadal sex → determines phenotypic sex o Up until 6 weeks of gestation, sex development is identical and nonbinary; Developing structures include: Nonbinary, bipotent, undifferentiated gonads Mesonephric ducts (also known as Wolffian ducts; also part of the primitive urinary system) Paramesonephric ducts (also known as Müllerian ducts) Urogenital sinus Genital tubercle, genital swellings, and genital folds  INDIFFERENT STAGE Gonads develop from three sources: 1. Intermediate mesoderm 2. Celomic epithelium covering the intermediate mesoderm 3. Primordial germ cells Gonads develop in the intermediate mesoderm – medial to middle part of mesonephros. The first indication of development of primitive gonad is seen at about 4th week. An elongated elevation called genital ridge appears on medial side of mesonephric ridge. Genital ridge is formed by condensation of intermediate mesoderm and proliferation of overlying celomic epithelium  PRIMORDIAL GERM CELLS Yolk sac contains the primordial germ cells (PGCs), which will: Migrate through the vitelline duct; Invade the urogenital ridge PGCs will give rise to the gametes (sperm and oocyte) A) Primordial germ cells developing in the wall of yolk sac close to the attachment of allantois. B) Migration of primordial germ cells along the wall of hindgut and its dorsal mesentery into the developing gonad.  GENETIC INFLUENCE Genes present at fertilization will determine how the developing bipotent gonads differentiate (e.g., into a testis or an ovary). Further differentiation of the gonads is dependent on the presence or absence of the SRY gene on the Y chromosome SRY gene encodes for a testis determining factor (TDF)  stimulates differentiation of the testes in male individuals. Mullerian inhibitory factor (MIF), produced by Sertoli cells in testes, suppresses the differentiation of the paramesonephric ducts (female). o Y-chromosome  SRY-gene  testis o No Y-chromosome and presence of WNT4 gene  ovary  HORMONAL STIMULATION Developing gonads will then secrete hormones. Testosterone (produced by Leydig cells) drives the differentiation of the mesonephric ducts into male internal organs and dihydrotestosterone drives the differentiation of male external genitalia. In female individuals, the absence of MIF allows differentiation of the paramesonephric ducts into the female internal organs, and estrogen drives the differentiation of female external genitalia. Absence of testosterone prevents the differentiation of the mesonephric ducts in female individuals.  Overview of ductal sex differentiation Male Embryonic structure General description individuals (starting Female individuals the 7th week) (starting the 8th week) Develop from mesoderm until the end of the 8th week Fallopian tubes Paramesonephric Precursors to female internal sex Degenerate into appendix Uterus ducts (Mullerian ducts) organs testis Proximal vagina Differentiation is driven by estrogens and suppressed by MIF. Develop from mesoderm until Seminal vesicles the 6th week Ejaculatory duct Precursors to male internal sex organs Degenerate into vestigial Mesonephric Epididymis (also (except prostate) remnants paradidymis) ducts (Wolffian ducts) Differentiation is driven Ductus deferens (appendix vesiculosa and by testosterone. Gartner duct) Function as a part of the *Mnemonic: SEED primitive kidney during the 1st trimester DEVELOPMENT OF REPRODUCTIVE SYSTEMS DEVELOPMENT OF REPRODUCTIVE SYSTEMS  EXTERNAL GENITALIA DIFFERENTIATION Description: development of the embryonic ducts into the external genitalia Timeline: starts in week 9 Mechanism: primarily driven by the presence or absence of estradiol and dihydrotestosterone Male: testosterone → dihydrotestosterone (via 5α-reductase) → differentiation of embryonic structures into male external genitalia, bulbourethral glands, and prostate gland Female: estradiol and absence of DHT → differentiation of embryonic structures into female external genitalia.  Overview of external genitalia and urogenital differentiation Embryonic Notable characteristics Male individuals Female individuals structure Glans penis First forms primordial Glans clitoris Genital tubercle phallus Corpus cavernosum Vestibular bulbs Corpus spongiosum Greater vestibula glands (Bartholin) Bulbourethral Develops from cloaca Urethral and paraurethral during the 4–6th weeks glands (Cowper) glands (Skene) Urogenital sinus Prostate gland Precursor to bladder Distal vagina and urethra (both sexes) Bladder Vestibule Urethra Bladder Urethra Ventral penile shaft Urogenital folds N/A Labia minora Penile urethra Labioscrotal N/A Scrotum Labia majora swelling DEVELOPMENT OF EXTERNAL GENITALIA A and B at different stage. C and D in female. E and F in male. (A) Cloacal membrane; (B) Cloacal membrane divides into urogenital membrane and anal membrane; (C) Right and left genital swellings, and a median genital tubercle appear; (D) Urogenital membrane breaks down. Its edges form the primitive urethral folds; (E) Genital tubercle becomes the glans penis.primitive urethral folds and groove are seen; (F) Formation of definitive urethral groove and urethral folds are formed. The genital swellings fuse to form the scrotum  DESCENT OF GONADS Description Migration of the testes caudally from their initial retroperitoneal location through the inguinal ring into the scrotum Migration of the ovaries caudally to the pelvic rim Timeline: complete by week 33 *The descent of the gonads, which is much more prominent in male individuals, is facilitated by the gubernaculum, which promotes the descent of the testes. SUMMARY SUMMARY MCQ for self-control https://forms.gle/dPWvXfEYW2k6HTLAA REFERENCES