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• • • • • scrotum = supportive structure for the testes consists of loose skin and superficial fascia that hangs from the root of the penis externally- single pouch separated at the midline by a raphe internally – divided by a scrotal septum into two sacs each containing 1 testis the septum = dartos muscle (smooth muscle) + superficial fascia – • • • dartos is also found in the subcutaneous portion of the scrotal skin each testis is associated with a cremaster muscle – skeletal muscle that is a continuation of the internal oblique exterior location of the testis ensures its internal temperature is at least 2 to 3C lower than the body core contraction of the muscles lifts the scrotal sac closer to the trunk of the body and warms it Male Anatomy Review Reproductive Ducts – Anatomy Review -pressure generated by the Sertoli cells pushes the sperm into a series of ducts within the testes that end up as the epididymis -within the epididymis is the ductus epididymis -also made up of a head, body and tail portion -site of sperm maturation – acquire mobility (14 days) -helps propel sperm into the: -vas (ductus) deferens: conducting tube from testis to urethra -connects to the tail of the epididymis -connects the testes to the urethra -made up of a pseudostratified columnar epithelium with a lamina propria connective tissue plus three layers of smooth muscle -contractions of these muscular layers propel the sperm -spermatic cord supports the vas deferens + blood vessels (testicular artery and the pampiniform venous plexus), lymphatic vessels, the cremaster muscle and autonomic nerves -passes through the inguinal canal • ejaculatory duct – forms from the union of the seminal vesicle and the end of the vas deferens – pass through the prostate gland and terminate in the urethra • urethra: 3 sections: • A. prostatic - runs through the prostate • connects to ducts from the prostate and to the ejaculatory duct • B. membranous - between prostate and penis • through the muscles of the perineum – urogenital diaphragm • C. spongy - through the erectile tissue of the penis Male reproductive glands • • • • • • • • • • glands: seminal vesicles, prostate, bulbourethral glands -produce fluid that combine with sperm to make semen -semen: alkaline, activates sperm cells 1. prostate: surrounds the urethra -forms as an outgrowth of the urethra along with the bulbourethral glands -secretes a thin, milky fluid that enhances sperm motility and neutralizes vaginal fluid 2. seminal vesicles: connect to urethra via the ejaculatory ducts -secretes an alkaline fluid that contains sugars and prostaglandins (stimulates uterine contractions) 3. bulbourethral glands: 2 glands behind the prostate -secrete a fluid that lubricates the penis -conveys urine and semen -body is found externally -body is comprised of two tissue types of erectile tissue surrounded by connective tissue A. corpus cavernosum - large spaces B. corpus spongiosum - smaller spaces -surrounds the urethra -root of the penis is attached to the pelvis -corpus spongiosum enlargens at the tip - glans penis (sensory receptors) -glans penis covered with a loose fold of skin = prepuce Testes -testis: covered by several protective membranes 1. tunica vaginalis – serous membrane derived from the peritoneum, forms during the descent of the testes 2. tunica albuginea – internal to the TV -extends inward to divide the testes into lobules (200-300) -each lobule contains 1 to 3 coiled seminiferous tubules for sperm production - each seminiferous tubule is lined with epithelium that produce sperm - contained within that epithelium are germ cells for sperm production – known as spermatogenic cells or spermatogonia Seminiferous tubules - each seminiferous tubule is lined with an epithelium that produces sperm - contained within that epithelium are germ cells for sperm production – known as spermatogenic cells or spermatogonia - each spermatogonium will form 4 spermatids at the end of meiosis • embedded among the spermatogenic cells of the seminiferous tubules are large cells called Sertoli cells – sustenacular cells – surround the spermatogenic cells and the developing spermatocytes and spermatids – phagocytosis of unused spermatids – produces a blood-testis barrier – this barrier prevents an immune response against the spermatogenic cell surface antigens which may be recognized as foreign • Sertoli cells – produce numerous chemicals involved in spermatogenesis • anti-Müllerian hormone (AMH) - secreted during the early stages of fetal life • inhibin and activins - secreted after puberty, and work together to regulate FSH secretion • androgen binding protein/ABP - facilitate spermatogenesis and sperm maturation • between adjacent seminiferous tubules are the interstitial cells or Leydig cells – for the production of testosterone (androgen) – androgen = hormone for the development of masculine characteristics Spermatogenesis • • • • • • sperm development – from sperm stem cells called spermatogonia each spermatogonium develops in the embryonic testes from primordial germ cells that arise from the yolk sac the spermatogonium remain dormant in the testes until puberty the maturing sperm can be found toward the lumen of the seminiferous tubule most mature = sperm cells or spermatozoa takes 60-75 days to complete Spermatogenesis • • • 1. some spermatogonium break away from the basement membrane of the seminiferous tubule 2. one spermatogonium forms two primary spermatocytes by mitosis (2n = 46) 3. ONE primary spermatocyte starts meiosis I – forms two secondary spermatocytes (n = 23) – • 4. each secondary spermatocyte completes meiosis II and forms 2 spermatids (n) – • however despite having 23 chromosomes, these chromosomes are still comprise of two chromatids 23 chromosomes each made up of one chromatid at the end of meiosis each primary spermatocyte has formed 4 spermatids Spermatogenesis • spermiogenesis – last stage of spermatogenesis • development of spermatids into a sperm cell – spherical spermatids transform into elongated sperm containing an acrosome and bearing a flagellum Sperm • three functions – 1. reach the oocyte – 2. penetrate the oocyte – 3. donate its chromosomes to the oocyte • major parts – 1. head: contains the nucleus with 23 highly condensed chromosomes (one chromatid) – 2. acrosome: covers the anterior 2/3 of the head • contains digestive enzymes to dissolve the protective barriers surrounding the oocyte – 3. midpiece • contains mitochondria arranged in a spiral • also contains a pair of centrioles for the production of the microtubules for the tail – 4. tail or flagellum • made up of microtubules • principal piece – longest portion of the tail • end piece – terminal portion of the tail • 300 million made each day • 60 um long -release of gonadotropic releasing hormone (GnRH) from the neurosecretory cells of the hypothalamus -GnRH travels to the anterior pituitary via the hypophyseal portal system -in response - the gonadotrophs of the anterior pituitary gland produce and release the 2 gonadotropins 1. Follicle Stimulating Hormone - FSH 2. Leutenizing Hormone - LH 1. Follicle stimulating hormone – works with testosterone to stimulate spermatogenesis -synergistic action by FSH and testosterone on the Sertoli cells -FSH binds to the surface of the Sertoli cell -testosterone and its receptor is internalized by the Sertoli cell - together FSH + testosterone results in secretion of androgen-binding protein by Sertoli cells -ABP binds to testosterone and promotes better spermatogenesis -GnRH and FSH release are both inhibited by the release of inhibin (by the Sertoli cells) 2. Leutinizing hormone - stimulates male hormone production by the Leydig cells -testosterone synthesized from cholesterol in the testes -testosterone stimulates the final stages of spermatogenesis -suppresses GnRH and LH synthesis by negative feedback Testosterone • two major forms: testosterone and 5-dihydrotestosterone (5-DHT) • testosterone and DHT both bind to same receptors – receptors are found within the nuclei of the target cells Testosterone • effects – 1. prenatal development • testosterone stimulates development of the epididymus, vas deferens, ejaculatory ducts and seminal vesicles – gonads develop during the 5th week of gestation from two sets of ducts: 1) Wolffian ducts (males) 2) Mullerian ducts (females) – therefore the embryo has the potential to develop into either sex – BUT “maleness” determined by a gene called SRY – sex determining region of the Y chromosome – SRY protein expression induces differentiation of Sertoli cells – Sertoli cells secrete anti-Mullerian Hormone– apoptosis within the Mullerian ducts which inhibits the development of female structures -in response to hCG – Leydig cells begin to synthesize testosterone Testosterone – 2. development of male sexual characteristics – 3. development of sexual function • male sexual behavior • spermatogenesis • libido in both males and females – 4. stimulation of anabolism • stimulate protein synthesis in both bone and muscle tissue Testosterone • synthesis and secretion is controlled by a negative feedback system • increased testosterone promotes the production of inhibin from the Sertoli cell • decreased testosterone promotes the production of activin from the Sertoli cell -ovary: production of egg -surface is covered with a germinal epithelium (simple epithelium) – does NOT give rise to the ova! -next layer is = tunica albuginea – dense irregular connective tissue capsule -outer cortex- granular tissue due to the presence of tiny ovarian follicles - inner medulla - connective tissue with blood & lymphatic vessels and nerves Oogenesis and Follicular Development • • • • • • begins before birth early fetal development – primordial germ cells from the yolk sac migrate into the developing ovaries differentiate to form oogonia (diploid stem cells) most of these cells degenerate by atresia several oogonia split into primary oocytes (via mitosis) before birth primary oocytes enter and stop at prophase I of meiosis – primary oocyte is surrounded by a layer of follicular cells = primordial follicle – continue to develop into primary follicles Oogenesis and Follicular Development -release of FSH and LH each month causes the development of several follicles and their oocytes -one will continue on to develop and being ovulated -primary follicle – primary oocyte surrounded by several layers of epithelial cells called granulosa cells -develops a clear glycoprotein layer between the oocyte and the granulosa cells – zona pellucida -the outermost granulosa cells develop into two layers (theca layers) – follicle is now known as the secondary follicle -secondary follicle begins to accumulate fluid in the center of the follicle (antrum – mature secondary follicle) (immature secondary follicle Oogenesis and Follicular Development -secondary follicle begins to accumulate fluid in the center of the follicle (antrum) -innermost granulosa cells firmly attach to the zona pellucida = corona radiata -oocyte is still considered a primary oocyte since it hasn’t finished meiosis I Oogenesis and Follicular Development -secondary follicle becomes larger and is called the tertiary or mature Graafian follicle -inside the tertiary follicle is the secondary oocyte which has completed meiosis I and has stopped at metaphase II – two haploid cells are actually found within the tertiary follicle -these haploid cells are uneven in size but each have 23 chromosomes (two chromatids each - 46) -smaller cell – first polar body (discarded nuclear material) -larger cell – secondary oocyte -receives most of the cytoplasm and has 23 chromosomes -ovulated as the tertiary follicle ruptures Oogenesis and Follicular Development • ovulation – expulsion of the secondary oocyte into the pelvic cavity with the first polar body and corona radiata • fertilization – union of egg and sperm – penetration of the sperm into the secondary oocyte results in the resumption of meiosis II – the secondary oocyte splits again into two cells of unequal size (n) – larger one is called the ovum and the smaller one is the second polar body – combination of the ovum and the sperm results in the formation of the zygote – the first polar body splits also into two haploid cells – therefore meiosis of the primary oocyte produces one haploid ovum and three haploid polar bodies that degenerate secondary tertiary • uterus: receives and nourishes the embryo • -comprised of a body, a curved portion (fundus) and the cervix • • • -uterine wall outer perimetrium, muscular myometrium and inner endometrium -endometrium: mucosal layer covered with epithelium -rich blood supply, sloughed off during menstruation • uterine tubes (Fallopian tubes): fertilization of ovum & conduction of ovum or zygote from ovary to uterus • -expands at end near the ovary = infundibulum with fimbrae (fingers) for the • “catching” of the released egg -lined with a mucosal layer and columnar epithelium with cilia -are also cells with microvilli rather than cilia – produce a nutritive fluid for the egg • cervix: projects into the vaginal canal Female Reproductive Cycle • two cycles – 1. ovarian: during and after the maturation of the oocyte – 2. uterine: concurrent series of changes in the endometrium of the uterus to prepare it for embryo implantation -GnRH causes release of FSH and LH from anterior pituitary -FSH initiates follicular growth – primary secondary -LH stimulates the maturation of follicles into tertiary -both LH and FSH stimulate the secretion of estrogens from the follicle -called follicular estrogens -3 major types of estrogens: 1. beta-estradiol 2. estrone 3. estriol 4. other smaller quantities -follicular estrogens = estrogens made by the follicle: a. promote the development of the female reproductive structures, secondary sex characteristics and the mammary glands, increase protein anabolism, including bone synthesis c. lower blood cholesterol d. inhibit the release of GnRH, FSH and LH -LH triggers ovulation and results in development of corpus luteum -corpus luteum produces and releases progesterone and some estrogen plus relaxin and inhibin -estrogens from the corpus luteum are called luteal estrogens -estrogens and progesterone regulate pregnancy, menstruation, secondary sex characteristics & development of sex organs at puberty -relaxin – relaxes the uterus by inhibiting contractions of the myometrium -inhibin - inhibits secretion of FSH and LH 1. Menstrual Phase A. Ovarian events – FSH increase causes development of primary follicles and primary oocytes B. Uterine events – 50-150 mL of blood, tissue fluid, mucus and epithelial cells -shed from the stratum functionalis -occurs because of declining levels of E and P – loss of stratum functionalis - leaving the stratum basalis intact 2. Preovulatory Phase – most variable in length A. Ovarian events – secretion of E and inhibin from the secondary follicles -one secondary follicle outgrows the rest to become the dominant follicle -the dominant follicle secretes E and I which causes an inhibition of FSH and a decrease in the stimulation of other follicles -the dominant follicle develops into the Graafian follicle -the GF continues to increase its estrogen production B. Uterine events – E stimulates the repair of the stratum functionalis -increase in arteriole size and blood supply to the SF post-menstrual phase pre-menstrual phase • 3. Ovulation • A. Ovarian events – rupture of the GF usually around day 14 • ovulated secondary oocyte remains surrounded by its corona radiata and its zone pellucida • triggered by a positive feedback system – high levels of E at the end of the pre-ovulatory phase increases the secretion of GnRH, which then increases the release of LH • increased LH induces rupture of the GF about 9 hours after the LH peak • B. Uterine events - none • 4. Postovulatory Phase – most consistent part of the cycle (14 days) – A. Ovarian events – the mature graafian follicle collapses and bleeds - the development of a blood clot results as the follicle induces bleeding – follicle is now called the corpus hemorrhagicum • follicle is transformed into corpus luteum cells under the influence of LH • luteal cells produce hormones - progesterone, estrogen, relaxin and inhibin – progesterone and estrogen are now negative feedback signals for inhibition of GnRH – together with inhibin GnRH release Stratum functionalis • 4. Postovulatory Phase – most consistent part of the cycle (14 days) – A. Ovarian events • if the ovum is NOT fertilized, the CL degenerates into the corpus albicans • resulting decrease in P, E and Inhibin results in the release of GnRH, FSH and LH (loss of negative feedback) - new follicular growth begins • if fertilized – the CL persists beyond 2 weeks by the secretion of human chorionic gonadotropin (hCG) hormone produced by the developing embryo (8 days postfertilization) corpus luteum corpus albicans post-menstrual phase pre-menstrual phase B. Uterine events – P and E produced by the corpus luteum promotes the growth and vascularization of the endometrium and its thickening to about 12-18 mm -endometrial glands within the endometrium begin to secrete glycogen – energy for the fertilized egg Summary Birth Control Methods • • • • • Surgical Hormonal Mechanical barriers Periodic abstinence Coitus interruptus Reproductive disorders • Males – – – – • Females – – – – – – • testicular cancer prostate concer erectile dysfunction (ED) benign prostatic hyperplasia PMS PMDD Endometriosis Ovarian, uterine cysts Ovarian, uterine, cervical cancer vulvovaginal candidiasis Both – UTI – STDs – gonorrhea, syphillis, chlamydia, genital herpes, genital warts Fertilization & Pregnancy -fertilization in the upper third of the oviduct/fallopian tube -fertilization = union of egg and sperm -plasma membrane of the egg is surrounded by an extracellular matrix = zona pellucida and a ring of follicular cells = corona radiata (nourishment in the follicle) -after fertilization = zygote Fertilization 1. sperm penetrates corona radiata 2. several sperm contact the zona pellucida -one of the glycoproteins within the ZP (ZP3) acts as a receptor for the sperm -binding causes dissolution of the acrosome and release of digestive enzymes (acrosomal reaction) 3. ONE sperm penetrates the plasma membrane of the egg 4. immediate change in the oocyte cell membrane (depolarizes) - binding results in release of intracellular calcium which stimulates exocytosis of secretory vesicles whose contents inactivate ZP3 and harden the zona pellucida to make it impervious to more sperm 5. oocyte releases the hardened zona pellucida away from the egg surface 6. fusion of the sperm with nucleus of the egg -before fusion the secondary oocyte must complete meiosis II and form the ovum embryonic stage: week 2 to week 8 -after sperm penetration and ovum development the nuclei of the egg and sperm undergo changes to become pro-nuclei -union of sperm and egg pro-nuclei nuclei forms the zygote -first cell division = embryo -first division takes place 24 hours post-fertilization – takes 6 hours to complete -each succeeding division takes less time -72 hr stage = 16 cells -96 hr stage = morula (embryo is the size of the original ovum, filled with cells (blastomeres) -day 4 – formation of morula and passage into the uterine cavity -endometrial glands release a glycogen-rich fluid = uterine milk -enters into the morula -day 5 -the fluid begins to collect in the morula and reorganizes them around a fluid-filled cavity = blastocoel -embryo is now called a blastula or blastocyst (50-150 cells) -outer layer = trophoblast - forms extraembryonic tissues (e.g. chorion, amnion) -inner cell mass at one end - totipotent embryonic stem cells -by the end of day 5, the blastocyst digests a hole in the ZP and squeezes through it to undergo implantation Implantation • embryo attaches after about 6 days • usually in the fundus or the body of the uterus • orients its inner cell mass toward the uterus • 7 day – the endometrium becomes more vascularized • 9 days – completely embedded • following implantation, the endometrium is called the decidua – several layers with defined functions -second week of development - the inner cell mass flattens into an embryonic disk (hypoblast and epiblast) -hypoblast = primitive endoderm -epiblast = primitive ectoderm -amniotic cavity forms between the embryonic disc and the trophoblast -surrounded by an amniotic membrane – develops from the epiblast -fills with amniotic fluid – filtrate from maternal blood at initial stages -formation of the yolk sac below the disc - from the hypoblast -forms blood cells, gives rise to sex cells and the stem cells of the immune system -also forms part of the embryonic digestive tube -portion will also become part of the umbilical cord -the outer trophoblast cells develops into part of the chorion (to connect to the mother) -these trophoblast cells will secrete digestive enzymes that allow the embryo to burrow into the endometrium -also secrete hCG – rescues the corpus luteum from degeneration • day 15: embryonic disk undergoes gastrulation to form the gastrula embryonic stage – formation of the three embryonic germ layers by differentiation of the ES cells within the embryonic disc • epiblast form a specialized region = primitive streak – – – – – clearly establishes a head and tail orientation head end the streak enlargens to form the primitive node cells from the epiblast move inward through the primitive streak some cells displace the hypoblast and form the endoderm other cells are retained in the area and form the mesoderm • mesoderma forms a loose connective tissue = mesenchyme – cells remaining in the epiblast form the ectoderm -portions of the mesoderm that do not form the notochord segment into sections called somites -> specific body regions and structures -in front of the primitive streak forms the primitive node – head and associated structures -mesodermal cells from the primitive node form a hollow tube near the future head of the embryo - become the notochord (day 22-24) (progenitor to the vertebral column) -four weeks of development - embryo forms a tubular structure -embryo begins to form definitive structures: -neural folds of ectoderm -> nervous system (brain and spinal cord) ** neurulation occurs by induction (one tissue influences the development of another) -e.g. nervous system requires the mesodermal cells of the notochord