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THE REPRODUCTIVE SYSTEM Ch 25, Human Anatomy Sonya Schuh-Huerta, Ph.D. The Reproductive System • Involved in the production of gametes, fertilization & procreation of the species • Primary sex organs: – Testes – Ovaries • Accessory sex organs: – Glands – External genitalia The Male Reproductive System The Male Reproductive System • Produce male gamete (= sperm) • Testes are located within the scrotum • The scrotum Skin & superficial fascia surrounding the testes – Positioning provides an environment 3˚ cooler than body temperature! • Dartos muscle = layer of smooth muscle • Cremaster muscle = bands of skeletal muscle surrounding the testes – Elevates the testes The Testes • Contain long coiled seminiferous tubules where sperm are made • Enclosed in a serous sac the tunica vaginalis • Tunica albuginea fibrous capsule of the testes – Divides each testis into 250–300 lobules • Lobules contain 1–4 coiled seminiferous tubules • Epididymis – Comma-shaped structure on posterior testis; where the sperm go after they have developed in the testis The Male Reproductive System Ureter Urinary bladder Peritoneum Seminal vesicle Ampulla of ductus deferens Prostatic urethra Ejaculatory duct Membranous urethra Pubis Rectum Urogenital diaphragm Prostate Bulbourethral gland Corpus cavernosum Corpus spongiosum Spongy urethra Anus Bulb of penis Ductus (vas) deferens Epididymis Testis Scrotum Glans penis Prepuce (foreskin) External urethral orifice Relationship of the Testes to the Scrotum Urinary bladder Superficial inguinal ring (end of inguinal canal) Spermatic cord Testicular artery Ductus (vas) deferens Penis Autonomic nerve fibers Middle septum of scrotum Pampiniform venous plexus Cremaster muscle External spermatic fascia Superficial fascia containing dartos Scrotum muscle Epididymis Tunica vaginalis (from peritoneum) Tunica albuginea of testis Internal spermatic fascia Skin Nerves & Vessels • Arterial supply of the testes – Testicular arteries • Testicular veins arise from the pampiniform plexus – Pampiniform plexus helps keep testes cool! • Testes innervated by parasympathetic & sympathetic divisions of ANS • The spermatic cord contains: – Vas deferens – Testicular blood vessels & nerves – Runs through inguinal canal The Testis & Spermatic Cord Spermatic cord Spermatic cord Blood vessels and nerves Ductus (Vas) deferens Head of epididymis Efferent ductule Rete testis Straight tubule Body of epididymis Duct of epididymis Tail of epididymis Epididymis Testis Seminiferous tubule Lobule Septum Tunica albuginea Tunica vaginalis Cavity of tunica vaginalis Testis Microscopic Anatomy • Scientists once believed that the sperm contained a tiny human or all the material that would give rise to the human (“spermists”) A Seminiferous Tubule of the Testis Seminiferous tubule Areolar connective tissue Interstitial Cells (Leydig cells) Myoid cells Spermatogenic cells Sertoli Cell & nucleus Sperm Microscopic Anatomy • Sertoli Cells – Surround developing sperm – Extend from basal lamina to the lumen – Tight junctions between cells • Blood-testis barrier (protects sperm from immune system!) – Assist sperm production – Secrete testicular fluid & androgen-binding protein (ABP) Microscopic Anatomy • Interstitial cells: • Myoid cells surround seminiferous tubules – Contract rhythmically • Leydig cells – Secrete testosterone (T)! What does T do? • T secretion regulated by LH (Luteinizing Hormone) The Epididymis • Duct of the epididymis is 6 m long (when uncoiled) • Dominated by pseudostratified columnar epithelium – Bears tufts of stereocilia immotile, long microvilli • 20-day journey for sperm to move through epidid. – Chemical changes that give them the ability to swim, undergo the acrosome reaction & fertilize an egg The Epididymis Spermatic cord Blood vessels and nerves Ductus (Vas) deferens Head of epididymis Efferent ductule Rete testis Straight tubule Body of epididymis Duct of epididymis Tail of epididymis Testis Seminiferous tubule Lobule Septum Tunica albuginea Tunica vaginalis Cavity of tunica vaginalis The Epididymis & Vas Deferens Smooth muscle around the duct of the epididymis Loose connective tissue outside the duct Stereocilia Duct of the epididymis Sperm in the lumen Pseudostratified columnar epithelium (a) Duct of the epididymis (110) Lumen Smooth muscle Mucosa Pseudostratified columnar epithelium Internal longitudinal layer Middle circular layer Lamina propria External longitudinal layer Adventitia (connective tissue) (b) Vas deferens (7) Vas Deferens (Ductus Deferens) • Stores & transports sperm • Joins up with ejaculatory duct The Vas Deferens • Trace the course of the Vas deferens Seminal vesicle Ampulla of ductus deferens Ejaculatory duct Bulbourethral gland Vas deferens The Vas Deferens & Urethra Ureter Ampulla of ductus deferens Urinary bladder Prostate Prostatic urethra Orifices of prostatic ducts Membranous urethra Root of penis Seminal vesicle Ejaculatory duct Bulbourethral gland & duct Urogenital diaphragm Bulb of penis Crus of penis Bulbourethral duct opening Ductus deferens Corpora cavernosa Epididymis Shaft (body) of penis Corpus spongiosum Testis Spongy urethra Glans penis Prepuce (foreskin) External urethral orifice Accessory Glands • The Seminal vesicles – Lie on the posterior surface of the urinary bladder – Secretes about 60% of the volume of semen • Fluid contains – – – – – Fructose to nourish sperm Substances that enhance sperm motility Prostaglandins Substances that suppress immune responses against semen Enzymes that clot & then liquefy semen Accessory Glands • The Prostate gland – Encircles the prostatic urethra – Secretes about 25–30% of the volume of seminal fluid – Contains substances that • Enhance sperm motility • Enzymes that clot & then liquefy semen Accessory Glands • The Bulbourethral glands – Pea-sized glands inferior to the prostate gland – Produce a mucus • Mucus enters spongy urethra prior to ejaculation – Neutralizes traces of acidic urine, otherwise this would kill sperm! – Also lubricates urethra Male External Genitalia • Penis internal anatomy – 3 erectile bodies • 1 corpus spongiosum – Surrounds spongy urethra • 2 coropora cavernosa – Contain sinuses, make up most of the penis • Male sexual response – Erection parasympathetic control, allows blood to enter corpora cavernosa – Ejaculation sympathetic control Spermatogenesis • Sperm formation • 400 million sperm formed per day (that’s ~4,000 sperm per heartbeat!) – Begins at puberty, continues throughout man’s entire life – Process takes ~75 days – Cells undergo meiosis, differentiate, & move toward the lumen • • • • • Spermatogonia Primary spermatocytes Secondary spermatocytes Spermatids Sperm TESTIS gonocyte 1° spermatogonium spermatocyte 2° spermatocyte spermatid mature sperm Spermatogenesis • Divided into 3 stages – Stage 1 spermatogonia divide by mitosis • Type A maintain the germ cells (= stem cells) • Type B differentiate into primary spermatocytes – Stage 2 meiosis I & meiosis II • Meiosis I forms 2 secondary spermatocytes • Meiosis II each secondary spermatocyte forms 2 spermatids – Stage 3 Spermiogenesis • • • • The 4 spermatids differentiate into mature sperm Flagellum (tail) formed ( head, midpiece, tail) Form acrosome Shed cytoplasm (compact head, with very little cytosol) Spermatogenesis Spermatogonium (stem cell) Meiosis (early spermatogenesis) Spermiogenesis (late spermatogenesis) Spermatogenesis Mitosis Growth Enters meiosis I and moves to adluminal compartment Meiosis I completed Basal lamina Type A daughter cell remains at basal lamina as a stem cell Type B daughter cell Primary spermatocyte Secondary spermatocytes Meiosis II Early spermatids Late spermatids Sperm (b) Events of spermatogenesis, showing the relative position of various spermatogenic cells Spermiogenesis Golgi apparatus Approximately 24 days Acrosomal vesicle Mitochondria Acrosome Nucleus 1 (a) 2 Spermatid nucleus Centrioles 3 Midpiece Head Microtubules Flagellum Excess Cytoplasm (cytoplasmic droplet) Acrosome 4 Tail 5 6 (b) 7 Control of Spermatogenesis • Spermatogenesis controlled by – Follicle stimulating hormone = FSH (from ant. pituitary) – Testosterone (from testis) • Secretions from Sertoli cells also influence spermatogenesis – Androgen-binding protein concentrates T near developing sperm – Inhibin inhibits FSH (feedback loop) Normal Sperm Parameters & Male Infertility > 20 million (20–150 million) sperm per ml (2–3 ml/ejaculate) > 50% forward motility > 40% normal morphology Male Infertility Disorders Endocrine – Testicular Feminization Syndrome (androgen receptor does not respond to T) Hypothalamic – Kallman’s Syn (no GnRH or olf. neurons) Anatomic – Varicocele Sertoli Cell Only Syndrome Oligospermia = reduced sperm # human sperm Azoospermia = no sperm Asthenozoospermia = reduced motility Chromosomal Defects = Klinefelter’s Syndrome (XXY) Causes of Human Infertility ~15% of couples are infertile low sperm quantity poor morphology poor motility Male infertility contributes to ~½ of cases Causes of Male Infertility Unusual Problems Ovulatory Dysfunction 15% 5% Unknown 10% Female tubal & pelvic pathology 35% Male Factor 35% Endocrine Hypothalamic/Pituitary Anatomic Coital Disorders Environmental Factors Infections/toxins/drugs Sperm abnormalities Genetic/Chromosomal Defects Idiopathic (Speroff, L., Clin Gynecol Endocrin & Infertility, 1999) Cancers of the Male Reproductive System • Testicular cancer – – – – Affects 1 in 50,000 males Commonly from early-stage spermatogenic cells Increase of 50% from 1974 to 1990 Cured in 95% of cases • Prostate cancer – Slow-growing arises from peripheral glands – Increasingly common – Risk factors • Fatty diet • Genetic predisposition The Female Reproductive System Leonardo Da Vinci Female Reproductive System • Produces female gamete (= oocytes/eggs) • Functions to support a developing embryo • Undergoes changes according to the menstrual cycle – Menstrual cycle = the monthly cycle as it affects all reproductive organs in preparation for pregnancy • Includes: – Ovaries, uterine tubes (fallopian tubes), uterus, & vagina The Vagina • Consists of 3 layers – Adventitia fibrous connective tissue – Muscularis smooth muscle – Mucosa marked by transverse folds • Consists of lamina propria & stratified squamous epithelium • Hymen an incomplete diaphragm • Fornix recess formed at the superior part of the vagina The Ovaries • Small, almond-shaped organs – Produce eggs/oocytes!!! • Held in place by ligaments & mesenteries – Broad, suspensory, & ovarian ligaments • Ovarian arteries arterial supply • Innervated by both divisions of ANS Female Internal Reproductive Organs Peritoneum Uterosacral ligament Perimetrium Rectouterine pouch Rectum Posterior fornix Cervix Anterior fornix Vagina Anus Urogenital diaphragm Greater vestibular (Bartholin’s) gland Suspensory ligament of ovary Infundibulum Uterine tube Ovary Fimbriae Uterus Round ligament Vesicouterine pouch Urinary bladder Pubic symphysis Mons pubis Urethra Clitoris External urethral orifice Hymen Labium minus Labium majus The Female Reproductive System Suspensory ligament of ovary Uterine (fallopian) tube Ovarian blood vessels Mesosalpinx Fundus of uterus Uterine tube Lumen (cavity) of uterus Ampulla Ovary Isthmus Infundibulum Mesovarium Broad ligament Fimbriae Mesometrium Ovarian ligament Body of uterus Ureter Uterine blood vessels Isthmus Uterosacral ligament Lateral cervical (cardinal) ligament Lateral fornix Cervix Round ligament of uterus Endometrium Myometrium Perimetrium Internal os Cervical canal External os Vagina Wall of uterus Deep Structures of the Female External Genitalia & Perineum Clitoris Labia minora Labia majora Anus Inferior ramus of pubis Bulb of vestibule Pubic symphysis Body of clitoris, containing corpora cavernosa Clitoris (glans) Crus of clitoris Urethral orifice Vaginal orifice Greater vestibular gland Fourchette Internal Structure of the Ovaries follicle B • Tunica albuginea oocyte – Fibrous capsule of the ovary • Ovarian cortex periphery, where developing oocytes are found • Follicles multi-cellular sacs housing oocytes • Ovarian medulla loose connective tissue – Contains blood vessels, lymph vessels, & nerves Structure of the Ovary Tunica albuginea Cortex Oocyte Degenerating corpus luteum (corpus albicans) Granulosa cells Antral follicle Mesovarium & blood vessels Mature ovarian (Graafian) follicle Germinal epithelium Primary follicles Antrum Oocyte Ovarian ligament Zona pellucida Theca folliculi Medulla Corpus luteum Ovulated oocyte Developing corpus luteum Corona radiata The Fallopian Tubes (Oviducts) • Receive ovulated oocyte • Parts of the fallopian tube – Infundibulum = distal end of uterine tube • Surrounded by fimbriae (finger-like projections) – Ampulla = middle 1/3 of uterine tube • Usual site of fertilization!!! – Isthmus = medial 1/3 of uterine tube; narrows Microscopic Anatomy of Uterine Tubes • Muscular & ciliated aids in transport of oocyte & embryo! Muscularis Mucosa Ciliated columnar epithelium Nonciliated epithelium Lamina propria (a) Cross section through the ampulla (10) (b) Enlargement of the mucosa (180) The Uterus • Lies anterior to rectum, posterior to bladder • Anteverted (anteflexed) usual position of uterus • Parts of the uterus – Fundus = rounded superior portion – Cervix = “neck” of uterus • Cervical canal = connects with vagina inferiorly • Internal os = opening connecting with uterine cavity • External os = inferior opening of cervix (at top of vagina) Supports of the Uterus • Uterus is supported by – Mesometrium anchors uterus to lateral pelvic walls – Lateral ligaments horizontal from cervix & vagina – Round ligaments bind uterus to the anterior pelvic wall Uterine Wall • Wall of the uterus composed of: – Perimetrium, myometrium, & endometrium • Embryo burrows into endometrium • Endometrium has 2 layers – Functional layer – Basal layer Uterine Wall • Uterine arteries send branches to uterine wall & divide into arcuate arteries • Radial arteries reach the endometrium & branch into – Straight arteries to basal layer – Spiral arteries to functional layer • Undergo degeneration (& are shed) and then regeneration with the menstrual cycle The Uterine Wall Lumen of uterus Epithelium Lumen of uterus Epithelium Capillaries Uterine glands Uterine glands Functional layer of the endometrium Venous sinusoids Lamina propria of connective tissue Lamina propria of connective tissue Spiral (coiled) artery Straight artery Endometrial vein Smooth muscle fibers Basal layer of the endometrium Portion of the myometrium Radial artery Smooth muscle fibers Arcuate artery Radial artery Uterine artery The Female Menstrual Cycle & Oogenesis • Monthly menstrual cycle – The recurring cycle of physiological changes to uterus, ovaries, & other reproductive organs due to hormonal fluctuations in ovaries, that occur from the beginning of one menstrual period to the next • Ovarian cycle stimulates maturation of ovarian follicles & oocytes • Uterine cycle prepares uterine wall for implantation The Ovarian Cycle • Follicular phase – 1st half of the ovarian cycle – 6–12 primordial follicles stimulated to develop – Growth stimulated by FSH from ant. pituitary – Primordial follicle primary follicle – As follicles grow larger they gain granulosa & thecal cells layers of follicle that secrete hormones (estrogens, etc.) The Follicular Phase (cont…) • Primary follicles secondary follicles – Corona radiata coat of granulosa cells surrounding oocyte • Secondary follicles enlarge & become – Antral follicles (Antrum = fluid-filled cavity) – Then, become mature Graafian follicle ready to be ovulated – Only 1 dominant Graafian follicle ovulated (usually!) – Rest undergo atresia cell death Graafian follicle OVARY gonocyte primordial follicle 1° follicle 2° follicle Antral follicle mature ovum ovulation The Ovarian Cycle • Ovulation – Occurs about halfway through each ovarian cycle (~Day 14) – 1 mature oocyte ruptures from follicle & exits from 1 ovary • Enters peritoneal cavity – Swept into oviduct by fimbria – Sudden increase in LH (from ant. pituitary) is signal for ovulation! ovulation movie The Ovarian Cycle • Luteal phase – Occurs after ovulation, in last half of the ovarian cycle – Remaining follicle becomes a corpus luteum • Secretes progesterone • Prepares uterus for implantation of an embryo – If no implantation • Corupus luteum dies The Ovarian Cycle 2 Primary 1 Primordial follicle follicles 2 3 3 Secondary follicle Theca folliculi 4 Primary oocyte 1 4 Antral follicle Zona pellucida 8 5 7 Antrum Secondary oocyte 6 7 7 Corpus luteum (forms from ruptured follicle) Secondary oocyte Corona radiata 6 Follicle ruptures; secondary oocyte ovulated 5 Mature ovarian follicle carries out meiosis I; ready to be ovulated Plasma hormone level The Ovarian Cycle LH FSH Days 1 5 Menstrual phase 10 Proliferative phase 15 20 Secretory phase 25 (a) Fluctuation of gonadotropin levels: Fluctuating levels of pituitary gonadotropins (follicle-stimulating hormone and luteinizing hormone) in the blood regulate the events of the ovarian cycle. 28 Primary Vesicular Corpus follicle follicle luteum Secondary Ovulation Degenerating follicle corpus luteum Follicular phase 5 Days 1 Menstrual phase Ovulation (Day 14) 10 Proliferative phase 15 Luteal phase 20 25 Secretory phase 28 (b) Ovarian cycle: Structural changes in the ovarian follicles during the ovarian cycle are correlated with (d) changes in the endometrium of the uterus during the uterine cycle. Oogenesis • Takes many years to complete (~12–51 years!) • Primary oocytes are arrested (stalled) in meiosis I • Surge of LH also causes primary oocyte to compete meiosis I • Oogenesis produces 1 ovum & 3 polar bodies – Polar bodies do not contribute to developing embryo – Are shed & lost • Meiosis II is completed only upon fertilization Oogenesis Before birth Meiotic events Follicle development in ovary Oogonium (stem cell) Follicle cells Oocyte Mitosis Primary oocyte Primordial follicle Primary oocyte (arrested in prophase I; present at birth) Primordial follicle Growth Infancy and childhood (ovary inactive) Each month from puberty to menopause Primary follicle Primary oocyte (still arrested in prophase I) Secondary follicle Spindle Meiosis I (completed by one primary oocyte each month in response to LH surge) First polar body Meiosis II of polar body (may or may not occur) Polar bodies (all polar bodies degenerate) Mature ovarian follicle Secondary oocyte (arrested in metaphase II) Ovulation Sperm Meiosis II completed (only if sperm penetration occurs) Second Ovum polar body Ovulated secondary oocyte The ruptured follicle becomes a corpus luteum and ultimately degenerates. Degenating corpus luteum The Uterine Cycle • • • • Series of cyclic phases of the endometrium Phases coordinate with the ovarian cycle Endometrial phases directed by FSH & LH Phases of uterine cycle – Menstrual phase days 1–5 • Stratum functionalis is shed – Proliferative phase days 6–14 – Secretory phase days 15–28 The Uterine Cycle Structural & hormonal changes Blood vessels Plasma hormone level Endometrial glands Menstrual flow Estrogens Progesterone Days 1 5 10 15 20 25 28 Menstrual Proliferative Secretory phase phase phase (c) Fluctuation of ovarian hormone levels: Fluctuating levels of ovarian hormones (estrogens and progesterone) cause the endometrial changes of the uterine cycle. The high estrogen levels are also responsible for the LH/FSH surge in (a). Functional layer Basal layer Days 1 5 Menstrual phase 10 Proliferative phase 15 20 Secretory phase 25 (d) The three phases of the uterine cycle Menstrual: Shedding of the functional layer of the endometrium. Proliferative: Rebuilding of the functional layer of the endometrium. Secretory: Begins immediately after ovulation. Enrichment of the blood supply and glandular secretion of nutrients prepare the endometrium to receive an embryo. Both the menstrual and proliferative phases occur before ovulation, and together they correspond to the follicular phase of the ovarian cycle. The secretory phase corresponds in time to the luteal phase of the ovarian cycle. 28 Oocyte Loss & Infertility • Follicles lost by atresia/cell death (~1,000/month lost) • Follicles/oocytes lost throughout life • Quality & quantity of oocytes ovarian reserve • Ovarian reserve correlated with fertility • Many reproductive disorders/diseases where # of follicles reduced subfertility or infertilty • Variability among women genes & environment The Life History of a Woman’s Oocyte Pool Fetal Life Conception 12 wks 20 wks Birth Puberty Age ~12 Peak Fertility 20’s Fertility Decline 30’s Menopause Age ~51 1 million oocytes/follicles PGCs ~1,000 oogonia enter meiosis & differentiate Ovulation begins 500,000 oocytes ~25,000 oocytes Ovulation ends <1,000 oocytes PGC migration & proliferation 5-7 million (Langman’s Medical Embryology, 2007) www.istockphoto.com Egg Number Declines with Age • • We can measure a woman’s oocyte pool Studies of genetic & environmental links Follicle Counts in Women 60 50 Transvaginal Ultrasound Image of Antral Follicles 40 AFC AFC (Antral Follicle Count) = Non-invasive window into oocyte pool R2 = 0.27 R2 = 0.28 30 20 10 0 25 30 35 40 45 Age (years) (Schuh-Huerta et al., Hum Reprod 2011 & Hum Genet 2012) Causes of Female Infertility Female Infertility-Related Disorders Various reproductive system cancers and/or radiation therapy (now fertility preservation being done cryopreservation of eggs) Endocrine – Polycyctic Ovarian Syndrome (high androgen levels, cystic (ovaries, metabolic/hormonal abnormalities) Anatomic – Congenital defects, Pelvic inflammatory disease (& scarring) Endometriosis – endometrial tissue growing outside of uterus Premature Ovarian Failure = loss of all follicles before age 40 Early Menopause = loss of all follicles before age 45 Chromosomal Defects = Turner’s Syndrome (XO) Female-produced Anti-sperm antibodies Fertilization, Pregnancy & Childbirth Donating Eggs or Sperm Egg Donors Compensated $6,500–$8,000 Sperm Donors Compensated $100/sample $1,200/month for 3X/week Fertilization • Events leading to fertilization – Sperm binds to the zona pellucida (coat of egg) – Undergoes the acrosome reaction • Releases enzymes to penetrate zona pellucida – Fusion of oocyte & sperm – Cortical & Zona Reactions of egg • Enzymes prevent other sperm from binding to the egg & the zona becomes hardened (prevents polyspermy & protects developing zygote/embryo) – Fertilization chromosomes of male & female gametes join (2 pronuclei fuse; diploid chromosome complement restored) Close Encounters of the Zygotic Kind Mammalian Fertilization 1. Sperm Capacitation 1. Capacitation 2. Chemoattraction 2. Chemoattraction 3. Sperm-ZP Binding 3. Sperm-Zona Pellucida Binding 4. Acrosome Reaction 5. Penetration of the ZP 6. Sperm-Oocyte Binding & Fusion 6. Sperm-Oocyte Binding & Fusion Ca2+ 4. Acrosome Reaction 7. Egg Activation 8. Zona Reaction 5. Penetration of ZP (Dick Bowen, Colorado State) 7. Egg Activation 8. Cortical & Zona Reaction Fertilization Sperm Corona radiata Zona pellucida First polar body Oocyte in second meiotic division (b) Sperm nucleus Acrosome Acrosomal reaction Granulosa cells of corona radiata Zona pellucida Extracellular space Oocyte plasma membrane Cortical granule Oocyte cytoplasm Cortical Fusion of oocyte and sperm plasma reaction membranes Sperm nucleus engulfed by oocyte cytoplasm Early Embryonic Development (a)Zygote (fertilized egg) Uterine tube (b)4-cell stage 2 days (d)Early blastocyst (morula hollows out and fills with fluid). 4 days Blastocyst cavity Sperm Fertilization (sperm meets and enters egg) Oocyte (egg) (e)Implanting blastocyst (consists of a sphere of trophoblast cells and an eccentric cell cluster called the inner cell mass). 7 days Ovary Trophoblast Ovulation Uterus Endometrium Cavity of uterus Blastocyst cavity Inner cell mass Implantation • Blastocyst begins implantation – ~6 days after conception • Blastocyst consists of: – Inner cell mass & outer trophoblast – Trophoblast forms 2 layers • Cytotrophoblast = inner layer; along with extraembryonic mesoderm forms chorion & chorionic villi • Syncytiotrophoblast = outer layer; invades & erodes the endometrium The Placenta • Exchanges across the chorionic villi between maternal & fetal blood – Provide fetus with nutrients & O2 – Dispose of its wastes – Allow hormonal signals to be sent to the mother • By Week 13 the placenta is fully formed & functional Implantation & Growth of Placenta Endometrium Maternal blood vessels Maternal blood vessels Proliferating syncytiotrophoblast Cytotrophoblast Amniotic cavity Bilayered embryonic disc Endometrial epithelium (a) Implanting 71/2-day blastocyst. The syncytiotrophoblast is eroding the endometrium. Lacuna (intervillous space) containing maternal blood Proliferating syncytiotrophoblast Amnion Cytotrophoblast Amniotic cavity Bilayered embryonic disc Yolk sac Extraembryonic mesoderm Chorion being formed (b) 12-day blastocyst. Implantation is complete. Extraembryonic mesoderm is forming a discrete layer beneath the cytotrophoblast. Amniotic cavity Primary germ layers Chorionic villus Ectoderm Chorion Mesoderm Amnion Endoderm Forming body stalk Yolk sac Allantois Extraembryonic mesoderm Lumen of uterus Lumen of uterus Extraembryonic coelom (c) 16-day embryo. Cytotrophoblast and associated mesoderm have become the chorion, and chorionic villi are elaborating. The body stalk forms the basis of the umbilical cord. Implantation & Growth of Placenta Decidua basalis Maternal blood Chorionic villus Umbilical blood vessels in umbilical cord Amniotic sac Amniotic cavity Yolk sac Extraembryonic coelom Lumen of uterus Chorion Decidua capsularis (d) 41/2 -week embryo. The decidua capsularis, decidua basalis, are well formed. The chorionic villi lie in blood-filled intervillous spaces within the endometrium. The embryo is now receiving its nutrition via the umbilical vessels that connect it (through the umbilical cord) to the placenta. The 13-Week Placenta • Embryonic & maternal tissues contribute to the placenta Placenta Decidua basalis Chorionic villi Yolk sac Amnion Amniotic cavity Umbilical cord Decidua capsularis Extraembryonic coelom Uterus Lumen of uterus (e) 13-week fetus – placenta now fully formed and functional Anatomy of the Placenta Placenta Chorionic villi Decidua basalis Maternal arteries Maternal veins Myometrium Umbilical cord Decidua capsularis Uterus Lumen of uterus Chorionic villus containing fetal capillaries Maternal blood in lacuna (intervillous space) Fetal arteriole Fetal venule Amnion Umbilical cord Stratum basalis of endometrium Maternal portion of placenta (decidua basalis) Fetal portion of placenta (chorion) Umbilical arteries Umbilical vein Connection to yolk sac Anatomy of the Placenta • Placental barrier consists of: – All 3 layers of the chorionic villi • Sugars, fats, & O2 diffuse from mother to fetus • Urea & carbon dioxide diffuse from fetus to mother • Syncytiotrophoblast secretes substances that regulate events of pregnancy • Maternal antibodies transported across placenta • Viruses, alcohol, & heroin cross the placental barrier Pregnancy & Childbirth • • • • Gestation 266 days (40 weeks) High levels of progesterone & estrogen maintain pregnancy Parturition childbirth Labor events that expel the infant from the uterus Umbilical cord Placenta Uterus Pubic symphysis Cervix Vagina (a) Dilation (early) Sacrum (b) Dilation (late) Childbirth • Early Labor • Active Labor (regular, increasingly painful contractions; > 4 cm dilated) • Delivery of baby • Delivery of placenta • Avg time of labor ~ 7–12 hrs Perineum Uterus (c) Expulsion Placenta (detaching) Umbilical cord (d) Placental The Mammary Glands • Breasts modified sweat glands – Glandular structure undeveloped in nonpregnant women – Milk production starts at or after childbirth – Before milk production secretion of callostrum (loaded with mom’s antibodies) The Mammary Glands First rib Skin (cut) Pectoralis major muscle Suspensory ligament Adipose tissue Lobe Areola Nipple Opening of lactiferous duct Lactiferous sinus Lactiferous duct Lobule containing alveoli Hypodermis (superficial fascia) Intercostal muscles Cancers of the Female Reproductive System • Ovarian cancer arises from cells in the germinal epithelium • Endometrial cancer arises from the endometrium of the uterus • Cervical cancer slow-growing, arises from epithelium at tip of the cervix; often associated with HPV Cancers of the Female Reproductive System • Breast cancer 2nd most common cause of cancer deaths in women! – 97% occurs in women over 50 – Treatment • Surgical removal of the mass (lumpectomy or mastectomy) • Radiation therapy • Administration of selected hormones • Chemotherapy Breast Cancer (a) Mammogram procedure Malignancy (b) Film of normal breast (c) Film of breast with tumor Embryonic Development of the Sex Organs • Sexual Differentiation • Embryo at 5–6 weeks is sexually indifferent – Mesonephric (Wolffian) ducts future male ducts – Paramesonephric (Mullerian) ducts future female ducts Embryonic Development of the Sex Organs Mesonephros Mesonephric (Wolffian) duct Gonadal ridge Paramesonephric (Müllerian) duct Metanephros (kidney) Cloaca 5- to 6-week embryo: sexually indifferent stage Embryonic Development of the Sex Organs • Development of the external genitalia Genital tubercle Urethral fold Labioscrotal swelling Anus Tail (cut) Urethral groove (a) Indifferent external genitalia; Approximately 5 weeks Sexual Differentiation • Male sexual differentiation begins in Week 7 • SRY = Sex Determining Region of the Y Chromosome initiates male differentiation – Wolffian ducts become • Epididymis • Vas deferens • Ejaculatory duct – Mullerian ducts degenerate Sexual Differentiation • Female sexual differentiation begins Week 8 – Cortical portion of immature ovaries form ovarian follicles – Mullerian ducts become • Uterus • Fallopian tubes • Superior part of vagina – Wolffian ducts degenerate Sexual Differentiation Glans penis Glans clitoris Labioscrotal swellings (scrotum) Urethral folds Labioscrotal swellings (labia majora) Anus Urogenital sinus Urethral folds (labia minora) Anus Glans penis Glans clitoris Penis Scrotum Labia majora Anus Anus (b) Male development Labia minora (c) Female development Puberty • Sexual maturation changes that occur during the period of life between ages ~10–18 • Begins with pulsatile secretion of GnRH from brain • Reproductive organs grow to their adult size • Events of puberty occur in the same sequence in all individuals – Age at which events of puberty occur varies widely – Age of puberty has decreased dramatically Puberty • Male secondary sex characteristics – Enlargement of the scrotum & testes (age ~13) – Appearance of pubic, axillary, & facial hair – Lengthening of vocal folds deepening voice – Musculoskeletal system increases in mass – Sexual maturation mature sperm in seminal fluid Puberty • Female secondary sex characteristics – Budding breasts (avg age ~11) – Other estrogen-induced secondary sex characteristics • Increase in subcutaneous fat • Widening & lightening of the pelvic girdle bones • Appearance of axillary & pubic hair • Estrogen-induced growth spurt from age ~12-17 – Menarche the first menstruation (avg age ~12) Strong correlations between industrialization, better nutrition, body fat (BMI), and decreased age of menarche. more fat tells your brain you’re ready to reproduce! …What hormones/signals might be involved? Reproductive Life Span & Menopause • Female reproductive peak late 20’s • Late 30’s increases in: –rate of follicle loss –miscarriage rates –trisomies & other genetic defects –complications of pregnancy & prematurity –high risk pregnancy (multiples) –infertility • Ovulation & menstruation cease age ~46–54 – No more follicles; ovaries stop secreting estrogen! • Reproductive organs & breasts begin to atrophy • Osteopenia, osteoporosis, & cardiovascular disease risk Questions? What’s Next? Today’s Lab: Reproductive System Mon Lecture: Endocrine System Mon Lab: Endocrine System & Presentations