Adam Irsyaddyra 0910711001 PDB

ANATOMY 4 : GENITALIA DEVELOPMENT

1. Chromosomal and genetic sex depends on whether an X-bearing sperm or a Y-bearing sperm
fertilizes the X-bearing oocyte. Before the seventh week, the gonads of the two sexes are identical in appearance and are called indifferent gonads. What is the sex determining factor? Explain how could it determine the type of sexual differentiation Development of the male phenotype requires a Y chromosome. The SRY gene for a testis-determining factor (TDF) has been localized in the sex-determining, short arm region of the Y chromosome. It is the TDF regulated by the Y chromosome that determines testicular differentiation. Under the influence of this organizing factor, the gonadal cords differentiate into seminiferous cords (primordia of seminiferous tubules). Expression of the Sox9 and Fgf9 genes is involved in the formation of the seminiferous cords. The absence of a Y chromosome results in the formation of an ovary. Two X chromosomes are required for the development of the female phenotype. A number of genes and regions of the X chromosome have special roles in sex determination. Consequently, the type of sex chromosome complex established at fertilization determines the type of gonad that differentiates from the indifferent gonad. The type of gonads present then determines the type of sexual differentiation that occurs in the genital ducts and external genitalia. Testosterone, produced by the fetal testes, dihydrotestosterone, a metabolite of testosterone, and the antimllerian hormone (AMH), determines normal male sexual differentiation. Primary female sexual differentiation in the fetus does not depend on hormones; it occurs even if the ovaries are absent and apparently is not under hormonal influence. (The Developing Human 8th) 2. Describe the development of ovary o Pada mudigah wanita yg mempunyai unsur kromosom seks XX dan tdk mempunyai kromosom Y, korda kelamin primitif terputus-putus menjadi kelompok2 sel yg tdk teratur bentuknya. Kelompok2 sel ini,yg mengandung gugus2 sel benih primordial, terletak di bagian medulla ovarium. Kemudian, kelompk2 ini menghilang dan digantikan oleh stroma vaskuler yg membentuk medulla ovarium. o Epitel permukaan gonad wanita, tdk spt pd pria, terus menerus berproliferasi. Dlm minggu ke 7, epitel ini membentuk korda generasi ke 2, korda korteks, yg menembus mesenkim di bawahnya, tetapi ttp dekat dg permukaan. Dlm bulan ke 4, korda ini terpecah menjadi kelompok2 sel tersendiri, yg masing2 mengelilingi satu atau lebih sel benih primitif. Sel2 benih berkembang menjadi oogonia, sedangkan sel epitel di sekitarnya, yg berasal dr epitel permukaan, membentuk sel folikuler.

(Langman) 3. During the fifth and sixth weeks, the genital system is in an indifferent state, and two pairs of genital ducts are present. The mesonephric ducts (Wolffian ducts) play an important part in the development of the male reproductive system and the paramesonephric ducts (Mullerian ducts) have a leading role in the development of the female reproductive system.

Describe the molecular regulation of genital duct development SRY is the master gene for testes development and appears to act directly on the gonadal ridge and indirectly on the mesonephric ducts. Thus, it induces the testes to secrete a chemotactic factor that causes tubules from the mesonephric duct to penetrate the gonadal ridge and stimulate further testicular development. In fact, without penetration by these tubules, differentiation of the testes fails. SRY also upregulates steroidogenesis factor 1 (SF1), which acts through another transcription factor, SOX9, to induce differentiation of Sertoli and Leydig cells. Sertoli cells then produce mullerian inhibiting substance (MIS, also called antimullerian hormone, AMH) that causes regression of the paramesonephric (mullerian) ducts. Leydig cells produce testosterone, which enters cells of target tissues where it may remain or be converted to dihydrotestosterone by a 5 reductase enzyme. Testosterone and dihydrotestosterone bind to a specific high-affinity intracellular receptor protein, and ultimately this hormone receptor complex binds to DNA to regulate transcription of tissue-specific genes and their protein products. Testosterone receptor complexes mediate virilization of the mesonephric ducts, whereas dihydrotestosterone receptor complexes modulate differentiation of the male external genitalia. Sexual differentation in females was once thought to be a default mechanism that occurred in the absence of a Y chromosome, but it now appears that there are specific genes that induce ovarian development. For example, DAX1, a member of the nuclear hormone receptor family, is located on the short arm of the X chromosome and acts by downregulating SF1 activity, thereby preventing differentiation of Sertoli and Leydig cells. The secreted growth factor WNT4 also contributes to ovarian differentiation, and its early expression in the gonadal ridge is maintained in females but downregulated in males. In the absence of MIS production by Sertoli cells, the paramesonephric (mullerian) ducts are stimulated by estrogens to form the uterine tubes, uterus, cervix, and upper vagina. Estrogens also act on the external genitalia at the indifferent stage to form the labia majora, labia minora, clitoris, and lower vagina. (Langman 8th)

4. Masculinization of the indifferent external genitalia is induced by testosterone which is produced

by interstitial cells of fetal testes. Could you explain about the development of male external genetalia ? Perkembangan genitalia eksterna pria berada di bwh pngaruh hormon androge yg disekresi oleh testis janin dan ditandai oleh cepat memanjangnya tuberkulum genitalia yg kini dinamakan phallus (penis). Bersama dg pemanjangan ini, phallus menarik lipatan uretra ke dpn sehingga membentuk dinding lateral sulkus uretra. Sulkus ini terbentang sepanjang permukaan kaudal penis ttp tdk mencapai bagian plg distal, yg dikenal sbg glans. Lapisan epitel yg melapisi sulkus ini berasal dari endoderm dan membentuk lempeng uretra. Pada akhir bulan ke 3, kedua lipatan uretra menutup di bagian atas lempeng uretra, shg membentuk uretra pasrs kavernosa. Saluran ini tdk berjalan hingga ujung penis. Bagian uretra yg plg distal ini dibentuk pd bln ke 4 ketika sel2 ektoderm dr ujung glans menembus masuk ke dlm membentuk sebuah korda epitel yg pendek. Korda ini kemudian memperoleh rongga, shg membentuk orifisium uretra eksternum. Tonjol2 kelamin pd pria yg dikenal sbg tonjol skrotum mula2 terletak di daerah inguinal. Pada perkembangan selanjutnya, tonjol ini bergerak ke kaudal, dan tiap2 tonjolan lalu membentuk setengah skrotum. Kedua belahan skrotum dipisahkan satu sama lain oleh sekat skrotum.

(Langman)

5. Errors in sex determination and differentiation result in various degrees of intermediate sex
intersexuality or hermaphroditism. Intersex implies a discrepancy between the morphology of the gonads (testes/ovaries) and the appearance of the external genitalia. What is male pseudohermaphroditism? Pd pseudohermafrodit, genotip jenis kelamin tertutup oleh gambaran fenotip yg sgt mirip dg jenis kelamin lawannya. Pseudohermafrodit pria mempunyai komplemen kromosom 46,XY dan sel2nya biasanya berkromatin negatif. Kurangnya produksi hormon androgen dan SPM merupakan penyebab keadaan ini. Ciri2 genitalia interna dan eksterna dpt sangat beraneka ragamm tergantung pada derajat perkembangan genitalia eksterna dan adanya unsur2 paramesonefros. (Langman)

ANATOMY 5 : HISTOLOGICAL FEATURE OF REPRODUCTIVE SYSTEM

1. Describe the histological feature of ovary at puberty At puberty the ovaries contain about 300,000 oocytes. Because generally only one oocyte resumes meiosis with ovulation during each menstrual cycle (average duration, 28 days) and the reproductive life of a woman lasts about 3040 years, only about 450 oocytes are liberated from ovaries by ovulation. All others degenerate through atresia. The body of uterus consists of a firm outer coat of muscle (myometrium) and an inner lining of vascular, glandular material (endometrium). The endometrium thickens during the menstrual cycle to allow implantation of a fertilized egg. Pregnancy occurs when the fertilized egg implants successfully into the endometrial lining. If fertilization does not occur, the endometrium sloughs off and is expelled as menstrual flow. This cyclic process the menstrual cycle results from the interaction between the female reproductive organs and the endocrine system. Describe differences of endometrium lining uterine cavity according menstrual cycle phase During most of the proliferative phase the functional layer is still relatively thin, the stroma is more cellular and the glands (G) are relatively straight, narrow, and empty. (Junqueira 12th) Pada fase proliferasi, endometrium ditutupi epitel selapis silindris. Kelenjar yg dibentuk oleh sel epitel selapis silindris berbentuk tabung lurus dengan lumen sempit. Sel2 ini secara berangsur mengumpulkan lbh byk sisterna retikulum endoplasma kasar, dan kompleks golgi bertambah besar sebagai persiapan untuk aktivitas sekresi. Pada akhir fase proliferasi, tebal endometrium mencapai 2-3 mm. (Junqueira 10th) In the secretory phase the functional layer is less heavily cellular and perhaps four times thicker than the basal layer. The tubular glands have wider lumens containing secretory product and coil tightly up through the stroma, giving a zig-zag or folded appearance histologically. Superficially in the functional layer, lacunae (La) are widespread and filled with blood. (Jun 12th). Pada fase sekresi/luteal, sel2 epitel mulai menimbun glikogen d bwh intinya. Kemudian,jmlh glikogennya berkurang, dan produk sekresi glikoprotein melebarkan lumen kelenjar2 tsb. Satu ciri penting fase ini adlh kelenjar2 mjd dgt berkelok2. Pada fase ini,endometrium mencapai tebal maksimumnya (5 mm). (Jun 10th) The short premenstrual phase begins with constriction of the spiral arteries, which produces hypoxia that causes swelling and dissolution of the glands (G). The stroma of the peripheral functionalis is more compact and that near the basal layer typically appears more sponge-like during this time of blood stasis, apoptosis and breakdown of the stromal matrix. (Jun 12th). Fifteen to twenty-five lobes of glandular tissue containing mammary alveoli synthesize and secrete the milk in the mammary glands, a process known as lactation. Are there any differences of histological appearance of mammary gland between active phase and lactation? Describe it, please ! Alveoli adlh struktur bulat yg terdiri atas kumpulan sel epitel yg menjadi struktur pensekresi-susu yg aktif selama masa laktasi. Jumlah vakuol sekresi dan tetes lemak sangat bertambah selama laktasi. Jumlah jaringan ikat dan jaringan lemak, dibandingkan parenkim, berkurang selama laktasi. Selama laktasi, susu diproduksi oleh sel2 epitel alveoli dan mengumpul di dlm lumennya dan d dlm duktus laktiferus. Sel2 sekretoris mengecil dan berbentuk kuboid rendah, serta sitoplasmanya engandung tetesan bulat dg berbagai ukuran, yg terutama mengandung trigilserida netral. (Jun 10th)

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3. Mammary glands are an accessory reproductive gland within breasts tissue to produce milk.

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Each testis is composed of an exocrine part and an endocrine part. What is the meaning of that statement? The seminiferous tubules are the exocrine portion of the testis. These tubules are lined by a stratified epithelium that consists of : Could you draw the histological appearance of seminiferous tubule? Tubulus seminiferus terdiri atas suatu lapisan jaringan ikat fibrosa, lamina basalis yg berkembang baik, dan suatu epitel germinal, atau seminiferus, yg kompleks. Tunika propria fibrosa yg membungkus tubulus seminiferus terdiri atas beberapa lapis fibroblas. Lapisan terdalam yg melekat pada lamina basalis terdiri atas sel2 mioid gepeng, yg memperlihatkan ciri otot polos. Sel2 interstisial menempati sebagian besar ruang diantara tubuli seminiferus. Epitel tub.seminiferus terdiri atas 2 jenis sel : sel sertoli, atau sel penyokong dan sel2 yg membentuk garis keturunan spermatogenik. (Jun 10th)

(Jun 12th) 5. Prostate is the largest accessory sex gland of men (about 2 3 4 cm). What are prostate gland consist of? Do you know the characteristic feature of prostate? In good histological sections it is possible to distinguish three concentric zones, mention it! The prostate is a collection of 3050 branched tubuloalveolar glands, all surrounded by a dense fibromuscular stroma covered by a capsule. The glands are arranged in concentric layers around the urethra: the inner layer of mucosal glands, an intermediate layer of submucosal glands, and a peripheral layer with the prostate's main glands. Ducts from individual glands may converge but all empty directly into the prostatic urethra, which runs through the center of the prostate. The prostate has three zones, corresponding to the glandular layers: The transition zone occupies about 5% of the prostate volume, surrounds the prostatic urethra, and contains the mucosal glands emptying directly into the urethra. The central zone occupies 25% of the gland's volume and contains the submucosal glands with longer ducts. The peripheral zone occupies about 70% of the prostate and contains the main glands with still longer ducts. Glands of this area are the most common location of both inflammation and cancer