Testis

A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testosterone. Testosterone release is controlled by the anterior pituitary luteinizing hormone, whereas sperm production is controlled both by the anterior pituitary follicle-stimulating hormone and gonadal testosterone.

Structure

Appearance

Males have two testicles of similar size contained within the scrotum, which is an extension of the abdominal wall. Scrotal asymmetry, in which one testicle extends farther down into the scrotum than the other, is common. This is because of the differences in the vasculature's anatomy. For 85% of men, the right testis hangs lower than the left one.

Measurement and volume

The volume of the testicle can be estimated by palpating it and comparing it to ellipsoids of known sizes. Another method is to use calipers (an orchidometer) or a ruler either on the person or on an ultrasound image to obtain the three measurements of the x, y, and z axes (length, depth and width). These measurements can then be used to calculate the volume, using the formula for the volume of an ellipsoid:
:$Volume = \frac \cdot \pi \cdot \frac \cdot \frac \cdot \frac$
:$\approx length \cdot width \cdot depth \cdot 0.52$

However, the most accurate calculation of actual testicular volume is gained from the formula:

:$\approx length \cdot width \cdot depth \cdot 0.71$

An average adult testicle measures up to . The Tanner scale, which is used to assess the maturity of the male genitalia, assigns a maturity stage to the calculated volume ranging from stage I, a volume of less than 1.5 cm³; to stage V, a volume greater than 20 cm³. Normal volume is 15 to 25 cm³; the average is 18 cm³ per testis (range 12–30 cm³).

The number of spermatozoa an adult human male produces is directly proportional to testicular volume, as larger testicles contain more seminiferous tubules and Sertoli cells as a result. As such, men with larger testicles produce on average more sperm cells in each ejaculate, as testicular volume is positively correlated with semen profiles.

Internal structure

Duct system

The testes are covered by a tough fibrous shell called the tunica albuginea. Under the tunica albuginea, the testes contain very fine-coiled tubes called seminiferous tubules. The tubules are lined with a layer of cells ( germ cells) that develop from puberty through old age into sperm cells (also known as spermatozoa or male gametes). The developing sperm travel through 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 (spermatogenesis). The sperm move into the vas deferens, and are eventually expelled through the urethra and out of the urethral orifice through muscular contractions.

Primary cell types

Within the seminiferous tubules, the germ cells develop into spermatogonia, spermatocytes, spermatids and spermatozoa through the process of spermatogenesis. The gametes contain DNA for fertilization of an ovum Sertoli cellsthe true epithelium of the seminiferous epithelium, critical for the support of germ cell development into spermatozoa. Sertoli cells secrete inhibin. Peritubular myoid cells surround the seminiferous tubules.

Between tubules (interstitial cells) exist Leydig cellscells localized between seminiferous tubules that produce and secrete testosterone and other androgens important for puberty (including secondary sexual characteristics like facial hair), sexual behavior, and libido. Sertoli cells support spermatogenesis. Testosterone controls testicular volume.

Immature Leydig cells and interstitial macrophages and epithelial cells are also present.

Blood supply and lymphatic drainage

The testis has three sources of arterial blood supply: the testicular artery, the cremasteric artery, and the artery to the ductus deferens. 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 (a branch of the internal iliac artery).
* The testis has collateral blood supply from the cremasteric artery (a branch of the inferior epigastric artery, which is a branch of the external iliac artery), and the artery to the ductus deferens (a branch of the inferior 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. 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 occupy the basal compartment (deep to the level of the tight junctions) and the more mature forms, such as primary and secondary spermatocytes and spermatids, occupy the adluminal compartment.

The function of the blood–testis barrier may be to prevent an auto-immune reaction. Mature sperm (and their antigens) emerge significantly after immune tolerance is set in infancy. Since sperm are antigenically different from self-tissue, a male animal can react immunologically to his own sperm. The male can make antibodies against them.

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

Temperature regulation and responses

Spermatogenesis is enhanced at temperatures slightly less than core body temperature. The spermatogenesis is less efficient at lower and higher temperatures than 33 °C. Because the testes are located outside the body, the smooth tissue of the scrotum can move them closer or further away from the body. The temperature of the testes is maintained at 34.4 °C, a little below body temperature, as temperatures above 36.7 °C impede spermatogenesis. There are a number of mechanisms to maintain the testes at the optimum temperature.

The cremasteric muscle covers the testicles and the spermatic cord. When this muscle contracts, the cord shortens and the testicles move 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 testicles lower away from the warm body and are able to cool. Contraction also occurs in response to physical stress, such as blunt trauma; the testicles withdraw and the scrotum shrinks very close to the body in an effort to protect them.

The cremasteric reflex will reflexively raise the testicles. The testicles can also be lifted voluntarily using the pubococcygeus muscle, which partially activates related muscles.

Gene and protein expression

The human genome includes approximately 20,000 protein coding genes: 80% of these genes are expressed in adult testes. The testes have the highest fraction of tissue type-specific genes compared to other organs and tissues. About 1000 of them are highly specific for the testes, and about 2,200 show an elevated pattern of expression. A majority of these genes encode for proteins that are expressed in the seminiferous tubules and have functions related to spermatogenesis. Sperm cells express proteins that result in the development of flagella; these same proteins are expressed in the female in cells lining the Fallopian tube and cause the development of cilia. Sperm cell flagella and Fallopian tube cilia are homologous structures. The testis-specific proteins that show the highest level of expression are protamines.

Development

There are two phases in which the testes grow substantially. These are the embryonic and pubertal phases.
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 made up 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 lead to development of the male phenotype, including directing development of the early bipotential gonad toward the male path of development.

Testes follow the path of descent, from high in the posterior fetal abdomen to the inguinal ring and beyond to the inguinal canal and into the scrotum. In most cases (97% full-term, 70% preterm), both testes have descended by birth. In most other cases, only one testis fails to descend. This is called cryptorchidism. In most cases of cryptorchidism, the issue will mostly resolve itself within the first half year of life. However, if the testes do not descend far enough into the scrotum, surgical anchoring in the scrotum is required due to risks of infertility and testicular cancer.

The testes grow in response to the start of spermatogenesis. Size depends on lytic function, sperm production (amount of spermatogenesis present in testis), interstitial fluid, and Sertoli cell fluid production. The testicles are fully descended before the male reaches puberty.

Clinical significance

Protection and injury

* The testicles are very sensitive to impact and injury. The pain involved travels up from each testicle into the abdominal cavity, via the spermatic plexus, which is the primary nerve of each testicle. This will cause pain in the hip and the back. The pain usually fades within a few minutes.
* Testicular torsion is a medical emergency. This is because the longer it takes to access medical intervention with respect to extending ischemia, the higher the chance that the testicle will be lost. There is a 90% chance to save the testicle if de-torsion surgery is performed within six hours of testicular torsion onset.
* Testicular rupture is severe trauma affecting the tunica albuginea.
* Penetrating injuries to the scrotum may cause castration, or physical separation or destruction of the testes, possibly along with part or all of the penis, which results in total sterility if the testicles are not reattached quickly. In an effort to avoid severe infection, ample application of saline and bacitracin help remove debris and foreign objects from the wound.
* Jockstraps support and protect the testicles.

Diseases and conditions

* To improve the chances of catching cases of testicular cancer, other neoplasms, or other health issues early, regular testicular self-examination is recommended.
* Varicocele, swollen vein(s) from the testes, usually affecting the left side, the testis usually being normal.
* Hydrocele testis is swelling around testes caused by accumulation of clear liquid within a membranous sac, the testis usually being normal. It is the most common cause of scrotal swelling.
* Spermatocele is a retention cyst of a tubule of the rete testis or the head of the epididymis distended with barely watery fluid that contains spermatozoa.
* Endocrine disorders can also affect the size and function of the testis.
* Certain inherited conditions involving mutations in key developmental genes also impair testicular descent, resulting in abdominal or inguinal testes which remain nonfunctional and may become cancerous. Other genetic conditions can result in the loss of the Wolffian ducts and allow for the persistence of Müllerian ducts. Both excess and deficient levels of estrogens can disrupt spermatogenesis and cause infertility.
* Bell-clapper deformity is a deformity in which the testicle is not attached to the scrotal walls, and can rotate freely on the spermatic cord within the tunica vaginalis. Those with Bell-clapper are at a higher risk of testicular torsion.
* Orchitis is inflammation of the testicles
* Epididymitis is a painful inflammation of the epididymis or epididymides, frequently caused by bacterial infection but sometimes of unknown origin.
* Anorchia is the absence of one or both testicles.
* Cryptorchidism, or "undescended testicles", is when the testicle does not descend into the scrotum of an infant boy.
*Testicular enlargement is an unspecific sign of various testicular diseases, and can be defined as a testicular size of more than 5 cm ( long axis) × 3 cm (short axis).
* Blue balls is a condition concerning temporary fluid congestion in the testicles and prostate region, caused by prolonged sexual arousal.

Testicular prostheses are available to mimic the appearance and feel of one or both testicles, when absent as from injury or as treatment in association to gender dysphoria. There have also been some instances of their implantation in dogs.

Effects of exogenous hormones

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 (especially anabolic steroids) often have the undesired side effect of testicular shrinkage.

Stimulation of testicular functions via