The Reproductive System

The reproductive system becomes fully active during puberty.

The primary sex organs (gonads) are testes in males and ovaries in females

Gonads produce gametes and secrete sex hormones

Testes produce sperm through spermatogenesis

Ovaries produce ova through oogenesis

Accessory reproductive organs are ducts, glands and external genitalia

Anatomy of the Male Reproductive System

The Scrotum

Sac of skin and superficial fascia that houses testes in left and right compartments created by the presence of a midline septum.

Temperature of scrotum must be ~ 3°C lower than core body temperature for production of viable sperm

Temperature maintained by contraction and relaxation of dartos and cremaster muscles

Dartos

Smooth muscle layer in fascia - wrinkles skin, contraction draws scrotum up to reduce heat loss, relaxation allows scrotum to assume a lower position, decreasing temperature

Cremaster

SkM from internal oblique, suspends testes, contraction pulls testes close to abdominal wall, relaxation allows descent away from body, decreases temperature

The Testes

Located within scrotum; produce male gametes (sperm)

Each testis is surrounded by 2 tunics: outer tunica vaginalis formed from peritoneum and inner tunica albuginea, formed from fibrous CT

Septa divide each testis into 250-300 lobules

Each lobule contains 1-4 seminiferous tubules, where sperm is produced

Seminiferous tubules from each lobule converge to form tubulus rectus that conveys sperm to posterior rete testis

Sperm travels then from rete testis to efferent ductules to epididymis

Interstitial cells (Leydig cells): surround seminiferous tubules; produce androgens (testosterone)

Testicular arteries arise from abdominal aortas and supply blood to testes; testicular veins drain testes

Spermatic cord: connective tissue sheath enclosing blood vessels, lymphatics and nerves

Testicular cancer is most common cancer in young men; treatment is surgical removal of tumor followed by radiation and chemotherapy

The Penis

The penis is the male copulatory organ; releases sperm produced by testes.

Male external genitalia consists of the penis and scrotum

Male perineum: diamond-shaped region bounded by pubic symphysis, coccyx and ischial tuberosities

Penis made up of attached root and free body or shaft ending in enlarged tip called glans penis

Prepuce (foreskin): cuff of skin covering penis; may be removed by circumcision

Erectile tissue: network of connective tissue and smooth muscle with vascular spaces that become filled with blood during sexual excitement

Corpus spongiosum: surrounds spongy urethra

Corpora cavernosa: paired dorsal erectile bodies

The Male Duct System

The Epididymis

A coiled tube (about 20 feet long when uncoiled) that delivers immature sperm from testis to ductus deferens, takes about 20 days.

During this journey sperm gain ability to swim.

Sperm are ejaculated from the epididymis - smooth muscle contracts and propels sperm into ductus deferens.

Can be stored for several months but if not ejaculated will be phagocytized by epididymal epithelial cells.

The Ductus Deferens (vas deferens) and Ejaculatory Duct

Propels live sperm from epididymis to urethra.

The ductus deferens is a long (18 inches) tube that runs from epididymis upward anterior to pubic bone into pelvic cavity, loops over ureter and descends posteriorly along bladder, where it joins with seminal vesicle to form ejaculatory duct.

The ejaculatory duct passes into prostate gland and empties into urethra.

 

The Urethra

Terminal portion of male duct system, carries both urine and semen,

Regions:

Prostatic urethra - surrounded by prostate

Membranous urethra - in urogenital diaphragm

Spongy or penile urethra - runs thru penis, opens at external urethral orifice. Contaihs urethral glands that secrete mucus just before ejaculation

Accessory Glands

The Seminal Vesicles

Located on posterior wall of bladder

Secrete seminal fluid: a yellowish viscous alkaline fluid containing fructose (sugar), ascorbic acid, a coagulating enzyme and prostaglandins.

Sperm and seminal fluid mix in ejaculatory duct and enter prostatic urethra during ejaculation.

The Prostate

Encircles urethra just inferior to bladder

Secretes a milky, slightly acidic fluid containing citrate, enzymes and prostate-specific antigen (PSA) that enters prostatic urethra during ejaculation and helps activate sperm.

Prostate gland hypertrophy (BPH, benign prostatic hypertrophy) affects nearly every elderly male.

Compresses urethra, increases risk of bladder infections and renal damage.

Treatments include microwaves, radio-frequency radiation, drugs (finasteride, inhibits dihydrotestosterone production) and transurethral needle ablation (TUNA)

Prostate cancer is second most common cancer in men (behind lung cancer).

The Bulbourethral Glands (Cowper's glands)

Small glands inferior to prostate gland

Produce thick clear mucus prior to ejaculation that neutralizes acidic urine in urethra

Semen

A mixture of sperm and accessory gland secretions

Provides nutrients and transport medium for sperm and chemicals (relaxin) that facilitate movement.

Fructose provides fuel.

Prostaglandins decrease viscosity of mucus at uterine cervix and stimulate reverse peristalsis of uterus and uterine tubes to move sperm through female reproductive tract.

Alkalinity of semen due to bases (spermine) helps neutralize acidic environment of male urethra and female vagina

Seminalplasmin: antibiotic in semen that destroys bacteria

Contains clotting factors to clot and fibrinolysin to liquefy semen

Physiology of Male Reproductive System

Male sexual response

Erection

Results from engorgement of erectile bodies in penis with blood

During sexual excitement, a parasympathetic reflex releases nitric oxide, which dilates arterioles supplying erectile tissue

Corpora cavernosa expand, enlarging and stiffening penis and compressing drainage veins

Ejaculation

Propulsion of semen from male duct system

Sympathetic spinal reflex sends impulses to nerves serving genital organs: reproductive ducts and accessory glands contract, emptying contents into urethra.

Bladder sphincter muscle constricts, preventing urine release of reflux of semen into bladder

Bulbospongiosus muscles of penis undergo series of contractions, propelling semen along urethra

Spermatogenesis

Sperm formation by meiosis in seminiferous tubules of testes

Begins occurring during puberty and continues throughout life

Normally ~ 400 million sperm produced each day

Terms:

diploid (2n): normal chromosome number in most body cells; 46 in humans, or 23 pairs of homologous chromosomes (paternal and maternal chromosome of same chromosome number)

haploid (n): chromosome number in gametes; each human gamete only contains 23 total chromosomes (only 1 of each homologous pair)

 

Meiosis

Consists of 2 nuclear divisions, meiosis I and meiosis II

Forms gametes; reduces chromosome number from 2n to n in gametes

After DNA replication is completed the identical copies of each chromosome remain attached. At this point each chromosome consists of two sister chromatids (chromatid: one chromosome of a duplicated chromosome)

Meiosis I: reduction division (2n to n)

Synapsis: during prophase I, homologous chromosomes (maternal and paternal, each consisting of two sister chromatids) pair, forming tetrads.

Crossovers (chiasmata) occur as chromosomal arms wrap around each other and exchange genetic information.

Independent assortment: during metaphase I, homologous chromosomes line up in pairs at metaphase plate.

The maternal or paternal chromosome of each homologous pair can be on either side of the equator, so each daughter cell produced from meiosis I has a mixture of maternal and paternal chromosomes.

Both synapsis and independent assortment lead to genetic variation in gametes

The resulting daughter cells are considered to be haploid because the sister chromatids remain joined and are officially still one chromosome.

Meiosis II

Equatorial division (chromatids distributed equally)

Mitotic-like division; duplicated chromosomes (sister chromatids) separated

Summary of Events in Seminiferous Tubules

Mitosis of spermatogonia: forming spermatocytes

Spermatogonia divide to form type A cell and type B cell

type A cell remains in basal compartment in spermatogonia population

type B cell moves to adluminal compartment and becomes primary spermatocyte, destined to form 4 sperm cells

Meiosis: spermatocytes to spermatids

Meiosis I: primary spermatocyte forms 2 secondary spermatocytes

Meiosis II: each secondary spermatocyte forms 2 spermatids

Spermiogenesis: spermatids to sperm

Each spermatid undergoes changes to form sperm cell

At one end of nucleus, head region forms, including a tightly enclosed nucleus with an acrosome (contains hydrolytic enzymes for penetration of egg cell) at top

At other end, tail region forms, with a flagellum forming from centrioles and attached to the head region by a midpiece containing many mitochondria (supplying energy for moving flagellum)

Role of the Sustentacular cells

Sustentacular cells (Sertoli cells) surround cells of seminiferous tubules and connect to one another by tight junctions which form 2 compartments (basal and adluminal)

Junctions form blood-testis barrier that prevents immune cell targeting of sperm

Hormonal Regulation of Male Reproductive Function

The Brain-Testicular Axis

Gonadotropin-releasing hormone (GnRH) release from hypothalamus controls release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from anterior pituitary.

FSH stimulates sustentacular cells to release androgen-binding protein (ABP), which causes spermatogenic cells to bind testosterone and begin spermatogenesis

LH binds to interstitial cells and stimulates them to secrete testosterone

Testosterone feeds back (negative feedback) to hypothalamus and anterior pituitary, inhibiting release of GnRH and tropic hormones.

Inhibin is the "sperm count modulating hormone". Inhibin is released by sustentacular cells and inhibits release of FSH from anterior pituitary and GnRH from hypothalamus when sperm counts are high. When the sperm count falls below 20 million/ml inhibin secretion is inhibited.

Since development of male reproductive structures depends on prenatal and early neonatal secretion of male hormones, gonadotropin and testosterone levels are at about mid-pubescent levels in infants, but quickly drop back to normal levels and remain low throughout childhood.

Puberty can occur because the threshold for inhibition of the hypothalamus by testosterone rises, causing release of more GnRH, which stimulates release of more testosterone. The inhibition threshold continues to rise until the adult level is reached.

At that point mature sperm can be found in the semen.

Mechanism and Effects of Testosterone Activity

Some target cells require conversion of testosterone to another steroid (dihydrotestosterone (DHT) in prostate, estradiol in brain) to exert its effects.

Testosterone also controls appearance of secondary sex characteristics in males and boosts metabolism.

Axillary hair, pubic hair, body hair appear

Skin becomes oily

Laryngeal folds thicken, voice deepens

Bones grow and increase density

Muscle mass increases

Stimulates sex drive (also in females to some extent, although DHEA, produced by the adrenal seems more important in female libido)

Masculinizes the embryonic brain and continues to have effects throughout life.

 

Anatomy of Female Reproductive System

Ovaries

Female gonads; produce oocytes and female sex hormones (estrogens and progesterone)

Flank uterus on each side; held in place within peritoneal cavity by parts of broad ligament (suspensory ligament and mesovarium)

The ovarian ligament anchors the ovary to the uterus.

Ovarian arteries (branch from abdominal aorta) and serve ovaries

Ovaries are surrounded externally by tunica albuginea and germinal epithelium

Outer cortex houses follicles; inner medulla contains blood vessels and nerves

Ovarian follicles: in cortex; contain immature egg (oocyte) encased by one or more cell layers (1 layer = follicle cells; more than 1 layer = granulosa cells)

Primordial follicle: one layer of squamous cells enclose oocyte

Primary follicle: 2 or more layers of cuboidal or columnar cells surround oocyte

Secondary follicle: has central fluid-filled cavity (antrum)

Vesicular (Graafian) follicle: follicle bulges from ovary surface; oocyte sits on stalk of granulosa cells at one side of antrum

Ovulation: ejection of oocyte from follicle and ovary

Corpus luteum: structure formed from follicle cells following ovulation; eventually degenerates

 

Graafian Follicle

Female Duct System

The Uterine Tubes (Fallopian tubes or Oviducts)

Receive ovulated oocyte from ovary and provide site for fertilization.

The infundibulum is an open funnel-shaped structure with ciliated fingerlike projections called fimbriae that drape over the ovary.

The oocyte is ovulated into peritoneal cavity; cilia of fimbriae sweep oocyte into uterine tube

Fertilization normally occurs in the ampulla, the expanded curved portion of uterine tube.

The constricted region that leads into uterus is the isthmus.

Smooth muscle sheets in wall of uterine tube and mucosa with ciliated cells aid in carrying oocyte toward uterus.

Uterine tubes are covered by peritoneum and supported by mesentery called the mesosalpinx.

The Uterus

The uterus is a hollow, thick-walled organ in pelvis that receives, retains and nourishes a fertilized ovum.

Consists of fundus, body and cervix from superior to inferior

Cervix (neck) projects into vagina

Cervical canal communicates with vagina via external os and with uterus via internal os

Cervical cancer: caused by certain types of human papillomavirus (HPV); can be diagnosed by Pap (Papanicolau) smear

Mucosa contains mucus-secreting cervical glands, mucus forms a plug between the cervix and vagina

Supports of uterus: mesometrium of broad ligament, lateral cervical ligament, uterosacral ligaments and round ligaments

The Uterine Wall

The uterine wall is composed of 3 layers:

Perimetrium: outermost serous layer; visceral peritoneum

Myometrium: middle smooth muscle layer; contraction of muscle bundles expels baby during childbirth

Endometrium: mucosal lining of uterine cavity; simple columnar epithelium; site of implantation of embryo for development

Stratum functionalis (functional layer): undergoes cyclic changes in response to ovarian hormones; shed during menstruation

Stratum basalis (basal layer): forms new functional layer after menstruation

Blood supply: uterine arteries > arcuate arteries(myometrium) > radial branches(endometrium) > straight arteries (basal layer) and spiral (coiled) arteries (functional layer)

The Vagina

The vagina is a thin-walled tube between bladder and rectum extending from cervix to the exterior.

Provides passageway for delivery of baby, for menstrual flow and for delivery of semen (and sperm) to uterine tube.

The urethra is embedded in anterior wall.

The wall consists of outer fibroelastic adventitia, smooth muscle muscularis and mucosa of stratified squamous epithelium with ridges (rugae).

Cervical mucous glands supply mucus to mucosa; pH of vagina is normally acidic due to metabolism of sugars by resident bacteria (prevents infection).

Hymen: incomplete mucosal partition covering vaginal orifice that is normally ruptured during first sexual intercourse.

The vaginal fornix is a recess at the cervical end of the vagina, where the vagina loosley surrounds the cervix.

External Genitalia (Vulva)

Mons pubis: fatty rounded area overlying pubic symphysis

Labia majora: elongated skin folds running posteriorly from mons pubis and enclosing labia minora.

Labia minora enclose recess called vestibule, which contains the external opening of urethra (anteriorly) and vagina (posteriorly).

The greater vestibular glands (analagous to bulbourethral glands) are found on either side of the vaginal opening.

Secrete mucus into the vestibule to keep it moist and lubicated (facilitates intercourse).

Clitoris: small protruding erectile tissue (corpora cavernosa) hooded by prepuce formed by junction of labia minora folds

Perineum: diamond shaped region surrounding external genitalia

Mammary Glands

Present in both sexes; normally only function in females.

Produce milk and nourish newborn baby.

Composed of modified sweat glands contained within a rounded skin-covered breast, anterior to pectoral muscles.

Glands consist of lobes separated form each other by fat and fibrous CT forming suspensory ligaments that support breasts.

Lobules within lobes contain alveoli that produce milk when a woman is lactating following childbirth.

Milk collects in lactiferous sinuses and is passed into lactiferous ducts, which open to the outside of the nipple.

Invasive breast cancer is the most common cancer of U.S. women, usually arises from epithelial cells of ducts

Known risk factors include: early onset menses and late menopause; no pregnancies or first pregnancy later in life; previous history of breast cancer; family history of breast cancer (possible risk factors include overexposure to estrogens, cigarette smoking and alcoholism)

Hereditary forms (~ 10% of all cases) often stem from mutations in breast cancer susceptibility genes BRCA1 and BRCA2 (mutations in these genes put women at risk for developing breast or ovarian cancer at some time in their lives).

Can be detected by breast self-examination and mammography

Treatment includes radiation and chemotherapy, and surgery (radical mastectomy has been mostly replaced by lumpectomy or, if necessary, simple mastectomy)

Physiology of Female Reproductive System

Oogenesis

Ovum formation by meiosis in follicles of ovaries

Oogonia in fetal period in females rapidly divide and transform into primary oocytes in primordial follicles (~ 2 million by birth)

Primary oocytes begin meiosis I, but arrest in prophase I

Starting at puberty, "one" follicle is chosen each month (from ~ 250,000 remaining) to complete meiosis I, resulting in a secondary oocyte receiving most of the cytosol and a small polar body

The secondary oocyte begins meiosis II, but arrests in metaphase II (awaiting fertilization in oviduct to complete meiosis II); the polar body may divide to form 2 smaller polar bodies

The secondary oocyte is ovulated and is picked up by uterine tube; if fertilization occurs, following sperm entry meiosis II is completed, forming the ovum and another polar body

The end result of complete oogenesis is 3 small polar bodies and one very large ovum (only the ovum is a functional female gamete); the ovum contains most of the cytosol, with ample nutrients for the 7 day journey to the uterus

 

Ovarian Cycle

Monthly series of events associated with maturation of egg

The Follicular phase

The period of follicle growth; days 1-14 (may vary considerably)

A primordial follicle becomes primary follicle upon activation, the squamous cells grow and become cuboidal cells.

The primary follicle becomes secondary follicle when the follicular cells proliferate and form stratified epithelium known as granulosa cells around the oocyte. The granulosa cells are connected to the oocyte by gap junctions.

A layer of connective tissue condenses around the follicle, forming the theca folliculi. The theca folliculi and granulosa cells produce estrogens.

Inner thecal cells produce androgens.

Granulosa cells convert androgens to estrogens.

The oocyte secretes the zona pellucida, forming a capsule around the follicle.

The final stage of conversion to a secondary follicle occurs when clear liquid accumulates between the granulosa cells and forms a fluid-filled cavity called the antrum.

The secondary follicle becomes vesicular follicle when the oocyte and a surrounding capusule of granulosa cells is isolated by the fluid-filled antrum and the primary oocyte completes meiosis I to form the secondary oocyte and first polar body.

The granulosa cells signal the oocyte so that it doesn't complete meiosis at this time.

Ovulation

The bulging ovary wall ruptures and releases secondary oocyte into peritoneal cavity; ~ day 14.

Several follicles are always maturing but the dominant follicle matures faster by becoming more sensitive to FSH faster and is at its peak when the LH surge stimulates ovulation. The other follicles degenerate and are reabsorbed.

Fraternal twins: more than one oocyte ovulated, and each fertilized by different sperm (~1-2% of ovulations are multiple oocytes).

Identical twins: one oocyte fertilized by one sperm, and during early embryogenesis cells divide into separate embryos.

The Luteal Phase

The period of corpus luteum activity; days 14-28

After ovulation, ruptured follicle collapses, antrum fills with clotted blood and follicle grows into endocrine gland called corpus luteum

The corpus luteum secretes progesterone and some estrogen

If pregnancy occurs, corpus luteum continues to produce hormones until the placenta can assume its role; otherwise, corpus luteum degenerates within ~ 10 days

Hormonal Regulation of Ovarian Cycle

Establishing the Ovarian Cycle

As ovaries grow in childhood they secrete small amounts of estrogens, which inhibit hypothalamic release of GnRH.

The hypothalamus becomes less sensitive to inhibition by estrogen and releases GnRH rhythmically, which stimulates the anterior pituitary to release FSH and LH.

FSH and LH stimulate ovarian estrogen production.

Gonadotropin levels rise, hypothalamic sensitivity declines, until adult levels are reached and menarch ensues.

It usually takes about 2 - 3 years for cycles to become regular and all become ovulatory.

Hormonal Interactions During the Ovarian Cycle

GnRH released from hypothalamus stimulates FSH and LH release from anterior pituitary

FSH and LH stimulate follicle growth and estrogen secretion

Estrogen levels rise and feed back to anterior pituitary, inhibiting release (while stimulating production) of FSH and LH; in ovary, estrogen secretion is enhanced by maturation of follicles under the influence of FSH

Inhibin release by granulosa cells of follicle also inhibits FSH release

As estrogen levels peak (about midcycle), a burstlike release of accumulated LH (and FSH) from anterior pituitary stimulates secondary oocyte formation and ovulation; LH also transforms the ruptured follicle into a corpus luteum

Release of progesterone, estrogen and inhibin from corpus luteum inhibits release of FSH and LH from anterior pituitary

As LH blood levels decline, corpus luteum degenerates, and declining levels of progesterone and estrogen remove block to FSH and LH release; cycle begins again.

Uterine (Menstrual) Cycle

Cyclic changes occur in the uterine endometrium in response to ovarian hormones in blood

Menstrual phase (days 1-5): uterus sheds all but deepest layer of endometrium; detached tissue and blood pass out through vagina as menstrual flow

Proliferative phase (days 6-14): as estrogen blood levels rise, endometrium rebuilds itself

Ovulation occurs in ovary at end of this phase (day 14)

Secretory phase (days 15-28): increasing progesterone levels prepare endometrium for embryo implantation, creating blood vessels and stimulating nutrient secretion from uterine glands; also, cervical plug of mucus reforms to block further sperm entry

Extrauterine Effects of Estrogen and Progesterone

In addition to promotion of oogenesis and follicle growth in ovaries, estrogen also exerts anabolic effects on female reproductive tract (increasing size of the duct system in preparation for childbirth) and promotes appearance of secondary sex characteristics in female

Progesterone inhibits motility of uterus and promotes mammary gland activity.

Female Sexual Response

Erectile tissue in clitoris and breasts engorge with blood (similar to male response in penis), while increased activity of vestibular glands lubricates vestibule.

Orgasm is accompanied by increases in muscle tension, pulse rate, blood pressure, and release of oxytocin. Unlike males, females do not have a refractory period and so can have multiple organsms in a single sexual encounter. Males must ejaculate to achieve orgasm, which, when combined with the fact that females don't have to achieve orgasm ot concieve, increases chances for fertilization to occur.

Sexually Transmitted Diseases (STDs or Venereal Diseases (VDs): infectious diseases spread through sexual contact

Gonorrhea: caused by bacterium Neisseria gonorrheae

Syphilis: caused by bacterium Treponema pallidum

Chlamydia: caused by parasitic bacterium Chlamydia trachomatis

Genital Warts: caused by human papillomavirus (HPV) (certain types also cause invasive cervical cancer)

Genital Herpes: caused by human herpesviruses (herpes simplex virus)

Bacterial pathogens treated with antibiotics, while viral pathogens are generally treated with antiviral medications

Developmental Aspects of the Reproductive System:

Chronology of Sexual Development

Embryological and Fetal Events

Sex is determined by the sex chromosomes at conception; females have two X chromosomes and males have an X and a Y chromosome.

Sexual Differentiation of the Reproductive System

The gonads of both males and females begin to develop during week 5 of gestation.

During week 7 the gonads begin to become testes in males, and in week 8 they begin to form ovaries in females.

The external genitalia arise from the same structures in both sexes, with differentiation occurring in week 8.

About two months before birth the testes begin their descent toward the scrotum, dragging their nerve supply and blood supply with them.

Puberty: the period of life (between 10-15 years of age) when the reproductive organs grow to their adult size and become functional in response to gonadal hormones.

Menopause: the time of life in females (usually between 46-54 years of age) when menstruation (and ovulation) ceases

Gradual decline in estrogen levels causes the reproductive organs and breasts to atrophy, with many other possible effects

Hormone replacement therapy may be used to alleviate the signs and complications, but may increase risk of some hyperproliferative diseases (breast cancer)