1 CONTACT Jennifer Koziol jkoziol@ttu.edu © 2023 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http:// creativecommons.org/licenses/by-nc/4.0/), permitting all noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Citation line: Clinical Theriogenology 2023, 15, 9271, http://dx.doi.org/10.58292/CT.v15.9271 Review Report Pathophysiology, diagnosis, and management of testicular degeneration in the bull Jennifer Koziol,a Colin Palmerb aTexas Tech School of Veterinary Medicine, Amarillo, USA bWestern College of Veterinary Medicine, Saskatoon, SK, Canada Abstract Testicular degeneration in the bull is described as diffuse disintegration of seminiferous tubule structure and function causing a profound reduction in sperm concentration, scrotal circumference, and an increase in sperm morphologic abnormalities resulting in subfertility or permanent infertility. Degenerative changes within the seminiferous epithelium occur most commonly after an insult to spermatogenesis or may be idiopathic. Common insults include trauma, stress (environmental, heat, nutritional), or toxins. Idiopathic is most often associated with age-related changes. Clinical signs of testicular degeneration are discussed along with approaches to treatment and potential prognoses as related to treatment and management practices that can be employed by the general practitioner and specialist alike. This review will also encompass a discussion on the pathophysiology of this disease so that the practitioner has a detailed understanding of the disease, which improves their ability to employ evidence-based medicine and sound clinical reasoning. Keywords: Testicular degeneration, bull, infertility, subfertility, spermatogenesis, spermiogram Introduction Testicular degeneration can be described as a diffuse disinte- gration of seminiferous tubule structure and function causing profound, subfertility of varying duration and in some cases permanent infertility. In bulls, most cases of testicular degen- eration involve both testes; unilateral degeneration does occur but is less common. Both literature reports and the authors’ clinical impressions suggest that the odds of full recovery are favorable depending on the severity of the degenerative pro- cess; however, at diagnosis, the inciting cause is most often speculative warranting at best a guarded prognosis. Softening of the testes, loss of scrotal circumference and sperm quality and quantity are consistently reported clinical signs. Watery, low sperm-concentrated ejaculates may be noticed; particu- larly in cases of bilateral testicular degeneration with high proportions of morphologically abnormal sperm, often greater than 80%.1 Testicular degeneration is an acquired condition usually lim- ited to the seminiferous tubules and rarely extending beyond the tubular basement membrane to affect the interstitial tissue. Testes undergoing degeneration may have predisposing con- genital anomalies; however, to enable differentiation from other conditions a diagnosis of testicular degeneration should be reserved for cases where the release of fully formed sperm has been previously evident indicative of postpubertal, semi- niferous tubule function. Demonstratable decreases in sperm production, sperm quality, and testicular size are fundamental diagnostic requirements for testicular degeneration. Small testis, oligospermia/azoospermia, and teratozoospermia are also observed in cases of testicular hypoplasia. Usually consid- ered to be a congenital condition, hypoplastic testis(es) do not develop normal functional capacity and never reach mature size; whereas in cases of degeneration the testis has reached mature size and full function prior to reduction in size.2 Testicular degeneration most commonly occurs secondary to an insult to the testis. Potential insults include trauma, stress, abnormal testicular thermoregulation, toxins, ischemia, nutritional deficiencies or excess, infection, sperm outflow obstructions, and neoplasia. The extent of testicular degenera- tion depends on the severity and duration of the testicular insult. Mild and short duration testicular insults may cause a transient increase in sperm morphologic abnormalities evi- dent in the spermiogram with a return to normal sperm pro- duction within days to a few weeks.3,4 In these cases, seminiferous tubule function remains intact and degenera- tion does not occur. Longer duration disturbances and severe insults that result in substantial tissue disruption may mailto:jkoziol@ttu.edu http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/ http://dx.doi.org/10.58292/CT.v15.9271 2 Citation line: Clinical Theriogenology 2023, 15, 9271, http://dx.doi.org/10.58292/CT.v15.9271 progress to degeneration.5 Testis may be able to partially or fully regenerate after degeneration depending on the extent of the damage and the quality of the repair process. Return to normal seminiferous epithelial function without fibrosis and scarring obviously favors regeneration and return to accept- able sperm quality. Cases of testicular degeneration where no inciting cause can be identified are often classified as idio- pathic. Most cases of idiopathic testicular degeneration have been observed in middle to older aged bulls; therefore, it is also referred to as age-related testicular degeneration. As the testes age, production of gametes and the production of hor- mones are adversely affected. Idiopathic testicular degenera- tion is usually progressive with a steady decline in fertility that persists indefinitely. Pathophysiology Normal testicular function is dependent on appropriate endo- crine, autocrine, and paracrine control. In the male, gonadotro- pin releasing hormone (GnRH) is secreted from the hypothalamus in a pulsatile nature resulting in waves of lutein- izing hormone (LH) and follicle stimulating hormone (FSH) release. LH acts on the Leydig cells within the testes that are responsible for synthesizing progesterone – the majority of which is converted to testosterone. This pulsatile nature of LH secretion is necessary for normal testicular function as sustained LH can lead to a refractory response from Leydig cells secondary to a downregulation in the number of receptors. This culminates in reduced secretion of testosterone from Leydig cells. High con- centrations of testosterone must be maintained for normal sper- matogenesis to occur. The pulsatile release of LH and consequently testosterone prevents negative inhibition of FSH that is needed for the maintenance of Sertoli cells. Sertoli cells convert testosterone to dihydrotestosterone and estradiol along with secreting androgen binding protein (ABP). Approximately 80% of the secreted ABP goes into the lumen of the seminiferous tubule and travels to epididymis whereas the remainder is secreted into the interstitial compartment and is absorbed into the systemic circulation. ABP binds testosterone and is responsi- ble for not only maintaining a high concentration of testoster- one within the testes but also transporting testosterone to epididymis. Although a number of causal factors are identified here it is plausible that most have similar effect, or root cause, which is a disturbance in testosterone release. Hence, a decline in testosterone secretion leads to a disturbance in spermatogen- esis that may progress to degeneration. Most common causal factors associated with abnormal sper- matogenesis are: abnormal testicular thermoregulation; hor- monal imbalances, particularly those associated with stress; and the effect(s) of toxins or expression of deleterious genes.4 Intratesticular injection with zinc acetate caused varying degrees of testicular degeneration in 10 Bos indicus bull calves. The mechanism of action of zinc acetate was unknown but was proposed to be either a direct toxic effect on testicular cells or an autoimmune effect caused by widespread disrup- tion of the blood–testis barrier. Vacuolization of Sertoli cells was also observed in this study, which often precedes a loss of germ cells.6 At least in this example, the overall significance of disturbed testosterone release likely had a minor role in the pathophysiology of testicular degeneration compared with overwhelming cellular damage leading to what appeared to be permanent degeneration. Stress typically elevates systemic cortisol concentrations, profoundly decreasing release of LH and ultimately testosterone.7–9 Stress has many origins, including environ- ment (weather, heat, humidity, nutrition, and social hierar- chy) illness, or injury; all causing changes in the spermiogram similar to those induced by disruption of testes thermoregula- tion. Cells in early meiosis including the primary spermato- cyte along with cells in spermiogenesis are extremely sensitive to alterations in the hormonal milieu secondary to stress, ill- ness, or trauma. However, earlier germ cells, including sper- matogonial stem cells, along with testicular somatic cells, which include Leydig and Sertoli cells, appear to be more resistant to adverse changes.10,11 Alterations in the hormonal milieu within testis affect semi- niferous tubules. LH, FSH, and testosterone concentrations are all affected after insults, which in turn, impairs seminifer- ous tubular function and consequently disrupting spermato- genesis. In some cases, seminiferous tubules may be severely damaged, resulting in sloughing of differentiated cells into the tubular lumen, leaving only Sertoli cells and spermatogonia. When empty tubules in the testes lose turgidity, testes become noticeably softer, and the change is recognized as testicular degeneration. Testicular degeneration may be permanent but is most often temporary or transitory. After resolution of the insult sper- matogonia may repopulate the tubules allowing testes to return to normal size and sperm production. Within a histo- logic section, there may be some normal tubules and also tubules with cellular damage accounting for varying propor- tions of normal and abnormal sperm in an ejaculate. Although there are no large-scale reports to support their belief, the authors of the current article conjecture that testicu- lar degeneration may be a more frequent occurrence in bulls in hotter and more humid climates. Disruption of testes ther- moregulation is the most understood cause of testicular degeneration.12 The most common cause of transitory testicu- lar degeneration is ‘summer infertility’ associated with season- ally elevated ambient temperatures and humidity.13 A long duration scrotal insulation study using a 20-day treatment period proved to be very effective in disrupting the testicular thermoregulatory processes sufficiently to cause degeneration in 3 of 5 treated bulls.14 Somewhat surprisingly testicular degeneration did not occur, or was at least temporary, in 2 bulls suggesting that considerable individual variation did exist. Accumulation of fat in the scrotum also limits testicular thermoregulation. Overconditioning bulls has been recog- nized as a major factor leading to testicular degeneration in cooler climates.5 Sustained elevated body temperatures associ- ated with fever can lead to testicular degeneration; however, it appears that the body’s stress response may confound the effect of heat. Localized inflammation associated with trauma may result in unilateral testicular degeneration. A number of other localized inflammatory conditions have the potential to  disrupt thermoregulatory processes sufficiently to cause testicular degeneration; however, few if any cases clearly indentifying the cause and effect have been documented. Examples include, diffuse scrotal dermatitis, severe diffuse frostbite, and orchitis. Feeding of a high starch diet to growing bulls was associated with inflammation within the testes, dis- rupted spermatogenesis and evidence of testicular degenera- tion in some bulls. A suggested cause of the testicular insult was the release of bacterial toxins after ruminal acidosis that could have caused a local inflammatory reaction within the gonadal tissue.15 Rare, congenital conditions such as congeni- tally short scrotum and incomplete testes descent into the http://dx.doi.org/10.58292/CT.v15.9271 Citation line: Clinical Theriogenology 2023, 15, 9271, http://dx.doi.org/10.58292/CT.v15.9271 3 scrotum, and acquired lesions limiting free movement of these testes may impair thermoregulatory mechanisms enough to cause degeneration.5 Higher than normal testicular tempera- tures in one testis may impede thermoregulatory mechanisms in the contralateral testis causing a disruption in spermatogen- esis or in severe cases, degeneration of both testes.13 The exam- iner may observe that while one testis feels firm, fibrotic, and clearly shrunken the other testis is larger, but soft. These clini- cal findings coupled with a watery ejaculate and teratozo- ospermia suggest that both testes are undergoing degeneration but are at different stages of the degenerative process. A detailed review of the effects of heat stress on bull fertility suggested the need for heightened awareness of the detrimen- tal effects of heat stress on bull fertility in the light of increases in global temperature due to climate change.16 Age, genetics, and husbandry practices (e.g. access to shade and water) are important considerations for mitigating the effect of heat on testicular function. Older bulls may be more susceptible to heat stress than their younger counterparts and Bos indicus bulls are more suited to maintaining fertility in hotter and more humid environments than Bos taurus bulls. Without a means of cooling, higher environmental temperatures cause heat stress within the testis. The ensuing hypoxia leads to increased reactive oxygen species production, which when in excess have a negative effect on spermatogenesis.17 Differences between breeds, individual animals, and the intensity and duration of the heat insult influence the effect on spermato- genesis and whether the disruption in testicular function pro- gresses to testicular degeneration. Scrotal insulation for 8 days was associated with Sertoli and Leydig cell dysfunction.12 Testosterone concentrations increased initially after scrotal insulation and then declined and remained low for at least 96 days; beyond when normospermia returned. This longer dura- tion scrotal insulation study was the first to demonstrate that scrotal insulation was associated with a decline in testosterone concentrations. Idiopathic, or age-related testicular degeneration in the bull largely remains an enigma with little evidence that it occurs in bulls in the scientific literature. An age-related decline in daily sperm production caused by a loss of spermatocytes during meiosis has been reported in men. This condition has been associated with a reduction in the number of Leydig cells, inter- stitial cells, myoid cells, and Sertoli cells.18 Heightened sensitiv- ity of older bulls to hotter environmental temperatures16 combined with individual variation in the response to thermo- regulatory insult14 may have a role at least in some cases. Cases of testicular degeneration with no apparent cause, most often observed in mid-aged to older stallions, are often labelled as idiopathic testicular degeneration.19 Studies of subfertile stal- lions suggested that a defect in the steroidogenic pathway, likely at the level of the testes, is probably responsible. Xenograft studies using diseased equine testicular tissue cografted with pig testis revealed that the equine tissue continued to degener- ate unlike the pig tissue following treatment with exogenous gonadotropins or endogenous hormones.19 Clinical assessment History Testicular degeneration is most often identified during a breed- ing soundness examination (BSE) as an incidental, often unex- pected, cause of subfertility. Bulls may also be presented for a perceived fertility issue. Astute individuals may notice an obvi- ous decline in scrotal circumference, severe asymmetry of the scrotum, or a failure to establish pregnancy in a cycling female(s). Bulls in use at a stud are likely to exhibit a decline in both quantity and quality of sperm in the ejaculate before other physical signs are evident. A recommended management prac- tice is that all natural service sires should have a BSE within a month or 2 of the impending breeding season. Sires used year- round, as may be the case in bull studs or in dairies employing natural service, should be examined regularly. A properly con- ducted BSE comprises a physical examination incorporating an examination of the scrotum and its contents including a mea- surement of the scrotal circumference, and an assessment of semen quality – most importantly sperm morphology. A complete history is useful in determining a possible inciting reason for testicular degeneration. For example, if the bull experienced a particularly stressful or painful situation (e.g. lameness, severe weight loss, or illness). Bulls that were over- conditioned on high-energy diets may experience substantial weight loss when placed in a new environment. All too often, bulls must transition from a high-grain diet to pasture or adapt to a low-energy diet while at the same time facing social dominance or hierarchical challenges. The quality of the feed is of little relevance if the bull cannot eat enough. A decline in scrotal circumference often occurs with a substantial decline in body weight; especially, in bulls that were overconditioned. Generally, this is thought to reflect a loss of fat in the scrotal and testicular interstitial tissue. Feeding high energy rations during the postweaning development period was associated with the deposition of fat in the scrotum causing erroneously larger scrotal circumferences, palpably softer testes, greater dif- ficulty thermoregulating the testes and poor semen quality.20 Increased fat deposition in the scrotum and testes can effec- tively insulate the testes severely compromising spermatogen- esis and causing testicular degeneration.20 High ambient temperatures and high humidity for sustained periods have also been linked to the occurrence of testicular degeneration. The clinician should always note the age and breed of the bull. Older bulls may be more susceptible to thermoregulatory challenges or age-related changes.16 Young bulls with very small testes developed testicular degeneration at 2–3 years of age.21 Small testes believed to be the result of hypoplasia and poor semen quality is a common finding in bulls of the dou- ble-muscled, Belgian Blue breed. A greater amount of intersti- tial connective tissue postulated to be interfering with internal blood flow within the testes was associated with an increased occurrence of testicular degeneration within the breed.22 Finally, a review of the bull’s previous BSE results can be valu- able. Quantifiable changes in scrotal circumference and a reliable assessment of sperm morphology are much better than owner speculation. Recent and timely BSEs can also point to a potential cause of the degeneration. Testicular degeneration may be confused with testicular hypo- plasia. Evidence of declining scrotal circumference coupled with decreasing sperm quality are important initial clues for distinguishing degeneration from hypoplasia. Physical examination Testicular degeneration in the bull may present as a unilateral or bilateral condition. Unilateral testicular degeneration is often associated with trauma; local infection; sperm outflow obstruction; or neoplasia. Causal factors for bilateral testicular degeneration are more apt to be: trauma; stress (weather, http://dx.doi.org/10.58292/CT.v15.9271 4 Citation line: Clinical Theriogenology 2023, 15, 9271, http://dx.doi.org/10.58292/CT.v15.9271 nutritional, pain, and social hierarchy); systemic illness asso- ciated with fever; insulation of the scrotum (hydrocele, ingui- nal hernia, fat, etc.); toxins; or age-related changes. A decrease in testicular volume quantified by a decrease in scrotal circumference coupled with palpable change in the tex- ture of the testes are hallmarks of the disease. A loss of palpa- ble resilience within the testis, commonly referred to as softness, is most evident early in the disease during an increase in testicular temperature.13 Testicular turgidity or resilience is created by functioning fluid-filled seminiferous tubules, com- prising 80% of the volume of a healthy sexually mature testis, surrounded by soft tissue. In long-standing cases the testes may become palpably firm; however, palpable resilience will not be evident. Testicular degeneration and testicular hypo- plasia may be difficult to distinguish; especially, in young bulls with an uncertain history as small, undersized testes are common to both conditions.23,24 Differentiation may be facil- itated by comparing the size of the affected testis to corre- sponding epididymis. Visual assessment and careful palpation of the epididymides are usually sufficient, but the examiner may also want to compare bulls of similar age. If the epididy- mis is small and proportional in size to the undersized testis, testicular hypoplasia is likely.25 Conversely, if the epididymis is well developed and near normal size, one can assume that testicular and epididymal development were normal and that testicular degeneration and corresponding testicular atrophy has occurred. It is also important to remember that testicular hypoplasia is a congenital condition.2 Severe cases of degeneration can progress to testicular fibrosis. Damage to the seminiferous tubule lining may not be repair- able resulting in scarification and calcification of the tissue. Fibrosis appears on ultrasonography as echogenic densities. Reports from western Canada and Argentina indicate that fibrotic lesions in testicular tissue are quite common and not necessarily associated with a tangible decline in fertility.26 The underlying etiology of testicular changes resulting in testicular fibrosis remains speculative and congenital malformation of the tubule-to-rete connection, infectious disease processes resulting in tubule destruction, and trauma to the testes have all been proposed. Testicular fibrosis may range from a few small areas with no effect on fertility to severe fibrosis through- out the testes. The presence of many fibrotic lesions may not preclude production of an ejaculate with normal morphology, as some bulls with severe fibrosis produced semen with up to 94% morphologically normal sperm in a report. The authors suggested that large amounts of scar tissue would be expected to reduce sperm production, but that changes in semen pro- duction by bulls with varying degrees of severity of testicular fibrosis has not been investigated.26,27 Ultrasonographic evaluation of the testis will not allow for differentiation between normal testicular tissue and that which has lost germinal epithelium.28 Ultrasonography after induced testicular degeneration by scrotal insultation failed to demonstrate a correlation between pixel intensity and semen quality during BSE.29,30 Furthermore, pixel intensity for predic- tion of future fertility had limited correlation with BSE out- comes.31–33 Echogenic areas varying in number and size are frequently detected in the testis and associated with fibrosis, but they do not have substantial effect on the percentage of normal sperm within the ejaculate.26 Summarizing these reports, ultrasonography can be useful for determining that fibrosis is indeed present but is not useful for predicting the quality of sperm produced or the outcome of a BSE. Semen assessment Testicular degeneration follows an insult to spermatogenesis. Decreased sperm production and the appearance of teratozo- ospermia in the ejaculate occur soon after the insult and if monitored regularly over a few weeks, a predictable series of defects will appear sequentially. The seminiferous epithelium is lined with 5-7 layers of germinal cells supported and nour- ished by Sertoli cells. From A1 spermatogonia at the basement layer of the tubule epithelium to fully formed sperm ready to be released into the tubule lumen requires ~ 61 days in the bull. An additional 10 days is needed for transport to and through the epididymis during which further maturation of sperm occurs. Cells in meiosis and spermatids undergoing the final metamorphic changes to become fully formed sperm, known as spermiogenesis, are the most sensitive to adversity. Cells lost in meiosis simply degenerate, the process of sper- matogenesis ends, and no subsequent generations of cells are produced leading to reduced sperm output. Disruption of crit- ical maturation processes for spermatids, and recently released sperm in the testes and epididymis leads to the appearance of morphologic abnormalities in the spermiogram.3,11 Mild dis- turbances may only affect spermatids or epididymal sperm with a short-lived period of increased numbers of morpholog- ical abnormalities. A study characterizing the sequential appearance of morphologic abnormalities reported that there were differences between animals in the overall degree of response to the negative stimulus reflected in the proportion of morphologically abnormal sperm and the proportion of certain types of defects.4 More severe or prolonged distur- bances cause destruction of the spermatocytes and sper- matogonia. Not all tubules will be affected in the same way; however, it is widespread degeneration in the tubules that causes the noteworthy changes that define the condition. Spermatocytes that are disrupted during meiosis and survive the remainder of the spermatogenic process may have chro- matin abnormalities leading to reduced fertility and poor embryo survival.16 Because testicular degeneration is the out- come of a progressive process, changes in semen characteris- tics become evident before identifiable changes in scrotal circumference or palpable texture of testis. Oftentimes, an assessment of semen quality does not occur until sometime after the insult when widespread seminiferous tubule disruption has already progressed to degeneration. Physical examination of testes may initiate suspicions of testicular degeneration in these cases and subsequent examination of sperm morphology will help confirm the diagnosis. The appearance of teratozoospermia is commonly observed in cases of testicular degeneration. No single morphological aberration is exclusive to degeneration. Small numbers of spheroids, which are believed to be immature spermatogenic cells may be seen as well as teratoid forms and medusa cells. Distal midpiece reflexes, proximal cytoplasmic droplets, Dag- like and other midpiece disruptions, coiled principal pieces, detached heads, tapered and pyriform heads, knobbed acro- somes, all types of nuclear vacuoles, microcephalic sperm and sperm with abnormal DNA condensation were evident fol- lowing known insults to spermatogenesis.3,4 The sperm head or nucleus is largely made up of chromatin. Variations in nuclear shape within a spermiogram may reflect varying levels of chromatin stability. Using conventional microscopic tech- niques even normal appearing sperm may have poor chroma- tin and reduced fertility.34 Bulls recovering from a severe disturbance to spermatogenesis and testicular degeneration often will produce sperm with more variation in nuclear size and shape. In the unstained semen sample immature sper- matogenic cells may be confused with white blood cells. Different stages of immature spermatogenic cells typically http://dx.doi.org/10.58292/CT.v15.9271 Citation line: Clinical Theriogenology 2023, 15, 9271, http://dx.doi.org/10.58292/CT.v15.9271 5 appear in an ejaculate that allow for a variation in size of the cells as compared with white blood cells, which are more uni- form in size. To differentiate between an immature spermato- genic cell and a white blood cell a semen smear can be air dried and stained in Diff-Quik® (available from numerous suppliers) or very similar Wright-Giemsa stain. Neutrophils and lymphocytes will be stained by Diff-Quik® whereas imma- tures spermatogenic cells will not be stained sufficiently to allow the practitioner to easily differentiate.24,35 The duration of the insult and the time that passed from the initial insult, assuming that it was acute in action, will dictate the sperm morphologic abnormalities that will be observed, and the sequence of the abnormalities noticed. Oligospermia and asthenozoospermia may also be noticed in ejaculates. The majority of beef bulls in North America are natural service sires and are not trained to an artificial vagina for semen collection. Semen samples collected by other means (e.g. electroejacualtion or transrectal massage) are not repre- sentative of a physiologic ejaculation. While sperm concentra- tion can be calculated samples may be more or less concentrated than a natural ejaculation and therefore, not truly representative of what the bull can produce. It is also important to remember that sperm motility can be altered by environmental conditions. Samples obtained by massage are especially prone to chilling. Nevertheless, effectively per- formed electroejaculation and transrectal massage are both very suitable methods for clinical assessments of quantity and quality of sperm production.36 Endocrinologic evaluation The relationship between plasma hormone concentrations and testicular degeneration in bulls has not been adequately studied. In other species (e.g. the stallion) estimation of circu- lating hormone concentrations is an unsatisfactory diagnostic tool for testicular degeneration.24 Due to daily and seasonal fluctuations in hormone, detecting changes between normal and pathological concentrations is difficult for diagnosing tes- ticular degeneration preemptively or during the early stages of disease. By the time that hormone concentrations become consistently inappropriate, the diagnosis is readily apparent by physical examination.24 Histopathologic evaluation Histopathologic evaluation of a testis affected with testicular degeneration will reveal cytoplasmic vacuolization, absence of later stage germ cells and loss of architecture of the seminifer- ous epithelium.21 Although histopathologic findings can help to define testicular degeneration and testicular biopsy would provide definitive evidence, it is rarely justified. Once the prac- titioner has obtained a satisfactory history and performed a proper BSE a diagnosis of testicular degeneration can be made with confidence. It should also be considered that a single biopsy may not be representative of the testes as a whole.24 Testicular biopsies can be safely performed with no subse- quent decrease in sperm quality appreciated after biopsy.37 This study was performed on normal bulls and no information exists regarding the use of this procedure on the already degen- erated or compromised testicle.37 Although a testicular biopsy may be useful in some cases often the quality of the sperm ejaculated will give a similar insight into the health of the sem- iniferous epithelium without the potential risks associated with a testicular biopsy. Effects of feeding a high energy feed were studied. A starch rich diet was fed to Angus x Charolais bulls (n = 40) for 94 days with a mean age of 14 ± 1.7 months at the beginning of the trial.15 After a 10-day period of adapta- tion, body weight, an assessment of testes size, and ultrasonog- raphy of the testes were performed every 28 days from the beginning of the measurement period until day 84. At the end of the experiment each bull underwent electroejaculation and semen analysis. The testes were harvested at slaughter and sub- mitted for an assessment of histological architecture with evi- dence of degeneration and tissue healing, seminiferous tubule atrophy, and evidence of disruption of spermatogenesis being scored. Mean scrotal circumference and testes volume increased as expected throughout the feeding period yet lesions consis- tent with degeneration were observed including sperm with vacuoles, tubules with thickened basement membranes, inter- stitial tissue edema, multinucleated giant cells in the lumen of tubules and tubular atrophy. There was also evidence of per- manent tissue damage including fibrosis, microcalcification, and complete loss of seminiferous tubules; although, the fre- quency of these lesions was low amongst analyzed samples. However, evidence of an insult to spermatogenesis was present on 100% of the histograms.15 Although examination of testes histopathology is not practical in most settings the occurrence of degenerative changes, including permanent lesions, varied between individuals and areas within the testic.15 Treatments, management, and prognosis Recovery from testicular degeneration is possible in most cases if the initiating cause is removed. Three, 4 or even sev- eral months may be required for the seminiferous epithe- lium to recover to preinsult sperm production. No treatment has been successful in treating testicular degeneration other than removal of the initial trauma or stressor. Partly due to the usual uncertainty in determining the cause of the degen- eration compounded by the individual variation that is evi- dent following any insult to spermatogenesis predicting when a satisfactory BSE should be expected is a risky, if not impossible, undertaking. When breeding season is imminent it is usually best to cull and replace all but the most valuable bulls. Valuable bulls may be worth feeding and housing for several months provided a worthwhile return to normal sperm production is plausible. The use of GnRH treatment in a Belgium Blue bull with testic- ular degeneration has been described. In that report an osmotic pump was inserted subcutaneously, and the bull received frequent doses (2.5 µl/h) of buserelin for 9 weeks. After treatment an increase in sperm concentration, volume and quality was noticed. The treatment did allow the authors to determine that the bull suffered from hypothalamic dys- function. One could surmise that once treatment stopped the bull would return to a state of testicular degeneration.38 No other studies reported on the use of buserelin. In stallions GnRH has not been shown to be effective as a treatment for testicular degeneration in controlled studies.24,39 In cases of unilateral testicular degeneration or damage, removal of the compromised testis has been advocated in hopes of salvaging valuable genetics. Especially in those instances where infammation persists; for example, an abscess, sperm granuloma or tumor; heat radiating from the damaged testicle may overwhelm the physiological mecha- nisms maintaining the contralateral testis 4–5°C below body temperature leading to secondary testicular degeneration.40 Aside from weighing the likelihood for recovery, the deciding http://dx.doi.org/10.58292/CT.v15.9271 6 Citation line: Clinical Theriogenology 2023, 15, 9271, http://dx.doi.org/10.58292/CT.v15.9271 factor to perform a hemicastration should be that the inflam- mation associated with postoperative tissue healing will be short-lived compared with leaving the compromised testis in situ. Another reason to consider hemicastration, is that the blood–testis barrier within the compromised testis may have sustained damage leading to the production of fertility limit- ing antisperm antibodies.24,41 Removal of 1 testis often results in hypertrophy of the remaining testicle. The remaining testi- cle will produce 1.5 X the sperm production of 1 testis leaving a bull at ~ 75% of his original sperm production ability.42 It should be noted that the hypertrophy only occurs in normal testes and a contralateral testis damaged by excessive heat for prolonged periods or has exposure to antisperm antibodies cannot be expected to achieve such results. Conclusion Testicular degeneration in the bull is often discovered on a bull BSE; therefore, determining a cause may be difficult. An insult to the testis(es) resulting in a disturbance of spermatogenesis that progresses to a disruption of the seminiferous epithelium is the most common sequence of events although poorly understood idiopathic or age-related testicular degeneration can be observed in some bulls. Disruption of testes thermoreg- ulatory mechanisms is the most studied model for inducing testicular degeneration and may be the most common cause of spontaneously occurring testicular degeneration with overfeed- ing, obesity, age, and ambient heat/humidity being substantial risk factors. Although not definite, it appears that both thermo- regulatory and stress-induced testicular degeneration involve a disturbance in the hypothalamic–pituitary–gonadal axis result- ing in insufficient testosterone concentrations to maintain sem- iniferous tubule function; however, an endocrine disturbance may not be evident when the animal is presented for a clinical examination. Evaluation of the quality and quantity of sperm combined with examination of testes often supports a defini- tive diagnosis. Histopathology and ultrasonography may be of benefit in some cases but are often not warranted. 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