Introduction

Degeneration of the testis parenchyma may be temporary or permanent. Temporary degeneration is by far the most common form of degeneration and, with removal of the cause, the potential for recovery of testis function is good. It may be difficult to distinguish between a severe disturbance of spermatogenesis, with a marked decline in semen quality, and degeneration. The use of the term “degeneration” is arbitrary, but usually means there has been a loss of scrotal circumference, the testes may feel soft, and the percentage of normal sperm has declined to extremely low values, usually less than 20%. With temporary degeneration there is loss of germinal cell layers near the lumen in many or all of the seminiferous tubules. Sertoli cells and spermatogonia, which are more resistant to damage, are likely to be retained in the tubules, and after the cause of degeneration is removed these cells serve to repopulate the tubules with spermatocytes and spermatids with an accompanying increase in testis size and semen quality. Advanced degenerative changes resulting in permanent damage include spermiostasis, tubular mineralization, granuloma formation, thickened basement membranes, and fibrosis in focal or diffuse areas of the parenchyma.

Pathogenesis

Factors involved in the pathogenesis of testis degeneration include abnormal thermoregulation of the testes, nutritional excesses or deficiency, toxicity, inheritance, congenital blockage of sperm outflow from the testes, infectious disease, severe trauma, and senile atrophy.

The testes of scrotal mammals function normally when testis temperature is maintained at 2–6 °C less than body temperature.¹ Scrotal insulation has been used in many experiments to produce temporary testicular degeneration.^2,3 An experiment involving scrotal insulation for up to 10 days was conducted to determine whether abnormal thermoregulation might induce fibrotic testes lesions.⁴ Scrotal insulation resulted in severe changes in semen quality, but did not result in any fibrotic lesions within 6 months after insulation. Therefore, abnormal thermoregulation of the testes that is reversible (e.g., obesity) may not be a common cause of permanent damage. Other less common causes of chronic abnormal thermoregulation that may lead to temporary or permanent testicular degeneration include severe chronic scrotal dermatitis, heat and swelling due to orchitis, trauma, chronic illness which may involve prolonged fever and endotoxins that are potent inhibitors of gonadotropin secretion, a congenitally short scrotum, severe scrotal frostbite leading to loss of testis mobility within the scrotum, and incomplete descent of a testis into the scrotum due to hereditary or congenital factors.

Obesity is a leading cause of testis degeneration in bulls. The prevailing feeding and husbandry practices throughout North and South America and in many countries of the world fatten bulls for shows and sales. Many bulls become obese and fat accumulates in the scrotum leading to chronic abnormal thermoregulation with increased testicular temperatures.² After loss of fat from the scrotum, regeneration of seminiferous tubules may occur with return to normal sperm production.⁵

Nutritional deficiencies are seldom to blame for testis degeneration in bulls. Naturally occurring deficiencies are usually multiple and deficiency of any single nutrient as a cause of bull infertility has rarely been reported. Vitamin deficiencies are likewise rarely observed as a cause of infertility in the larger male domestic animals if forages are normal in quality or quantity. Poor feed quality resulting in loss of body weight may depress spermatogenesis via an endocrine effect rather than by a direct effect of specific vitamin or mineral deficiencies on developing germ cells. One study showed that protein supplementation of bulls on poor-quality forage significantly increased dry matter intake, enabling maintenance of live weight. In unsupplemented bulls, weight loss was accompanied by a significant decrease in scrotal circumference and daily sperm production per gram of testis. However, histological sections did not indicate any apparent differences in seminiferous tubule activity between bulls that received protein supplementation and bulls that did not.⁶ Vitamin A deficiency can cause testicular degeneration in laboratory rats,⁷ but in bulls under practical feeding conditions, diets that result in long-term marginal vitamin A deficiency or a relatively short-term absence of vitamin A intake probably have minimal effects on spermatogenesis.⁸ There is little evidence that deficiencies of vitamins B, C, D, or E are even occasional causes of infertility in domestic animals.⁹ Although vitamin E is essential for reproduction in the rat, naturally occurring deficiencies resulting in testis degeneration in livestock have not been reported. Mineral deficiencies may affect reproduction in male animals, but reports are rare. Deficiencies of calcium, manganese, zinc, iodine, potassium, and selenium have not been proven to be causes of testis degeneration. Deficiencies of phosphorus, cobalt, iron, zinc, and copper may cause anemia, lack of appetite, and loss of weight and thus adversely influence reproduction. Deficiencies of these minerals are often associated with a lack of protein and low levels of vitamin A.

The potential of many drugs, chemicals, and heavy metals to cause testis degeneration has been shown by intentional experimental exposure (mainly of rats and mice); however, there are very few reports of naturally occurring cases in bulls.^9,10 Ingestion of plant toxins may cause testis degeneration. Fusarium mold in grain crops is common and one of the toxins produced is zearalenone. Zearalenone, which has an estrogenic effect, has the potential for detrimental effects on semen quality and testis degeneration. In one report, 23 young rams became infertile on a farm where the animals were fed grain containing zearalenone 5–20 mg/kg for several months. Two bulls fed maize containing zearalenone 20 mg/kg for 72 days had poor semen quality after 21 days. Histological examination of the rams’ testicles showed complete destruction of the germinal epithelium and aspermia. In the bulls, degeneration of the germinal epithelium was marked only in certain areas of the testicles, but more than 75% of sperm were in a degenerated form.¹¹ Cottonseed meal in the diet may expose bulls to the effects of gossypol toxicity. Gossypol causes alterations in mitochondrial structure and function. This results in abnormalities of spermatocytes, spermatids, and mature sperm.¹² Although gossypol affected semen quality, testicular degeneration did not appear to be associated with gossypol.^13,14 Locoweed (Astragalus lentiginosus) has the potential to cause temporary testis degeneration as was shown by experimentally feeding locoweed to mature rams.¹⁵ The use of growth-promoting implants has the potential to impair testicular development.^16,17 When bulls were implanted with zeranol (Ralgro) at birth and at 3 and 6 months of age, or every 3 months from birth through 18 months of age, scrotal circumference was reduced but tended to recover with increasing age. There was little effect on the reproductive organs when bulls were implanted with zeranol after 7 months of age.

Congenital and inherited disorders of the testes and epididymis may be involved in testis degeneration. Young bulls with testicular hypoplasia may produce semen with satisfactory quality, but are more prone to develop testicular degeneration at 2–3 years of age.¹⁰ In young bulls a small scrotal circumference has been correlated with a lack of germinal epithelium within the seminiferous tubules.^18,19 Hypoplasia may be unilateral or bilateral. Some authors report that most cases are unilateral and that the left side is more frequently affected,¹⁰ but there appears to be no precise definition for testicular hypoplasia based on physical measurement. Histologically, testicular hypoplasia is defined based on cell populations in the seminiferous tubules. Testicular hypoplasia is congenital and possibly hereditary in origin. It has been studied in Swedish Highland cattle in which it appears to be caused by an autosomal recessive gene with incomplete penetrance.²⁰ The condition exists in many breeds today, although at a very low frequency.²¹ Double muscling (myofiber hyperplasia), which is inherited as an autosomal recessive trait, is associated with a high incidence of bilateral testicular hypoplasia;²² however, it appears there is no information available to compare the incidence of testis degeneration in double-muscled breeds and non-double-muscled breeds.

The embryo needs to connect its gonads with the mesonephric urinary system in order to develop its reproductive excurrent duct system. The connection comes via the rete tubules that develop between the fetal gonad and the mesonephros. The ureter for the mesonephros, the mesonephric duct, will become the epididymis. The efferent ductules develop from the mesonephric tubules and join to the mesonephric duct via the rete tubules during embryonic development. Failure of some of the efferent ductules to join with the rete may later (at puberty) result in sperm impaction of the blind-ending ductules. Rupture of sperm-impacted ductuli would lead to formation of sperm granulomas. If all the efferent ductules are obstructed, the seminiferous tubule fluid and sperm that are produced cannot leave the testes. The testes may become enlarged and edematous and then degenerate.

Infectious organisms may be involved in testis degeneration. Eperythrozoon infection in a group of young bulls led to anemia, scrotal and hindlimb edema, and soft testes. Loss of scrotal thermoregulation was likely the main cause of testicular degeneration and poor semen quality.²³ In another report, testicular degeneration and loss of libido occurred when beef bulls were experimentally inoculated with Anaplasma marginale.²⁴ Testicular degeneration was confirmed by histopathology and semen evaluation. Picornavirus and bovine enterovirus isolated from semen and feces of a bull were implicated as a cause of orchitis, testicular degeneration, aspermatogenesis, and loss of libido in a bull.²⁵