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4.4: Testicular Reproductive System

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    91905
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    Learning Objectives

    • Describe the structure and function of the organs of the testicular reproductive system
    • Describe the structure and function of the sperm cell
    • Explain the events during spermatogenesis that produce haploid sperm from diploid cells
    • Identify the importance of testosterone in reproductive function

    4.4.1 Overview

    People often use the words "female" and "male" to describe two different concepts: our sense of gender identity, and our biological sex as determined by our X/Y chromosomes, hormones, sex organs, and other physical characteristics. For some people, gender identity is different from biological sex or their sex assigned at birth. In this chapter and the next chapter, "female" and "male" refer to sex only, and the typical reproductive anatomy of XX and XY individuals is discussed.

    Unique for its role in reproduction, a gamete is a specialized sex cell, which in humans carries 23 chromosomes—one half the number in body cells. In almost all sexually reproducing species, these two haploid cells differ in size; the smaller gamete is called the male gamete and the larger one is called the female gamete. At fertilization, the chromosomes in one male gamete, called a sperm (or spermatozoon), combine with the chromosomes in one female gamete, called an ovum. The function of the male, or testicular, reproductive system (Figure 4.4.1) is to produce sperm and transfer them to the female reproductive tract. The paired testes are a crucial component in this process, as they produce both sperm and androgens, the hormones that support male reproductive physiology. In male humans, the most important androgen is testosterone. For people with a penis, several accessory organs and ducts aid the process of sperm maturation and transport the sperm and other seminal components to the penis, which may deliver sperm to the female reproductive tract. In this section, we examine each of these different structures and discuss the process of sperm production and transport.51

    Testicular reproductive system structures

    Figure 4.4.1 Testicular Reproductive System - The structures of the testicular reproductive system include the testes, the epididymides, the penis, and the ducts and glands that produce and carry semen. Sperm exit the scrotum through the ductus deferens, which is bundled in the spermatic cord. The seminal vesicles and prostate gland add fluids to the sperm to create semen.
    Image Source:
    Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax

    4.4.2 Scrotum

    The testes are located in a skin-covered, highly pigmented, muscular sack called the scrotum that extends from the body behind the penis (Figure 4.10). This location is important in sperm production, which occurs within the testes and proceeds more efficiently when the testes are kept 2 to 4°C below core body temperature.

    The dartos muscle makes up the subcutaneous muscle layer of the scrotum (Figure 4.4.2). It continues internally to make up the scrotal septum, a wall that divides the scrotum into two compartments, each housing one testis. Descending from the internal oblique muscle of the abdominal wall are the two cremaster muscles, which cover each testis like a muscular net. By contracting simultaneously, the dartos and cremaster muscles can elevate the testes in cold weather (or water), moving the testes closer to the body and decreasing the surface area of the scrotum to retain heat. Alternatively, as the environmental temperature increases, the scrotum relaxes, moving the testes farther from the body core and increasing scrotal surface area, which promotes heat loss. Externally, the scrotum has a raised medial thickening on the surface called the raphae.52

    Anterior view of the structrues of the scrotum and testes.

    Figure 4.4.2 - This anterior view shows the structures of the scrotum and testes.
    Image Source: Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax.

    4.4.3 Testes

    The testes (singular = testis) are the male gonads—that is, the male reproductive organs. They produce both sperm and androgens, such as testosterone, and are active throughout the reproductive lifespan.

    Paired ovals, adult testes are each approximately 4 to 5 cm in length and are housed within the scrotum (Figure 4.4.3). They are surrounded by two distinct layers of protective connective tissue (Figure 4.12). The outer tunica vaginalis is a serous membrane that has both a parietal and a thin visceral layer. Beneath the tunica vaginalis is the tunica albuginea, a tough, white, dense connective tissue layer covering the testis itself. Not only does the tunica albuginea cover the outside of the testis, it also invaginates to form septa that divide the testis into 300 to 400 structures called lobules. Within the lobules, sperm develop in structures called seminiferous tubules. During the seventh month of the developmental period of a male fetus, each testis moves through the abdominal musculature to descend into the scrotal cavity. This is called the “descent of the testis.” Cryptorchidism is the clinical term used when one or both of the testes fail to descend into the scrotum before birth.53

    A cross section of the testis with anatomy labeled.

    Figure 4.4.3 Anatomy of the Testis - This sagittal view shows the seminiferous tubules, the site of sperm production. Formed sperm are transferred to the epididymis, where they mature. They leave the epididymis during an ejaculation via the ductus deferens.
    Image Source: Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013. This work is distributed under a CC BY 4.0 license. Available from Open Stax

    The tightly coiled seminiferous tubules form the bulk of each testis. They are composed of developing sperm cells surrounding a lumen, the hollow center of the tubule, where formed sperm are released into the duct system of the testis. Specifically, from the lumens of the seminiferous tubules, sperm move into the straight tubules (or tubuli recti), and from there into a fine meshwork of tubules called the rete testes. Sperm leave the rete testes, and the testis itself, through the 15 to 20 efferent ductules that cross the tunica albuginea.54

    Inside the seminiferous tubules are six different cell types. These include supporting cells called sustentacular cells, as well as five types of developing sperm cells called germ cells. Germ cell development progresses from the basement membrane—at the perimeter of the tubule—toward the lumen. Let’s look more closely at these cell types.

    4.4.3.1 Sertoli Cells

    Surrounding all stages of the developing sperm cells are elongate, branching Sertoli cells. Sertoli cells are a type of supporting cell called a sustentacular cell, or sustentocyte, typically found in epithelial tissue. Sertoli cells secrete signaling molecules that promote sperm production and can control whether germ cells live or die. They extend physically around the germ cells from the peripheral basement membrane of the seminiferous tubules to the lumen. Tight junctions between these sustentacular cells create the blood–testis barrier, which keeps blood-borne substances from reaching the germ cells and, at the same time, keeps surface antigens on developing germ cells from escaping into the bloodstream and prompting an autoimmune response.

    4.4.3.2 Germ Cells

    The least mature cells, the spermatogonia (singular = spermatogonium), line the basement membrane inside the tubule. Spermatogonia are the stem cells of the testis, which means that they are still able to differentiate into a variety of different cell types throughout adulthood. Spermatogonia divide to produce primary and secondary spermatocytes, then spermatids, which finally produce formed sperm. The process that begins with spermatogonia and concludes with sperm production is called spermatogenesis.

    4.4.3.3 SpermatogenesisEdit section

    As just noted, spermatogenesis occurs in the seminiferous tubules that form the bulk of each testis (Figure 4.4.3). The process begins at puberty, after which time sperm are produced constantly throughout a male's life. One production cycle, from spermatogonia through formed sperm, takes approximately 64 days. A new cycle starts approximately every 16 days, although this timing is not synchronous across the seminiferous tubules. Sperm counts—the total number of sperm a person produces—slowly decline after age 35, and some studies suggest that smoking can lower sperm counts irrespective of age.55

    The process of spermatogenesis begins with mitosis of the diploid spermatogonia (Figure 4.4.4). Because these cells are diploid (2n), they each have a complete copy of the person's genetic material, or 46 chromosomes. However, mature gametes are haploid (1n), containing 23 chromosomes—meaning that daughter cells of spermatogonia must undergo a second cellular division through the process of meiosis.

    Mitosis of a spermatogonial stem cell.

    Figure 4.4.4 Spermatogenesis - (a) Mitosis of a spermatogonial stem cell involves a single cell division that results in two identical, diploid daughter cells (spermatogonia to primary spermatocyte). Meiosis has two rounds of cell division: primary spermatocyte to secondary spermatocyte, and then secondary spermatocyte to spermatid. This produces four haploid daughter cells (spermatids). (b) In this electron micrograph of a cross-section of a seminiferous tubule from a rat, the lumen is the light-shaded area in the center of the image. The location of the primary spermatocytes is near the basement membrane, and the early spermatids are approaching the lumen (tissue source: rat). EM × 900. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)
    Image Source: Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax.

    Two identical diploid cells result from spermatogonia mitosis. One of these cells remains a spermatogonium, and the other becomes a primary spermatocyte, the next stage in the process of spermatogenesis. As in mitosis, DNA is replicated in a primary spermatocyte, before it undergoes a cell division called meiosis I. During meiosis I, each of the 23 pairs of chromosomes separates. This results in two cells, called secondary spermatocytes, each with only half the number of chromosomes. Now, a second round of cell division (meiosis II) occurs in both secondary spermatocytes. During meiosis II each of the 23 replicated chromosomes divides, similar to what happens during mitosis. Thus, meiosis results in separating the chromosome pairs. This second meiotic division results in a total of four cells with only half of the number of chromosomes. Each of these new cells is a spermatid. Although haploid, early spermatids look very similar to cells in the earlier stages of spermatogenesis, with a round shape, central nucleus, and large amount of cytoplasm. A process called spermiogenesis transforms these early spermatids, reducing the cytoplasm, and beginning the formation of the parts of a true sperm. The fifth stage of germ cell formation—spermatozoa, or formed sperm—is the end result of this process, which occurs in the portion of the tubule nearest the lumen. Eventually, the sperm are released into the lumen and are moved along a series of ducts in the testis toward a structure called the epididymis for the next step of sperm maturation.

    4.4.4 Structure of Formed Sperm

    Sperm are smaller than most cells in the body; in fact, the volume of a sperm cell is 85,000 times less than that of the female gamete. Approximately 100 to 300 million sperm are produced each day, whereas females typically ovulate only one oocyte per month. As is true for most cells in the body, the structure of sperm cells speaks to their function. Sperm have a distinctive head, mid-piece, and tail region (Figure 4.4.5). The head of the sperm contains the extremely compact haploid nucleus with very little cytoplasm. These qualities contribute to the overall small size of the sperm (the head is only 5 μm long). A structure called the acrosome covers most of the head of the sperm cell as a “cap” filled with lysosomal enzymes important for preparing sperm to participate in fertilization. Tightly packed mitochondria fill the mid-piece of the sperm. ATP produced by these mitochondria will power the flagellum, which extends from the neck and the mid-piece through the tail of the sperm, enabling it to move the entire sperm cell. The central strand of the flagellum, the axial filament, is formed from one centriole inside the maturing sperm cell during the final stages of spermatogenesis.56

    Structure of sperm.

    Figure 4.4.5 Structure of Sperm - Sperm cells are divided into a head, containing DNA; a mid-piece, containing mitochondria; and a tail, providing motility. The acrosome is oval and somewhat flattened.
    Image Source:
    Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax

    4.4.5 Sperm Transport

    To fertilize an egg without medical intervention, sperm must be moved from the seminiferous tubules in the testes, through the epididymis, and—later during ejaculation—along the length of the penis and out into the female reproductive tract.

    4.4.5.1 Role of the EpididymisEdit section

    From the lumen of the seminiferous tubules, the immotile sperm are surrounded by testicular fluid and moved to the epididymis (plural = epididymides), a coiled tube attached to the testis where newly formed sperm continue to mature (Figure 4.4.4). Though the epididymis does not take up much room in its tightly coiled state, it would be approximately 6 m (20 feet) long if straightened. It takes an average of 12 days for sperm to move through the coils of the epididymis, with the shortest recorded transit time in humans being one day. Sperm enter the head of the epididymis and are moved along predominantly by the contraction of smooth muscles lining the epididymal tubes. As they are moved along the length of the epididymis, the sperm further mature and acquire the ability to move under their own power. Once inside the female reproductive tract, they will use this ability to move independently toward the unfertilized egg. The more mature sperm are then stored in the tail of the epididymis (the final section) until ejaculation occurs.57

    4.4.5.2 Duct SystemEdit section

    During ejaculation, sperm exit the tail of the epididymis and are pushed by smooth muscle contraction to the ductus deferens (also called the vas deferens). The ductus deferens is a thick, muscular tube bundled together inside the scrotum with connective tissue, blood vessels, and nerves into a structure called the spermatic cord (Figure 4.4.2 & 4.4.3). Because the ductus deferens is physically accessible within the scrotum, surgical sterilization to interrupt sperm delivery can be performed by cutting and sealing a small section of the ductus (vas) deferens. This procedure is called a vasectomy, and it is an effective form of birth control. Although it may be possible to reverse a vasectomy, clinicians consider the procedure permanent, and advise people to undergo it only if they are certain they no longer wish to have children.

    From each epididymis, each ductus deferens extends superiorly into the abdominal cavity through the inguinal canal in the abdominal wall. From here, the ductus deferens continues posteriorly to the pelvic cavity, ending posterior to the bladder where it dilates in a region called the ampulla (meaning “flask”).

    Sperm make up only 5 percent of the final volume of semen, the thick, milky fluid that is ejaculated. The bulk of semen is produced by three critical accessory glands of the male reproductive system: the seminal vesicles, the prostate, and the bulbourethral glands.

    4.4.5.3 Seminal VesiclesEdit section

    As sperm pass through the ampulla of the ductus deferens at ejaculation, they mix with fluid from the associated seminal vesicle (Figure 4.4.2). The paired seminal vesicles are glands that contribute approximately 60 percent of the semen volume. Seminal vesicle fluid contains large amounts of fructose, which is used by the sperm mitochondria to generate ATP to allow movement through the female reproductive tract.

    The fluid, now containing both sperm and seminal vesicle secretions, next moves into the associated ejaculatory duct, a short structure formed from the ampulla of the ductus deferens and the duct of the seminal vesicle. The paired ejaculatory ducts transport the seminal fluid into the next structure, the prostate gland.58

    4.4.5.4 Prostate GlandEdit section

    The centrally located prostate gland sits anterior to the rectum at the base of the bladder surrounding the prostatic urethra (the portion of the urethra that runs within the prostate, (Figure 4.4.6).

    Lateral and transverse view of the flaccid and erect penis.

    Figure 4.4.6 Cross-Sectional Anatomy of the Penis - Three columns of erectile tissue make up most of the volume of the penis.
    Image Source:
    Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax

    About the size of a walnut, the prostate is formed of both muscular and glandular tissues. It excretes an alkaline, milky fluid to the passing seminal fluid—now called semen—that is critical to first coagulate and then decoagulate the semen following ejaculation. The temporary thickening of semen helps retain it within the female reproductive tract, providing time for sperm to utilize the fructose provided by seminal vesicle secretions. When the semen regains its fluid state, sperm can then pass farther into the female reproductive tract. The prostate normally doubles in size during puberty. At approximately age 25, it gradually begins to enlarge again.

    4.4.5.5 Bulbourethral GlandsEdit section

    The final addition to semen is made by two bulbourethral glands (or Cowper’s glands) that release a thick, salty fluid that lubricates the end of the urethra and the vagina and helps to clean urine residues from the penile urethra. The fluid from these accessory glands is released after the male becomes sexually aroused, and shortly before the release of the semen. It is, therefore, sometimes called pre-ejaculate. It is important to note that, in addition to the lubricating proteins, it is possible for bulbourethral fluid to pick up sperm already present in the urethra, and therefore it may be able to cause pregnancy.

    4.4.6 The Penis

    The penis is the male organ of copulation (sexual intercourse). It is flaccid for non-sexual actions, such as urination, and turgid and rod-like with sexual arousal. When erect, the stiffness of the organ allows it to penetrate into the vagina and deposit semen into the female reproductive tract.59

    The shaft of the penis surrounds the urethra (Figure 4.4.6). The shaft is composed of three column-like chambers of erectile tissue that span the length of the shaft. Each of the two larger lateral chambers is called a corpus cavernosum (plural = corpora cavernosa). Together, these make up the bulk of the penis. The corpus spongiosum, which can be felt as a raised ridge on the erect penis, is a smaller chamber that surrounds the spongy, or penile, urethra. The end of the penis, called the glans penis, has a high concentration of nerve endings, resulting in very sensitive skin that influences the likelihood of ejaculation (Figure 4.4.3). The skin from the shaft extends down over the glans and forms a collar called the prepuce (or foreskin). The foreskin also contains a dense concentration of nerve endings, and both lubricate and protect the sensitive skin of the glans penis. A surgical procedure called circumcision, often performed for religious or social reasons, removes the prepuce, typically within days of birth.

    Both sexual arousal and REM sleep (during which dreaming occurs) can induce an erection. Penile erections are the result of vasocongestion, or engorgement of the tissues because of more arterial blood flowing into the penis than is leaving in the veins. During sexual arousal, nitric oxide (NO) is released from nerve endings near blood vessels within the corpora cavernosa and spongiosum. Release of NO activates a signaling pathway that results in relaxation of the smooth muscles that surround the penile arteries, causing them to dilate. This dilation increases the amount of blood that can enter the penis and induces the endothelial cells in the penile arterial walls to also secrete NO and perpetuate the vasodilation. The rapid increase in blood volume fills the erectile chambers, and the increased pressure of the filled chambers compresses the thin-walled penile venules, preventing venous drainage of the penis. The result of this increased blood flow to the penis and reduced blood return from the penis is erection. Depending on the flaccid dimensions of a penis, it can increase in size slightly or greatly during erection, with the average length of an erect penis measuring approximately 15 cm.60

    4.4.7 TestosteroneEdit section

    Testosterone, an androgen, is a steroid hormone produced by Leydig cells. The alternate term for Leydig cells, interstitial cells, reflects their location between the seminiferous tubules in the testes. In male embryos, testosterone is secreted by Leydig cells by the seventh week of development, with peak concentrations reached in the second trimester. This early release of testosterone results in the anatomical differentiation of the male sexual organs. In childhood, testosterone concentrations are low. They increase during puberty, activating characteristic physical changes and initiating spermatogenesis.

    4.4.7.1 Functions of TestosteroneEdit section

    The continued presence of testosterone is necessary to keep the male reproductive system working properly, and Leydig cells produce approximately 6 to 7 mg of testosterone per day. Testicular steroidogenesis (the manufacture of androgens, including testosterone) results in testosterone concentrations that are 100 times higher in the testes than in the circulation. Maintaining these normal concentrations of testosterone promotes spermatogenesis, whereas low levels of testosterone can lead to infertility. In addition to intratesticular secretion, testosterone is also released into the systemic circulation and plays an important role in muscle development, bone growth, the development of secondary sex characteristics, and maintaining libido (sex drive) in both males and females. In females, the ovaries secrete small amounts of testosterone, although most is converted to estradiol. A small amount of testosterone is also secreted by the adrenal glands in both sexes.

    The regulation of testosterone concentrations throughout the body is critical for male reproductive function (Figure 4.4.7).61

    Regulation of testosterone production: 1) Hypothalamus releases GnRH. GnRH stimulates the anterior pituitary to release FSH and LH. 2) LH stimulates the Leydig cells to release testosterone. FSH stimulates the Sertoli cells to release ABP. ABP binds to testosterone, keeping the latter at a high concentration. 3) Inhibin negatively feeds back to anterior pituitary, inhibiting further release of FSH. Testosterone negatively feeds back to the hypothalamus and pituitary, inhibiting further release of GnRH, FSH, and LH.

    Figure 4.4.7 Regulation of Testosterone Production - The hypothalamus and pituitary gland regulate the production of testosterone and the cells that assist in spermatogenesis. GnRH activates the anterior pituitary to produce LH and FSH, which in turn stimulate Leydig cells and Sertoli cells, respectively. The system is a negative feedback loop because the end products of the pathway, testosterone and inhibin, interact with the activity of GnRH to inhibit their own production.
    Image Source:
    Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax

    The regulation of Leydig cell production of testosterone begins outside of the testes. The hypothalamus and the pituitary gland in the brain integrate external and internal signals to control testosterone synthesis and secretion. The regulation begins in the hypothalamus. Pulsatile release of a hormone called gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the endocrine release of hormones from the pituitary gland. Binding of GnRH to its receptors on the anterior pituitary gland stimulates release of the two gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These two hormones are critical for reproductive function in all humans. In the testes, FSH binds predominantly to the Sertoli cells within the seminiferous tubules to promote spermatogenesis. FSH also stimulates the Sertoli cells to produce hormones called inhibins, which function to inhibit FSH release from the pituitary, thus reducing testosterone secretion. These polypeptide hormones correlate directly with Sertoli cell function and sperm number; inhibin B can be used as a marker of spermatogenic activity. LH binds to receptors on Leydig cells in the testes and upregulates the production of testosterone.62

    A negative feedback loop predominantly controls the synthesis and secretion of both FSH and LH. Low blood concentrations of testosterone stimulate the hypothalamic release of GnRH. GnRH then stimulates the anterior pituitary to secrete LH into the bloodstream. In the testis, LH binds to LH receptors on Leydig cells and stimulates the release of testosterone. When concentrations of testosterone in the blood reach a critical threshold, testosterone itself will bind to androgen receptors on both the hypothalamus and the anterior pituitary, inhibiting the synthesis and secretion of GnRH and LH, respectively. When the blood concentrations of testosterone once again decline, testosterone no longer interacts with the receptors to the same degree and GnRH and LH are once again secreted, stimulating more testosterone production. This same process occurs with FSH and inhibin to control spermatogenesis.

    Student Contribution

    Summary for Male Birth Control Summary
    Amira, Isabel, and Caroline

    Male vs. Female

    The responsibility of contraception has largely fallen on female partners. Compared to the multitude of female hormonal birth control options, there is currently no hormonal male birth control on the market. This widening disparity in gender equality, equitable views, and double standard in biomedical research on male birth control could be hindering its advancement (ChoGlueck 2022, Jacobstein et al. 2023, Nguyen and Jacobsohn, 2023).

    Vasalgel

    A non-hormonal male long acting reversible contraction (LARC) in development is Vasalgel. The product is injected into the vas deferens and precipitates to block flow of sperm (Khourdaji et al, 2018). Clinical trials on rabbits and monkeys showed that Vasalgel was effective in preventing pregnancy for up to 2 years, and once it is flushed out of the vas deferens with sodium bicarbonate, sperm can flow again (Colagross-Schouten et al, 2018; Waller et al, 2017). However, further testing and sperm analysis must be done for Vasalgel to be available as a male LARC for the general population.

    Testosterone

    There are also hormonal methods in development. In clinical trials, administration of testosterone and progestin has shown to effectively suppress spermatogenesis. While most studies are on testosterone injections, research is underway for a self-administered transdermal gel option (Amory et al, 2023). While these hormonal methods have proven to be effective, they are not widely available due to uncomfortable side effects such as acne, mood changes, headaches, and night sweats (Ilani et al, 2011).

    Anti-fertility Vaccines

    A variety of anti-fertility vaccines have been under development, targeting specific hormones that play a role in gamete production. Talwar and Raghupathy (1989) discussed the developments of a single injection procedure for sterilization or castration of male animals. The injection consists of Bacillus Calmette-Guerin, a vaccine widely used for tuberculosis disease, as it can degenerate the blood-testis barrier and induce the production of anti-sperm antibodies. This leads either to reversible blockage of spermatogenesis or permanent destruction of Leydig cells depending on whether it is injected in uniform concentrations or a single high-concentrated shot, respectively. Success rate of the procedure is promising, showing signs of full effectiveness on
    mammals with temporary inflammation at the site of injection being the only side effect (Talwar & Raghupathy 1989). They have also been testing vaccines inducing antibodies against human chorionic gonadotropin, causing degeneration of the tubules as well as Lumen cells. The procedure resulted in decline of testosterone leves, size of testicles and an overall hindrance to spermatogenesis. (Talwar & Raghupathy 1989). Bao et al.(2019) suggests a procedure where four reagents are injected simultaneously and, depending on the ratio of each, could induce “physical clogging of the vas deferens and chemical inhibition of the sperm motility.” The method also promises a short and simple approach to reverse the effects in a procedure that wouldn’t need a clinical setting. This
    serum is still undergoing trials, as the study examines further research to be done including “verifying the safety of materials” through more animal experiments and analysis of long term side effects.

    Heat-Based Methods

    Another effective method being tested is the use of temperature regulation to “reverse” spermatogenesis through germ cell apostasis(Liu, 2010). Since
    spermatogenesis is known to take place in specific temperature conditions, where the scortum is lower than the core body temperature, trials showed that increasing testicular temperature or heat exposure would cause germinal epitherlium damage, suppressing the gamete production process as well as the amount of sperm output(Liu, 2010). As mentioned by Kandeel and Swerdloff (1988), depending on the amount of heat, a small amount would damage mainly primary spermatocytes and a larger exposure would destroy spermatids. A side effect recorded was “raising the temperature in the testis to
    values above the minimal effective exposure (42 to 43°C in most species) may carry a risk of a permanent testicular injury” (Kandeel & Swerdloff, 1988).

    Male Willingness

    Surveys taken in the 1970s vs the 1990s show an increase in male willingness to take hormonal contraception (Balswik 1972, Martin et al. 2000). Women’s views similarly reflect this interest in a male birth control pill, with a 2020 survey showing 69.7% in favor of male contraception (Richard et al. 2022). This general support of male birth control suggests further development of a male birth control pill is necessary.

    References

    Amory, J. K., Blithe, D. L., Sitruk-Ware, R., Swerdloff, R. S., Bremner, W. J., Dart, C., ... & Wang, C. (2023). Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone). Contraception, 110064.

    Bao, W., Xie, L., Zeng, X., Kang, H., Wen, S., Cui, B., Li, W., Qian, Y., Wu, J., Li, T., Deng, K., Xin, H.-B., & Wang, X. (2019). A Cocktail-Inspired Male Birth Control Strategy with Physical/Chemical Dual Contraceptive Effects and Remote Self-Cleared Properties. ACS Nano, 13(2), 1003–1011. https://doi.org/10.1021/acsnano.8b06683.

    Balswick, J. O. (1972). Attitudes of lower class males toward taking a male birth control pill. Family Coordinator, 195-199.

    ChoGlueck C. (2022). Still no pill for men? Double standards & demarcating values in biomedical research. Studies in history and philosophy of science, 91, 66–76. https://doi.org/10.1016/j.shpsa.2021.11.010

    Colagross-Schouten, A., Lemoy, M. J., Keesler, R. I., Lissner, E., & VandeVoort, C. A. (2017). The contraceptive efficacy of intravas injection of Vasalgel™ for adult male rhesus monkeys. Basic and clinical andrology, 27(1), 1-7.

    Ilani, N., Swerdloff, R. S., & Wang, C. (2011). Male hormonal contraception: potential risks and benefits. Reviews in endocrine & metabolic disorders, 12(2), 107–117. 

    Kandeel, F. R., & Swerdloff, R. S. (1988). Role of temperature in regulation of spermatogenesis and the use of heating as a method for contraception. Fertility and sterility, 49(1), 1–23. https://doi.org/10.1016/s0015-0282(16)59640-x

    Khourdaji, I., Zillioux, J., Eisenfrats, K., Foley, D., & Smith, R. (2018). The future of male contraception: a fertile ground. Translational andrology and urology, 7(Suppl 2), S220.

    Jacobstein, R., Radloff, S., Khan, F., Mimno, K., Pal, M., Snell, J., Stafford, R., Touré, C., & Tripathi, V. (2023). Down But Not Out: Vasectomy Is Faring Poorly Almost Everywhere—We Can Do Better To Make It A True Method Option. Global Health: Science and Practice, 11(1), e2200369. https://doi.org/10.9745/GHSP-D-22-00369

    Liu Y. X. (2010). Temperature control of spermatogenesis and prospect of male contraception. Frontiers in bioscience (Scholar edition), 2(2), 730–755. https://doi.org/10.2741/s97

    Martin, C. W., Anderson, R. A., Cheng, L., Ho, P. C., van der Spuy, Z., Smith, K. B., Glasier, A. F., Everington, D., & Baird, D. T. (2000). Potential impact of hormonal male contraception: Crosscultural implications for development of novel preparations. HUMAN REPRODUCTION, 15(3), 637–645. https://doi.org/10.1093/humrep/15.3.637

    Nguyen, B. T., & Jacobsohn, T. L. (2023). Men’s willingness to use novel male contraception is linked to gender-equitable attitudes: Results from an exploratory online survey☆,☆☆. CONTRACEPTION, 123, 110001. https://doi.org/10.1016/j.contraception.2023.110001

    Richard, C., Pourchasse, M., Freton, L., Esvan, M., Ravel, C., Peyronnet, B., Mathieu, R., & Chhor, S. (2022). Male contraception: What do women think? PROGRES EN UROLOGIE, 32(4), 276–283. https://doi.org/10.1016/j.purol.2021.11.003

    Shih, G., Turok, D. K., & Parker, W. J. (2011). Vasectomy: the other (better) form of sterilization. Contraception, 83(4), 310-315.
    Sokal, D., McMULLEN, S. U. S. A. N., GATES, D., DOMINIK, R., & Male Sterilization Investigator Team. (1999). A comparative study of the no scalpel and standard incision approaches to vasectomy in 5 countries. The Journal of urology, 162(5), 1621-1625.

    Talwar, G. P., & Raghupathy, R. (1989). Anti-fertility vaccines. Vaccine, 7(2), 97–101. https://doi.org/10.1016/0264-410x(89)90043-1
    Waller, D., Bolick, D., Lissner, E., Premanandan, C., & Gamerman, G. (2017). Reversibility of Vasalgel™ male contraceptive in a rabbit model. Basic and clinical andrology, 27, 1-9.

    Full text of this article can be found in Chapter 11.4, Student Contributions.

    Glossary Terms

    Androgens
    Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.
    Cremaster muscles
    Muscles forming the ABDOMINAL WALL including RECTUS ABDOMINIS; ABDOMINAL OBLIQUE MUSCLES, transversus abdominis, pyramidalis muscles and quadratus abdominis
    Cytoplasm
    The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES
    Dartos muslce
    the scrotal part of the dartos fascia, composed by smooth cells
    Ejaculation
    The emission of SEMEN to the exterior, resulting from the contraction of muscles surrounding the male internal urogenital ducts
    Flagella
    A whiplike motility appendage present on the surface cells. Prokaryote flagella are composed of a protein called FLAGELLIN. Bacteria can have a single flagellum, a tuft at one pole, or multiple flagella covering the entire surface. In eukaryotes, flagella are threadlike protoplasmic extensions used to propel flagellates and sperm. Flagella have the same basic structure as CILIA but are longer in proportion to the cell bearing them and present in much smaller numbers
    Gamete
    haploid reproductive cell that contributes genetic material to form an offspring
    Luman
    term that describes the cavity within the tubular structure. It usually refers to the space inside digestive, respiratory, and urogenital organs or vessels of the body
    Mitochondria
    cellular organelles bound by a double lipid bilayer that function primarily in the production of cellular energy (ATP)
    Oocyte
    A cell that results from the division of the oogonium and undergoes meiosis I at the LH surge and meiosis II at fertilization to become a haploid ovum.
    Ovum
    A haploid female gamete resulting from completion of meiosis II at fertilization.
    Scrotum
    The external pouch of skin and muscle that houses the testes.
    Sperm
    (also, spermatozoon) The male gamete.
    Testes
    The testes (singular = testis) are the male gonads—that is, the male reproductive organs. They produce both sperm and androgens, such as testosterone, and are active throughout the reproductive lifespan.
    Testosterone
    A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL
    Tunica albuginea
    The fibrous envelope that extends the length of the corpus cavernosum penis and corpus spongiosum penis. It is a bi-layered
    Tunica vaginalis
    A closed peritoneal sac surrounding the front and sides of the testis and extends upwards over the spermatic cord
    Vas deferens
    The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct.

    Footnotes

    1. Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax
    2. Betts et al, 2013

    3. Betts et al, 2013
    4. Betts et al, 2013
    5. Betts et al, 2013
    6. Betts et al, 2013
    7. Betts et al, 2013
    8. Betts et al, 2013
    9. Betts et al, 2013
    10. Betts et al, 2013
    11. Betts et al, 2013
    12. Betts et al, 2013

    Image Acknowledgements

    Betts, J. Gordon, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix. Anatomy and Physiology. (2013). Open Stax, 2013 This work is distributed under a CC BY 4.0 license. Available from Open Stax


    4.4: Testicular Reproductive System is shared under a CC BY 4.0 license and was authored, remixed, and/or curated by LibreTexts.

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