Reproductive System

In mammals the sexes are separate organisms.  The human embryo will form 
both female and male structures which mature or disappear depending upon 
whether the individual is genetically male (XY) or female (XX).  As the 
gonads mature, they secrete hormones that direct the formation of 
secondary sex characteristics.

MALE Reproductive Anatomy and Histology

Testes

Paired oval male gonads, the testes, are located in the scrotal sac of 
most mammals.  Beneath the skin, two connective tissue layers, the tunica 
externa and the tunica albuginea surround the glands.  The testes are 
divided into lobules that house 1 - 3 seminiferous tubules.  Surrounding 
the outside of the seminiferous tubules are clusters of cells known as 
Sertoli, Leydig, or Interstitial cells.  These cuboidal cells are 
responsible for androgen production under the direction of GnRH from the 
Hypothalamus and LH from the AP.  Testosterone and its precursor DHEA, 
contribute to secondary sex characteristics.  Bone growth, muscle 
development, body hair patterns, laryngeal changes, and behavioral changes 
are seen with secretion of these androgens. 

Other cells in the seminiferous tubules are the sustentacular cells.  The 
sustentacular cells function in spermatogenesis to bind testosterone in 
the testes to allow for adequate hormone levels.  They also provide the 
blood-testes barrier to prevent immune cells from attacking the developing 
sperm.

The formation of sperm, called spermatogenesis, occurs in the seminiferous 
tubules and is stimulated by the  hormone FSH, secreted from the anterior 
pituitary.   Millions of sperm cells, spermatozoa, are produced in the 
testes.  This may occur because a population of spermatogonia retain, over 
many years, the ability to divide.  Spermatogonia (and their immediate 
progeny) divide by mitosis.  One of the daughter groups, the primary 
spermatocytes, then begins the process of meiosis.  Meiotic division 
creates 4 haploid cells in a two division cycle.  A primary spermatocyte 
divides (meiosis I and cytokinesis) to produce 2 secondary spermatocytes. 
Each of these divides again (meiosis II and cytokinesis) to produce 2 
spermatids. These haploid spermatid cells then mature into spermatozoa or 
sperm.  Final maturation and storage occurs in the epididymis.  300 
million sperm are produced daily and once they leave the male reproductive 
system, have a life expectancy of about 48 hours in the female 
reproductive system.  

Mature sperm or spermatozoa have a head, midpiece, and tail.  The head 
contains the condensed nucleus with a haploid set of chromosomes and a 
vesicle, called the acrosome, containing digestive enzymes that aid in 
penetrating layers surrounding the ovulated oocyte.  The midpiece contains 
mitochondria that produce energy in the form of ATP for the tail or 
flagellum.  Once activated by accessory gland secretions, the flagellum 
propels the sperm through the female reproductive tract.  *Male 
reproductive fertility assessment is based on number and viability of 
sperm, normal anatomy, and normal movement.

Activity:
Using the figures provided, examine a slide of a mammalian testis.  
Identify as many of the features and cell types as possible.

Duct System

Sperm are stored and mature in the tail of the epididymis.  During male 
climax, the smooth muscles within the ducts propel the sperm outward.  
From the epididymis, the sperm travel through the vas (ductus) deferens 
which is part of the spermatic cord.  The spermatic cord has a connective 
tissue covering that contains vessels, nerves, and ducts that aid and 
supply the male reproductive organs. The vas travels over the urinary 
bladder and around the ureters to the urethra.  As the vas joins with duct 
openings from accessory glands, the tube expands to form the ejaculatory 
duct.  The ejaculatory duct continues as the urethra.  In the male the 
urethra functions for sperm transport and urine transport, although not at 
the same time. The male urethra is 8 inches long and divided into three 
regions: the prostatic urethra that travels through the prostate, the 
membranous or penile urethra that travels through the body of the penis, 
and the spongy urethra that is surrounded by the spongy tissue of the 
glans penis. The urethra has a dilated portion, the ampulla, before it 
opens at the external urethral meatus.

Accessory Glands

The accessory glands of the male are the seminal vesicles, the prostate, 
and the bulbourethral (Cowper's) glands.  These glands secrete most of the 
liquid portion of the semen with the seminal vesicles producing 60% of the 
volume, the prostate producing about 20 % of the volume and the Cowper's 
glands producing 10% of the semen volume.

The seminal vesicles are paired structures that sit posterior to the 
urinary bladder and they join with the vas deferens to form the 
ejaculatory duct.  They produce an antibody and nutrient rich fluid 
containing sugars such as fructose.  The single prostate gland sits at the 
base of the urinary bladder and encloses the prostatic urethra. Their 
secretions aid in sperm motility.  The paired bulbourethral (Cowper's) 
glands lie at the bulb or root of the penis.  Their alkaline secretions 
help neutralize any acidic substances in the urethra, such as urine.  All 
accessory glands secrete an alkaline rich fluid to help neutralize the 
acidic pH of the female reproductive tract.  

External Genitalia
The external genitalia of the male are comprised of the scrotum and penis.  
The scrotum is a two compartment, connective tissue sac covered by skin 
and hair.  Each sac of the scrotum contains and supports one of the 
testes.  The scrotum allows the testes to be external from the abdominal 
cavity to allow for proper temperature maintenance, which is 3 degrees 
below normal body temperature. 
 
The penis is primarily connective tissue with an extensive blood supply.  
The gross regions are the root, shaft (body), and the glans.  The root and 
body are formed by three erectile tissues:    2 corpora cavernosa and 1 
corpora spongiosum.  The corpora spongiosum houses the urethra as it 
passes through the penis.  At the glans penis, only corpora spongiosum is 
present.  In the male climax, the blood supply in the penis changes.  
Arteries dilate, while veins constrict. This allows the connective tissue 
sinuses to fill with blood to create an erection to allow the penis to 
penetrate the female vagina and deliver semen into the female reproductive 
tract.  The glans penis is surrounded proximally by an extra fold of skin 
called the prepuce or foreskin.  
Activity:   
1] Using the figures provided, identify the structures (underlined terms) 
above.         
2] Using the semen anlaysis table, assess the abnormal results.
                                                                                                                     
Semen Analysis 
 
Subject X is a Caucasian male, age 32.  Subject and wife have not been 
successful in conceiving.  He requests an analysis of his semen.  His test 
results are given in the table below.  Reference ranges for the male 
population are also provided.

Test Requested	          Results for Mr X	Reference Range

ejaculate volume	    5 ml           	2-6 ml
viscosity and appearance    normal      	thick, opaque cream
sperm count	            22 million  	20 million / mL
morphology	            normal	        head, midpiece, flagella 
                                                 for 60%
motility	           75 % forward	        forward, linear for 50%
pH	                   7.5	                7 to 8
dead vs. alive	           82 % alive	        alive > 60%
WBC	                   0-1 / hpf	        1-3 cells/hp field
antisperm antibodies       negative	        negative IgG and IgA
Are the result values for Mr X within normal range for the tests 
performed?
 
Other patients present the following abnormal conditions.  Explain the 
possible causes for the following abnormal results : 
1) Low ejaculate volume
2) Watery, yellow appearance
3) Two heads with one tail, one head with no tail
4) Decreased motility, most circling
5) pH - 6.2
6) 5-8 WBC / high powered field
 


Section in figure provided:
Detail of wall of seminiferous tubule, showing stages of spermatogenesis. 
The large, vertically oriented nucleus at the base on the left belongs to 
a Sertoli cell; notice that sperm heads (somewhat out of focus) are 
clustered deep down near this nucleus. The horizontally flattened nuclei 
along the base of the tubule belong to spermatogonia, the continually 
multiplying, diploid germ cells. A few primary spermatocytes, with the 
dark, condensed chromosomes undergoing prophase of meiotic division, lie 
just above the spermatogonia. Above the spermatocytes are the round, 
relatively small, haploid spermatids, which would occupy the rest of the 
layers up toward the lumen.

Slide 47
Drawing of stages in the differentiation of sperm directly from 
spermatids. This process is called spermiogenesis. 
·	A = a still-rounded spermatid, with an acrosomal body beginning to 
form in the region of the Golgi apparatus. At the opposite pole of the 
nucleus lie the centrioles, one of which begins to spin out a long cilium 
(or flagellum). 
·	B = an elongating spermatid, with an acrosomal cap now forming 
over the top of the nucleus. The flagellum is longer and the centrioles 
are oriented perpendicular to each other. The centriole related to the 
flagellum is comparable to the basal body of ordinary cilia. 
·	C = further development of the acrosomal cap and beginning 
pinching off of excess cytoplasm, thanks to the formation of a filamentous 
manchette, nuclear ring, and annulus. 
·	D = further condensing of the nuclear chromosomal material and 
separating off of the excess cytoplasm. Notice that the intercellular 
bridge connecting this spermatid to its neighbor is still intact. 
E = the cytoplasmic mitochondria have now collected along the proximal 
portion of the flagellum and are thus conserved (for energy purposes) when 
the residual cytoplasm is cast off. The flagellum has meanwhile developed 
a complex fibrous sheath which surrounds a central core of microtubules 
arranged in the nine plus two arrangement typical of cilia.


FEMALE Reproductive Anatomy and Histology

Ovaries

The ovaries are paired gonads located inferior to the kidneys in the mid 
abdominal region, suspended by suspensory, ovarian, and broad ligaments 
and covered by a connective tissue capsule, the tunica albuginea.  The 
ovarian cortex contains ovarian follicles consists of developing immature 
eggs (oocytes) and surrounding cuboidal cells, thecal cells.  Ovaries 
produce gametes by a process called oogeneis.  They also produce hormones 
that target the uterus and other female tissues. 
In a meiotic process similar to that in the male, eggs are produced in the 
ovary and released into the oviducts where fertilization may occur.  In 
mammals, meiosis is not completed until a sperm activates the egg.  Due to 
unequal cytokinesis, however, only one haploid cell is produced.  This 
ensures that stored reserves of organelles and nutrients will be retained 
in one large (relative to the sperm) cell.

Early maturation of the oocyte occurs in a developing follicle.  The 
ovarian cycle is named for the events observe in the follicle triggered by 
response to gonadotropic hormones.

     Follicular Phase    ovarian follicles develop from primordial 
                          to Graafian follicle
                         regulated by FSH from the anterior pituitary
                         *follicle also functions as endocrine gl - 
                           secretes estogens

     Ovulation           Graafian follicle ruptures to release secondary oocyte
                         triggered by LH from AP 

     Luteal              formation of corpus luteum (CL) from remnant 
                          follicle cells
                         *follical now functions to secrete progestins 
                           and estrogens
                         regulated by LH

Activity:
Using the figures provided, observe the slides of a mammalian ovary and 
identify the features indicated. 

Duct System

The fallopian tubes (oviducts) develop separately from the ovaries.  At 
the lateral end of the tube, there are finger like extensions called 
fimbria that function to create vacuum like currents to retrieve the 
ovulated secondary oocytes.  The fimbria is supported by an enlarged 
trumpet shaped base called the infundibulum.  The infundibulum continues 
as the expanded portion of the tube called the ampulla and it is where 
fertilization takes place.  As the tube continues, its medial end is 
attached to the uterus at the isthmus. 

The uterus is a pear shaped structure in the pelvic region of the 
abdominal cavity suspended by the broad ligament. The external anatomy 
consists of the fundus, body, and neck or cervix.  The internal anatomy of 
the uterus is composed of three layers.  The internal epithelial lining is 
the endometrium and is a modified simple columnar epithelium in two 
layers, the basilar layer and the functional layer.  The muscle wall is 
the myometrium and is composed of smooth muscle.  The outer layer is a 
connective tissue layer called the perimetrium formed by the visceral 
peritoneum.  

The uterus can change size and shape during pregnancy (see figure).  The 
lining of the uterus will undergo several cycles known as the uterine 
cycle and relates to the hormones produced during the ovarian cycle.  The 
function of the uterus is to provide protection, support, and nutrition to 
the developing fetus and aid in delivery during labor.

    Proliferation (pre ovulatory)   basilar layer of endometrium replaces 
                                     functional layer
                                    triggered by estrogens from the ovary

    Secretory (post ovulatory)      functional layer secretes nutrients 
                                     for fertilized egg
                                    triggered by progestins and estrogens 
                                     from the ovary

    Menstrual (post luteal)         functional layer of endometrium lost 
                                    triggered by a dramatic drop in ovarian 
                                     hormones

The vagina is a muscular tube that connects the cervix of the uterus at 
the fornix.  The vagina functions as the female organ of copulation, serve 
as pathway for menstrual flow, and the birth canal.  The vaginal lining is 
stratified squamous and has an acidic pH to prevent overgrowth of 
bacteria.  A thin fold of tissue called the hymen partially closes the 
distal end of the vagina.  The vaginal orifice is the opening of the 
vagina in the vestibule enclosed by the labia.

External Genitalia
External Genitalia of the female is collectively termed the vulva or 
pudendum. The vulva consists of the:            
     clitoris         erectile tissue composed of corpora spongiosum
     labia majora     analogous to the male scrotum, contains sweat glands 
     labia minora     smaller skin fold that contains sebaceous glands
         both labia cover the vagina and urethra to help prevent drying   

Accessory Glands
     Lesser vestibular glands, Skene's glands - on either side of 
the urethral oriface; secrete mucus for vaginal lubrication.

     Greater vestibular glands, Bartholin's glands - on either side 
of the vaginal orifice; secrete mucus for vaginal lubrication.

     Mammary glands modified sweat glands of the skin that is functional in 
females;  Milk glandular alveoli develop in response to estrogens and
produce milk in response to AntPituitary - Prolactin (PRL) hormone
Milk release is under the control of the Post Pit - Oxytocin (OT)
                                    

Ovary slide seen in lab and in figure provided.
Maturing follicle, so called because it contains a definite antrum (or 
fluid-filled space) and many layers of granulosa cells. The egg is still a 
primary oocyte and sits to one side of the follicle on a mound of cells 
called the egg hillock or cumulus oophorus. The cells closest to the 
oocyte will be expelled with it at ovulation as the corona radiata. 
Surrounding the granulosa cells of the follicle is the theca interna, a 
rather cellular and vascular connective tissue layer, which secretes 
estrogen. Outside of this is the theca externa a more fibrous connective 
tissue layer, not well defined here. Several follicles may start 
to develop in any one monthly cycle, but in the human only one will 
mature, unless there are to be multiple ovulations and therefore possible 
multiple births. All follicles that don't complete their maturation 
undergo atresia (i.e., degenerate). The egg dies, the granulosa layer 
breaks up, and the whole follicle collapses and undergoes fibrotic change.


Ovarian Hormones and Cycle
The hormones from the thecal cells that line the follicles are:
DHEA is a hormone precursor to other reproductive hormones that control 
the ovarian and uterine cycles.
Follicle-Stimulating Hormone (FSH)
FSH is a heterodimer of 
·	the same alpha chain found in TSH (and LH) 
·	a beta chain of 115 amino acids, which gives it its unique 
properties.
Synthesis and release of FSH is triggered by the arrival from the 
hypothalamus of gonadotropin-releasing hormone (GnRH). The effect of FSH 
depends on one's sex.
 
FSH in females
In sexually-mature females, FSH (assisted by LH) acts on the follicle to 
stimulate it to release estrogens. 
FSH in males
In sexually-mature males, FSH acts on spermatogonia stimulating (with the 
aid of testosterone) the production of sperm. 
Luteinizing Hormone (LH)
LH is synthesized within the same pituitary cells as FSH and under the 
same stimulus (GnRH). It is a heterodimeric glycoprotein consisting of 
·	the same 89-amino acid alpha subunit found in FSH and TSH 
·	a beta chain of 115 amino acids that is responsible for its 
properties. The effects of LH also depend on sex. 
LH in females
In sexually-mature females, LH 
·	stimulates the follicle to secrete estrogen in the first half of 
the menstrual cycle 
·	a surge of LH triggers the completion of meiosis I of the egg and 
its release (ovulation) in the middle of the cycle 
·	stimulates the now-empty follicle to develop into the corpus 
luteum,which secretes progesterone during the latter half of the menstrual 
cycle.
        Estrogens                     estradial, estrone
        Progestins                    progesterone
        Androgens                     testosterone
Estrogens also function in creating secondary sex characteristics:  Fat 
deposition, breast development, hair distribution, skin changes, and bone 
development and will travel through lactiferous ducts to the lactiferous 
sinus and exit at the nipple.

Prolactin (PRL)
Prolactin is a protein of 198 amino acids. During pregnancy it helps in 
the preparation of the breasts for future milk production. After birth, 
prolactin promotes the synthesis of milk.