Organogenesis 3: Gut and Urogenital System
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Describe the development of the hindgut
- The hindgut gives rise to the distal third of the transverse colon, the descending colon, the sigmoid, the rectum, and the upper part of the anal canal. The endoderm of the hindgut also forms the internal lining of the bladder and urethra.
- The terminal portion of the hindgut enters into the posterior region of the cloaca, the primitive anorectal canal;
- - the allantois enters into the anterior portion, the primitive urogenital sinus.
- - A layer of mesoderm, the urorectal septum, separates the region between the allantois and hindgut.
- At the end of the seventh week, the cloacal membrane ruptures, creating the anal opening for the hindgut and a ventral/anterior opening for the urogenital sinus.
- - Between the two, the tip of the urorectal septum forms the perineal body (a.k.a perineum).
Describe the mesodermal fates. Which results in the kidneys and gonads?
Describe the contribution of the pronephros, mesonephros and metanephros to the permanent kidney and urinary tract.
- Pronephros: At the beginning of the fourth week, a temporary/transient/vestigial kidney system is set up
- - By the end of the fourth week, all indications of the pronephric system have disappeared.
- Mesonephros: another temporary/transient/vestigial kidney system
- - First excretory tubules appear in the early in the fourth week of development, during regression of the pronephric system
- - In the male, a few of the caudal tubules of the mesonephric duct persist and participate in formation of the genital system, but they disappear in the female.
- - ureteric bud (future adult renal pelvis) forms from branch of the mesonephric duct. The bud dilates, forming the primitive renal pelvis, and splits into cranial and caudal portions, the future major calyces
- Metanephros: permanent kidney which appears in the fifth week.
- - Its excretory units develop from metanephric mesoderm in the same manner as in the mesonephric system. The development of the duct system differs from that of the other kidney systems
How does the permanent kidney system develop?
- Collecting ducts of the permanent kidney develop from the ureteric bud (a.k.a. Metanephric diverticulum).
- The bud dilates, forming the primitive renal pelvis, and splits into cranial and caudal portions, the future major calyces.
- - Each calyx forms two new buds while penetrating the metanephric tissue. These buds continue to subdivide until heaps of tubules have formed.
- - The ureteric bud gives rise to the ureter, the renal pelvis, the major and minor calyces, and approximately 1 to 3 million collecting tubules.
- At the end of these mesonephric tubules, the metanephric tissue forms the excretory units; i.e. the proximal convoluted tubule, loop of Henle, and distal convoluted tubule (everything blue in the pic below and NOT GLOMERULI)
- - a processes regulated by gene expression and chemical regulators
Describe how the kidneys reach their position developmentally
- The kidney, initially in the pelvic region, later shifts to a more cranial position in the abdomen.
- This ascent of the kidney is caused by diminution of body curvature and by growth of the body in the lumbar and sacral regions
- - (in other words, it's not so much that the ureters elongate. Rather the body elongates around these structures).
- Note the change in position between the mesonephric and metanephric systems. The mesonephric system degenerates almost entirely, and only a few remnants persist in close contact with the gonad.
- - In both male and female embryos, the gonads descend from their original level to a much lower position
- The kidneys become vascularised via the dorsal aorta
Comment on how the foetus deals with urine
- Urine production begins about week 12.
- It passes into amniotic fluid
- Baby swallows fluid
- Placenta serves excretion of waste products
Describe how some kidney abnormalities result from errors in development.
- Horseshoe kidney: Sometimes, the kidneys are pushed so close together during their passage through the arterial fork, that the lower poles fuse, forming a horseshoe kidney
- - The horseshoe kidney is usually at the level of the lower lumbar vertebrae, since its ascent is prevented by the root of the inferior mesenteric artery. The ureters arise from the anterior surface of the kidney and pass ventral to the isthmus in a caudal direction.
- - Horseshoe kidney is found in 1/600 people.
- Pelvic kidney: During their ascent, the kidneys pass through the arterial fork formed by the umbilical arteries, but occasionally, one of them fails to do so. Remaining in the pelvis close to the common iliac artery
- Ectopic ureter: In rare cases, one ureter opens into the bladder, and the other is ectopic, entering the vagina, urethra, or vestibule. This abnormality results from development of two ureteric buds.
- - One of the buds usually has a normal position, whereas the abnormal bud moves down together with the mesonephric duct (which descends with the gonads; see later flashcards).
- - Thus, it has a low, abnormal entrance in the bladder, urethra, vagina, or epididymal region.
- Polycystic kidney: In congenital polycystic kidney disease, numerous cysts form.
- - It's usually genetic, and comes in 2 forms; autosomal recessive or autosomal dominant disorders (or may be caused by other factors).
- - The autosomal dominant disease is more common but less progressive (i.e. it usually do not cause renal failure until adulthood) compared to the autosomal recessive disease.
Define the role of the Y chromosome in determining the sex of the gonads.
- Sex differentiation is a complex process that involves many genes, including some that are autosomal. But the key to sexual dimorphism is the Y chromosome, which contains the testis-determining gene called the SRY (sex-determining region on Y) gene.
- The SRY protein is the testis-determining factor; under its influence, male development occurs; in its absence, female development is established
- - Also required for male development is the product of autosomal gene SOX9, which allows downstream production of "anti-Mullerian hormone AMH"; think that the mullerian duct (primitive female tract) regresses with AMH → male development.
- In essence, a male vs. female fate is based on genetic factors, which determine chemical exposures which determine male vs. female tissue differentiation of the gonads and mullerian/wolffian ducts
Describe the fate of the müllerian ducts in females
- Wolffian or mesonephric duct completely regresses in the female
- Mullerian or Paramesonephric duct give rise to the;
- - Utererine tubes
- - Upper vaginal canal
- - Uterus; fusion of the paired paramesonephric/Mullerian ducts
Describe the fate of the wolffian ducts in males
- Mullerian Duct pretty much fully regresses
- - aided by +MIS (made by the Sertoli cells)
- Wolffian or mesonephric duct form (everything blue in the picture above);
- - Epididymis,
- - Vas deferens
- - Seminal vesicle
- - Ejaculatory duct
Describe the differences in the differentiation of male/female external genitalia
- The male and female external genitalia develop from a single bipotential precursor.
- Male differentiation: involves conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase. DHT mediates prostatic development and the repression of vaginal development.
- - At 10 weeks, masculinisation of the external genital organs begins in the 10 week old fetus by lengthening of the distance between the anus and urethra.
- - Shaft of the penis: formed by fusion of the urethral folds to enclose the urethral tube
- - Scrotum: The genital swellings become the scrotal swellings, and fuse in the midline, forming the scrotum.
- - The knob: The genital tubercle expand to form the glans penis
- Female differentiation: is a process independent of the ovaries; i.e. if removed, these changes still occur, indicating their independence of ovarian endocrine activity.
- - Labia minora/majora: The urethral folds and genital swellings remain separate, forming the labia minora and majora
- - Clitoris: The genital tubercle forms the clitoris.
- - External genitalia; female: independence of ovary
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