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Urogenital system 陳建榮 http://web.nchu.edu.tw/pweb/users/chenjr/ Development of Urogenital System Adrenal Glands Kidneys The development of the kidneys from the pronephros to their ascent to the level of L1. Reproductive System The development of male and female genitalia from the partitioning of the cloaca to the final differentiated state. Embryology of the urogenital system -Urinary system -Genital system Urogenital ridge (intermediate mesoderm) along the posterior abdominal wall -- urinary system nephrogenic cord生腎索 -- genital system gonadal ridge生殖脊 Kidney develops first (functional; reproductive later) Urinary system Genital system Normal Development of the Adrenal Glands Formation of the adrenal cortex The adrenal glands is derived from the intermediate mesoderm. The adrenal glands have two developmentally distinct parts: the medulla and the cortex. Formation of the adrenal medulla Development of zones of adrenal gland 球小帶 (Aldosterone ) 束狀帶 (Glucocorticoids ) 網狀帶 (DHEA) 6th weeks Normal Development of the Adrenal Glands Formation of the adrenal cortex Formation of the adrenal medulla Neural crest cells migrate into the center of this aggregate to develop the adrenal medulla. The cells differentiate into sympathetic nerve cells and show evidence of catecholamine production in 10th week of fetal life. Development of zones of adrenal gland Normal Development of the Adrenal Glands Formation of the adrenal cortex Formation of the adrenal medulla Development of zones of adrenal gland -During fetal period -zona glomerulus球小帶 -zona fasciculata束狀帶 -3 years old -zona reticularis網狀帶forms -The fetal adrenal glands are larger than the fetal kidney at four months. Even at birth they are relatively quite large (about 20 times their relative size in the adult). -After birth, the fetal cortex rapidly undergoes regression. 2 1 3 Congenital adrenal hyperplasia (CAH) 先天性腎上腺增生症 Normal Development of the Urinary System Development of kidney Early kidney development (pronephros) Development of mesonephros Development of metanephros Ascent of the kidneys Development of the Urinary Bladder Normal Development of the Kidneys Pronephros: 原腎(4th week, nonfunctional) -mesenchymal cell aggregates in neck region of embryo, and soon transformed into ligament -pronephros attached to pronephric ducts原腎管 -promesonephric ducts used in next stage of kidney development, these ducts end in the cloacal region caudal to the mesenchymal cell aggregates of the pronephros. Mesonephros: Metanephros: Normal Development of the Kidneys Pronephros: (4th week, nonfunctional) Mesonephros: 中腎(functional) -mesonephros begins development late in 4th week lie caudal to pronephros -mesonephros consists of glomeruli and mesonephric tubules中腎小管 which open into mesonephric duct, a continuation of the pronephric duct mesonephric duct opens into cloaca -mesonephros proper degenerates but tubules and ducts have derivatives in adult males (tubules form ductuli efferentes輸出小管 and ducts form a number of reproductive structures to be discussed later). Metanephros: Development of the Metanephros後腎: -The ureteric bud forms from an outgrowth of the mesonephric duct near the cloaca. The ureter, renal pelvis, major and minor calyces, collecting ducts and collecting tubules are all formed from the ureteric bud. -The metanephric mesenchyme forms from the caudal portion of the intermediate mass, and it surrounds the end of the ureteric bud. -As the kidney grows the ureteric bud forms finger-like projections. -The first 4 generations of the projections form the major calyx, the next 2 generations form the minor calyces, and the remaining projections form the straight and arched collecting tubules. 腎盂 Normal development of Nephrons -The arched collecting tubules induce growth of the surrounding mesenchyme, which forms a tubule in the metanephric mass後腎原基 of mesoderm. -These tubules form the parts of the nephron: glomerulus, Bowman's capsule, convoluted tubule, loop of Henle. -Formation of the nephrons of the permanent kidney begins at 8th week. -The metanephric vesicles elongate to form tubules which directly contact the arched collecting tubules. -The metanephric tubules are lobulated and remain this way until after birth. Normal Development of the Urinary System Development of kidney Early kidney development (pronephros) Development of mesonephros Development of metanephros Ascent of the kidneys Development of the Urinary Bladder Ascent of the kidneys -During the 5th and 6th weeks of development, the mature kidneys lie in the pelvis with their hila pointed anteriorly. -As the pelvis and abdomen grow, the kidneys slowly move upward. -By the 7th week, the hilum points medially and the kidneys are located in the abdomen. -As the embryo continues to grow in a caudal direction, the kidneys come to lie in a retroperitoneal position at the level of L1 by the 9th week of development. Clinical problems Accessory renal arteries Renal agenesis Bilateral renal agenesis Malrotated kidney Ectopic kidney Duplication of urinary tract Ectopic ureter Duplication of urinary tract Horseshoe kidney Development of Urinary Bladder -Cloaca (uro-rectal septum尿生殖隔) -urogenital sinus泌尿生殖竇 -Anorectal canal肛門生殖管 -The uro-genital sinus may be divided into three component parts. -The cranial portion which is continuous with the allantois and forms the bladder proper. -The pelvic part of the sinus forms the prostatic urethra and epithelium as well as the membranous urethra and bulbo urethral glands in the male and the membranous urethra and part of the vagina in females. -The caudal portion, or definitive uro-genital sinus, forms the penile urethra in males and the vestibule in females. -The trigone portion is formed by the caudal ends of the mesonephric ducts. -The mesonephric ducts begin to become incorporated into the wall of the bladder dragging the ureters along with them. -The mesonephric ducts enter the prostatic part of the urethra. -In females, the ducts then degenerate. In males, the ducts form the origin of the ejaculatory ducts. -The bladder is initially continuous with the allantois. -Over time, the allantois degenerates to form a cord-like structure, the urachus. -The urachus goes from the umbilicus to the apex of the bladder and forms the median umbilical ligament which can be seen in adults. Clinical problems Urachal anomalies Extrophy of bladder膀胱外翻 Normal development of Reproductive System Bipotential Phase Early Development (pre-differentiation) Partitioning of the Cloaca Male Development Development of the Testes Development of External Genitalia Female Development Development of the Ovaries Development of the Vagina Development of External Genitalia Summary of Derivatives of Embryonic Structures • The chromosomal & genetic sex of an embryo is determined at fertilization by the kind of sperm that fertilizes the ovum. • Male & female characteristics begin to develop at the 7th week. • The early genital system in the two sexes are similar the initial period of genital development is called indifferent stage of sexual development. Early Genital System Development -Early in the 4th week, the primordial germ cells may be seen in the endoderm around the allantois. -These germ cells migrate under the coelomic epithelium, around the gut to the dorsal mesentery. Regulation of germ cell migration 有無不孕症 可能娘胎就決定 2015-06-05 02:48:35 聯合報 記者陳皓嬿、黃筱雅、陳雨鑫/綜 合報導 Indifferent Gonads • It is the Initial stage in 5th week thickened area of mesothelium develops on the medial side of the mesonephros proliferation form a bulge on the medial side (Gonadal (genital) ridge). • Primary sex cord初級性索 ( fingerlike epithelial cords) grow into the underlying mesenchyme. • The indifferent gonad consists of an external cortex and internal medulla • In femalethe cortex of indifferent gonads form the ovary & the medulla regress. • In male the medulla form the testis & cortex regress except for vestigial remnants. (SRY) Development of the Gonads (Testes & Ovary) The gonads (testes & ovary) are derived from 3 sources: 1) The mesodermal epithelium lining the posterior abdominal wall. 2) The underlying mesenchyme. 3) The primordial germ cells. Nephorgenic cord: -Mesonephric duct -epidydimis; ductus deferen -Paramesonephric duct -uterine tube; uterus Partitioning of Cloaca Internal structure -The caudal end of the hindgut is lined with endoderm and is known as the cloaca泄殖腔. -At the end of the cloaca, the there is a cloacal membrane泄殖膜 which separates the endoderm from the surface ectoderm. -The uro-rectal septum泌尿直腸膈 migrates caudally to divide the cloaca into dorsal and ventral aspects. -On the ventral side, attaching to the allantois is the primitive urogenital sinus泌尿生殖竇. The primitive ano-rectal canal肛門直腸管 lies dorsally. -As the division is completed, at 7th weeks, the cloacal membrane is also divided into uro-genital membrane泌尿生殖膜and anal membrane肛門直腸膜. Urogenital sinus Ano-rectal canal Partitioning of Cloaca External structure -As the urogenital septum is migrating caudally, the intermediate masses are also proliferating. -These mesodermal masses form a genital tubercle生殖結節 at the ventral tip of the cloacal membrane. -Labioscrotal swellings陰唇陰囊隆起 and urogenital folds泌尿生 殖褶develop shortly thereafter on each side of the cloacal membrane. -When the urogenital septum reaches the cloacal membrane, dividing it into anal membrane and urogenital membrane. -The embryo is still in its bipotential phase at this point and has the potential to develop either male or female external genitalia. Normal development of Reproductive System Bipotential Phase Early Development (pre-differentiation) Partitioning of the Cloaca Male Development Development of the Testes Development of External Genitalia Female Development Development of the Ovaries Development of the Vagina Development of External Genitalia Summary of Derivatives of Embryonic Structures Development of Testes -Embryos which contain the Y chromosome have a specific gene known as SRY(sex-determining region Y gene, testis-determining factor, TDF ). -SRY is expressed in the mesenchyme and cause a cascade of events leading to the formation of internal male organs. -The first step in the development of the testes is the formation of the tunica albuginea白膜, a layer of fibrous connective tissue which separates the sex cords (seminiferous cords精索) from the surface epithelium. -Within the tunica albuginea, the seminiferous cords are separated from one another by mesenchyme. -The mesenchyme Leydig cells. 7th week -Leydig cells produce testosterone to promot the mesonephric duct. -The renal corpuscle is degenerating, which allows the tubules of the mesonephros to hook up to the rete testis睪丸網 ductuli efferentes輸出管. -These tubules are continuous with the mesonephric duct, which is now known as the epididymis副睪. -The seminiferous cords are solid (i.e. no lumen) until puberty but they are made up of a large number of Sertoli cells, a highly proliferative cell which secretes antimullerian hormone (AMH). -AMH inhibits the paramesonephric ducts副中腎管 which then degenerate around the 9th week of development. -The seminiferous cords remain solid until puberty at which time a lumen develops and they become the seminiferous tubules. Development of Genital Ducts • Both male & female embryos have 2 pairs of genital ducts: 1) The mesonephric (wolffian) ducts中腎管 important in the development of the male reproductive system. 2) The paramesonephric ( mullerian) ducts副中腎 管 important in female reproductive system. • In indifferent stage of the genital system the male & female genital ducts are present. The Mesonephric ducts中腎管 • These ducts drain urine from the mesonephric kidney. • Also, under the influence of testosterone, the proximal part of each mesonephric duct become convoluted to form the epididymis. • Müllerian inhibiting substance (AMH/MIS) causes the paramesonephric ducts to disappear by epithelial mesenchymal transformed. • The remainder of mesonephric duct forms the ductus deferens輸精管 & ejaculatory duct射精管. • In Female the mesonephric ducts are completely disappear, only a few non-functional remnant persist. • Prostate前列腺: multiple endodermal outgrowths arise from the prostatic part of the urethra & grow into the surrounding mesenchyme. • Bulbourethral glands尿道球腺: pea-sized structures develop from paired outgrowths form the spongy part of the urethra. The secretions of these glands contribute to the semen. Development of Male External Genitalia -Testosterone male external genitalia -Genital tubercle生殖結節 penis -Urogenital folds泌尿生殖褶 urethral groove尿道溝. -The urogenital folds fuse together on the ventral side of the developing penis, enclosing what will now become the spongy urethra. -The foreskin is formed in the 12th week of development. -A septum of ectoderm moves inward around the edges of the penis and then breaks down, leaving a thin layer of skin surrounding the penis. -During this time, the penis is also developing its corpus cavernosa and spongiosa from proliferating mesenchyme within the genital tubercle. Clinical problems Glandular hypospadia Normal development of Reproductive System Bipotential Phase Early Development (pre-differentiation) Partitioning of the Cloaca Male Development Development of the Testes Development of External Genitalia Female Development Development of the Ovaries Development of the Vagina Development of External Genitalia Summary of Derivatives of Embryonic Structures Development of the Ovaries -In the absence of SRY/TDF, the primary sex cords are not nearly so welldeveloped as in the male embryo. -The cortex is much better developed and it forms secondary sex cords that extend from the surface epithelium to the mesenchyme. Development of the Vagina -The paramesonephric ducts develop in the female because of a lack of antimullerian hormone (AMH). -These paramesonephric ducts form the majority of the female reproductive tract. -The fallopian tubes develop from the upper unfused portions of the ducts while the lower fused portion of the ducts forms a uterovaginal primordium which gives rise to the uterus and vagina. -The sinovaginal bulbs竇陰道球 form when the uterovaginal primordium子宮陰道原基 contacts the urogenital sinus. 子宮陰道原基 竇陰道球 Clinical problems Clinical problems Pseudohermaphrodite假性陰陽人 caused by CAH Development of Female External Genitalia Clinical problems Congenital anomalies of hymen Vagina ends blindly Androgen insensitivity syndrome Pseudohermaphrodite假性陰陽人 caused by androgen insensitivity Descent of gonads Descent of the testis -Gubernaculum引帶 -Proper lig. of testis睪丸固有韌帶 -Lig. of tail of epididymis副睪尾韌帶 -The testis descends through the inguinal canal into the scrotum at the time of birth. -The testis is then covered by a layer of peritoneum, the visceral layer of the tunica vaginalis -The remainder of the peritoneal sac forms the parietal layer of the tunica vaginalis鞘膜. -The canal connecting the lumen of the vaginal process鞘突 with the peritoneal cavity is obliterated at birth or shortly thereafter. Descent of the ovary -The ovaries also descend to their position in the true pelvis. -Gubernaculum -ovarian ligament 卵巢固有韌帶 -round ligament of the uterus子宮圓韌帶 (extending to the labia majora). Clinical problems Possible site of cryptorchid and ectopic testies Failure of closure of the processus vaginalis Reproductive System Bipotential Phase Early Development (pre-differentiation) Partitioning of the Cloaca Male Development Development of the Testes Development of External Genitalia Female Development Development of the Ovaries Development of the Vagina Development of External Genitalia Summary of Derivatives of Embryonic Structures Male Female Embryonic Structure Indifferent gonad Cortex Male Female ovary Adult testis Equivalents of Embryonic Structures seminiferous tubules ovarian follicles Medulla rete testis rete ovarii Gubernaculum gubernaculum testis ovarian and round ligament of uterus Mesonephric tubules ductuli efferentes epoophoron, paroophoron Mesonephric Duct appendix of epididymus, duct of epididymus, ductus deferens, ureter, calices and collecting tubules, ejaculatory duct and seminal vesicles appendix vesiculosa, duct of epoophoron, duct of Gartner, ureter, pelvis, calices and collecting tubules Paramesonephric Duct appendix of testis hydatid of Morgagni, uterine tube, uterus Urogenital Sinus urinary bladder, urethra, urinary bladder, urethra, prostatic utricle, prostate gland vagina, urethral, paraurethral and bulbourethral glands and greater vestibular glands Sinus tubercle seminal colliculus hymen Phallus penis clitoris Urogenital folds ventral aspect of penis labia minora Labioscrotal swellings Scrotum labia majora