membraneous

Testicle

[tes-ti-kuhl]

The testicle (from Latin testiculus , diminutive of testis, meaning "witness" [of virility], plural testes) is the male generative gland in animals. This article will concentrate on mammalian testicles unless otherwise noted.

The etymology of the word is somewhat colorfully based on Roman law. The aforementioned Latin word "testis", witness, was used in the firmly established legal principle "Testis unus, testis nullus" (one witness [equals] no witness), meaning that testimony by any one person in court was to be disregarded unless corroborated by the testimony of at least another. This led to the common practice of producing two witnesses, bribed to testify the same way in cases of lawsuits with ulterior motives. Since such "witnesses" always came in pairs, the meaning was accordingly extended, often in the diminutive (testiculus, testiculi).

Anatomy and physiology

Function

Like the ovaries (to which they are homologous), testicles are components of both the reproductive system (being gonads) and the endocrine system (being endocrine glands). The respective functions of the testicles are;

producing sperm (spermatozoa)
producing male sex hormones that of which testosterone is the best-known

Both functions of the testicle, sperm-forming and endocrine, are under control of gonadotropic hormones produced by the anterior pituitary:

luteinizing hormone (LH)
follicle-stimulating hormone (FSH)

External appearance

Male mammals have two testicles, which are often contained within an extension of the abdomen called the scrotum. In mammals with external testicles it is most common for one testis to hang lower than the other. It is estimated that in about 65% of men the lower hanging testicle is the Left (Owner's left) one. This is due to differences in the vascular anatomical structure on the right and left sides.

In healthy European adult human males, average testicular volume is 18cm³ per testis, with normal size ranging from 12cm³ to 30cm³. Measurement in the living adult is done in two basic ways:

comparing the testicle with ellipsoids of known sizes (orchidometer).
measuring the length, depth and width with a ruler, a pair of calipers or ultrasound imaging.

The volume is then calculated using the formula for the volume of an ellipsoid: 4/3 π × (length/2) × (width/2) × (depth/2).

To some extent, it is possible to change testicular size. Short of direct injury or subjecting them to adverse conditions, e.g., higher temperature than they are normally accustomed to, they can be shrunk by competing against their intrinsic hormonal function through the use of externally administered steroidal hormones. Steroids taken for muscle enhancement often have the undesired side effect of testicular shrinkage. Similarly, stimulation of testicular functions via gonadotropic-like hormones may enlarge their size. Testicles may shrink or atrophy during hormone replacement therapy.

Internal structure

Duct system

Under a tough membraneous shell, the tunica albuginea, the testis contains very fine coiled tubes called the seminiferous tubules. The tubes are lined with a layer of cells that, from puberty into old-age, produce sperm cells. The sperm travel from the seminiferous tubules to the rete testis located in the mediastinum testis, to the efferent ducts, and then to the epididymis where newly-created sperm cells mature (see spermatogenesis). The sperm move into the vas deferens, and are eventually expelled through the urethra and out of the urethral orifice through muscular contractions.

Between the seminiferous tubules are special cells called Leydig cells (or "interstitial cells") where testosterone and other androgens are formed.

Blood supply and lymphatic drainage

Blood supply and lymphatic drainage of the testes and scrotum are distinct:

The paired testicular arteries arise directly from the abdominal aorta and descend through the inguinal canal, while the scrotum and the rest of the external genitalia is supplied by the internal pudendal artery (itself a branch of the internal iliac artery).
The testis has collateral blood supply from 1. the cremasteric artery (a branch of the inferior epigastric artery, which is a branch of the external iliac artery), and 2. the vasal artery (a branch of the superior vesical artery, which is a branch of the internal iliac artery). Therefore, if the testicular artery is ligated, e.g., during a Fowler-Stevens orchiopexy for a high undescended testis, the testis will usually survive on these other blood supplies.
Lymphatic drainage of the testes follows the testicular arteries back to the paraaortic lymph nodes, while lymph from the scrotum drains to the inguinal lymph nodes.

Layers

Many anatomical features of the adult testis reflect its developmental origin in the abdomen.

The layers of tissue enclosing each testicle are derived from the layers of the anterior abdominal wall. Notably, the cremasteric muscle arises from the internal oblique muscle.

The blood-testis barrier

Large molecules cannot pass from the blood into the lumen of a seminiferous tubule due to the presence of tight junctions between adjacent Sertoli cells. The spermatogonia are in the basal compartment (deep to the level of the tight junctions) and the more mature forms such as primary and secondary spermatocytes and spermatids are in the adluminal compartment.

The function of the blood-testis barrier (red highlight in diagram above) may be to prevent an auto-immune reaction. Mature sperm (and their antigens) arise long after immune tolerance is established in infancy. Therefore, since sperm are antigenically different from self tissue, a male animal can react immunologically to his own sperm. In fact, he is capable of making antibodies against them.

Injection of sperm antigens causes inflammation of the testis (autoimmune orchitis) and reduced fertility. Thus, the blood-testis barrier may reduce the likelihood that sperm proteins will induce an immune response, reducing fertility and so progeny.

Temperature regulation

The testes work best at temperatures slightly less than core body temperature. The spermatogenesis is less efficient at lower and higher temperatures. There are a number of mechanisms to maintain the testes at the optimum temperature.

Cremasteric muscle

The cremasteric muscle is part of the spermatic cord. When this muscle contracts, the cord is shortened and the testicle is moved closer up toward the body, which provides slightly more warmth to maintain optimal testicular temperature. When cooling is required, the cremasteric muscle relaxes and the testicle is lowered away from the warm body and is able to cool. This phenomenon is known as the cremasteric reflex. It also occurs in response to stress (the testicles rise up toward the body in an effort to protect them in a fight). There are persistent reports that relaxation indicates approach of orgasm. There is a noticeable tendency to also retract during orgasm.

The testicles can also be lifted voluntarily using the pubococcygeus muscle, which partially activates related muscles. This can sometimes be triggered by tightening or sucking in the stomach or abdomen.

Development

There are two phases in which the testicles grow substantially, namely in embryonic and pubertal age.

Embryonic

During mammalian development, the gonads are at first capable of becoming either ovaries or testes. In humans, starting at about week 4 the gonadal rudiments are present within the intermediate mesoderm adjacent to the developing kidneys. At about week 6, sex cords develop within the forming testes. These are comprised of early Sertoli cells that surround and nurture the germ cells that migrate into the gonads shortly before sex determination begins. In males, the sex-specific gene SRY that is found on the Y-chromosome initiates sex determination by downstream regulation of sex-determining factors, (such as GATA4, SOX9 and AMH), which leads to development of the male phenotype, including directing development of the early bipotential gonad down the male path of development.

Pubertal

The testicles grow in response to the start of spermatogenesis. Size depends on lytic function, sperm production (amount of spermatogenisis present in testis), interstitial fluid, and Sertoli cell fluid production. After puberty, the volume of the testicles can be increased by over 500% as compared to the pre-pubertal size. In humans the average testicle size after puberty measures up to around 2 inches long, 0.8 inch in breadth, and 1.2 inches in height (5 x 2 x 3 cm). Testicles are fully descended before one reaches puberty.

Evolution

External testicles

The basal condition for mammals is to have internal testicles. Only the Boreoeutherian land mammals, the large group of mammals that includes humans, have externalized testicles. Indeed their testicles function best at temperatures lower than their core body temperature. Their testes are located outside of the body, suspended by the spermatic cord within the scrotum. The testes of the non-boreotherian mammals such as the monotremes, armadillos, sloths, elephants remain within the abdomen. There are also some Boreoeutherian mammals with internal testes, such as the rhinoceros.

Marine boreotherian mammals such as whales and dolphins, also have internal testes, but it has recently been shown (e.g., for dolphins) that they use elaborate vascular networks to provide the necessary temperature lowering for optimum function. As external testes would increase drag, many boreotherian aquatic mammals have internal testes which are kept cool by special circulatory systems that cool the arterial blood going to the testes by placing the arteries near veins bringing cooled venous blood from the skin.

There are several hypotheses why most boreotherian mammals have external testes which operate best at a temperature that is slightly less than the core body temperature, e.g. that it is stuck with enzymes evolved in a colder temperature due to external testes evolving for different reasons, that the lower temperature of the testes simply is more efficient for sperm production.

1) More efficient. The classic hypothesis is that cooler temperature of the testes allows for more efficient fertile spermatogenesis. In other words, there are no possible enzymes operating at normal core body temperature that are as efficient as the ones evolved, at least none appearing in our evolution so far.

The early mammals had lower body temperatures and thus their testes worked efficiently within their body. However it is argued that boreotherian mammals have higher body temperatures than the other mammals and had to develop external testicles to keep them cool. It is argued that those mammals with internal testicles, such as the monotremes, armadillos, sloths, elephants, and rhinoceroses, have a lower core body temperatures than those mammals with external testicles.

However, the question remains why birds despite having very high core body temperatures have internal testes and did not evolve external testes. It was once theorized that birds used their air sacs to cool the testes internally, but later studies revealed that birds' testes are able to function at core body temperature..

Some mammals which have seasonal breeding cycles keep their testes internal until the breeding season at which point their testes descend and increase in size and become external.

2) Irreversible adaptation to sperm competition. It has been suggested that the ancestor of the boreoeutherian mammals was a small mammal that required very large testes (perhaps rather like those of a hamster) for sperm competition and thus had to place its testes outside the body. This led to enzymes involved in spermatogenesis, spermatogenic DNA polymerase beta and recombinase activities evolving a unique temperature optimum, slightly less than core body temperature. When the boreoeutherian mammals then diversified into forms that were larger and/or did not require intense sperm competition they were stuck with enzymes that operated best at cooler temperatures and had to keep their testicles outside the body. This position is made less parsimonious by the fact that the kangaroo, a non-boreoeutherian mammal, has external testicles. The ancestors of kangaroos might, separately from boreotherian mammals, have also been subject to heavy sperm competition and thus developed external testes, however, kangaroo external testicles are suggestive of a possible adaptive function for external testes in large animals.

3) Protection from abdominal cavity pressure changes. One argument for the evolution of external testes is that it protects the testes from abdominal cavity pressure changes caused by jumping and galloping.

Testicular size

Testicular size as a proportion of body weight varies widely. In the mammalian kingdom, there is a tendency for testicular size to correspond with multiple mates (e.g., harems, polygamy). Production of testicular output sperm and spermatic fluid is also larger in polygamous animals, possibly a spermatogenic competition for survival. The testicles of the right whale are likely to be the largest of any animal, each weighing around 500 kg (1,100 lb).