Abnormal testicular descent (cryptorchidism, ectopic testis) in dogs and cats

The descent of the testes from the abdominal cavity where they originate is the characteristic feature of animal species defined as having externalised testes. In such animals the prepubertal location of the testes outside the abdomen ensures an intratesticular temperature 3-5°C lower than body temperature, a condition necessary for spermatogenesis. Abnormal testicular descent refers to the lack of descent of one or more of the testes into the scrotal sac within a defined time for each species. It is a defect of male gonadal development during foetal/neonatal life, but is manifested clinically only after birth. Two main forms can be distinguished on the basis of the final location of the gonad:  “cryptorchidism”, in which the stage of intra-abdominal or intra-inguinal migration is altered and the gonad remains within the abdominal cavity, and “ectopic testis”, in which the testis is located outside the abdomen or inguinal canal. Both these forms of abnormal testicular descent should be differentiated from monorchidism and anorchidism, terms which indicate agenesis (lack of formation) of, respectively, one or both of the testes.

Abnormal testicular descent is a condition that can occur in all mammalian species with externalised testes; the first descriptions in humans, dogs and rams go back as far as the 17^_th century. Until a few decades ago, it was general scientific opinion that abnormal testicular descent was an isolated disorder, characterized by a moderate heritability mainly related to male genes. New genetic findings have, however, led to the hypothesis of a polygenic, recessive model of inheritance such that abnormal testicular descent is currently considered a multifactorial genetic condition whose development has epigenetic and environmental determinants as well as genetic ones.

Many researchers consider abnormal testicular descent an “alarm sign” of the more complex “testicular dysgenesis syndrome”, characterized by a series of abnormalities of the male gonads such as qualitative and quantitative defects of spermatogenesis and anomalies of testicular cell differentiation, often resulting in malignant transformation. It should, however, be remembered that abnormal testicular descent is not always accompanied by these defects and, vice versa, the presence of normal testicles does not guarantee immunity against the development of other gonadal disorders.

Besides its consequences on fertility and the possible development of other, sometimes severe, disorders, abnormal testicular descent is a redhibitory fault in the case of a sale; thus, the buyer can call the contract void and return the animal, demand a reduction in the price of the sale or claim compensation for any veterinary procedures related to the redhibitory fault.

SIGNALMENT AND CLINICAL HISTORY

The frequency of abnormal testicular descent in dogs ranges from 1.2% to 15%; this large variability in frequency is due to the fact that certain breeds are predisposed to development of the condition (Table 1). In general, small dogs (<9 kg) have a higher risk than medium-sized (9-18 kg) and large (>18 kg) animals. In 20% of affected subjects, the condition is bilateral, while in most cases (80%) only one gonad is affected, with the right testis being involved more frequently than the left one (66% versus 34%, respectively).

As far as concerns cats, the reported frequencies of undescended testes range between 0.3% and 1.9%. The condition is usually unilateral (80-90% of cases) and 72% of such cases are ectopic testis; in contrast, bilateral abnormal testicular descent is always cryptorchidism. Unlike in the dog, there is no clear evidence of a different frequency of involvement of the right and left testes, although some authors have reported a more frequent involvement of the left testis (60%) than the right one (40%).

The age of the animal is of fundamental importance when making a diagnosis of undescended testes (see later), but not to a predisposition to its occurrence in that, as explained above, this is a genetically determined syndrome. Given that the genes responsible for its occurrence are autosomal genes, i.e. not sex genes, they can be present in both males and females; the clinical manifestations can, however, occur only in male homozygotes, given that only these animals have male gonads.

Dogs with abnormal testicular descent have a greater predisposition to the development of other congenital defects including recurrent patellar luxation (7%), palpebral anomalies (3%), inguinal hernias (1.3%), umbilical hernias (0.6%), hip dysplasia and defects of the penis and/or prepuce. In the cat there are no data demonstrating the hereditary nature of abnormal testicular descent; nevertheless, cryptorchid subjects of this species, too, often have other congenital defects such as patellar luxation, tail defects, cardiac malformations, tarsal deformities, micro-ophthalmia and palpebral abnormalities.

Table 1. Dog breeds predisposed to abnormal testicular descent in decreasing order of risk.

AETIOPATHOGENESIS

The aetiopathogenesis of abnormal testicular descent has not yet been completely clarified. Indeed, besides inherited genetic causes, a series of physical and other phenomena have been suggested to be able to affect the normal process of descent of the testes into the scrotum.

Normal testicular descent occurs in three stages: (i) intra-abdominal migration, in which the gonad is propelled caudally to the developing kidney, reaching the internal inguinal ring; (ii) intra-inguinal migration, through the abdominal wall; and (iii) inguino-scrotal (or extra-inguinal) migration, as the gonad assumes its definitive position in the scrotum. Failure or lack of completion of any of these three stages causes the arrest of the testicle along its migration pathway at three possible levels (intra-abdominal, inguinal and prescrotal), while altered inguino-scrotal migration can lead to an ectopic testis (parapenile, perineal, crural) (Figs. 1 and 2).

Numerous factors act together to produce correct testicular descent. According to their nature, these factors can be divided into mechanical/physical or hormonal. One of the fundamental physical factors is the presence of the gubernaculum testis, a transitory embryonic structure responsible for dragging the testis into the scrotal sac as the gubernaculum goes through a growth spurt followed by a period of regression; the development of the gubernaculum is also essential for the expansion of the inguinal ring during the second (inguinal) stage of testicular migration. Other mechanical/physical factors are the weight of the gonad itself and the pressure applied by the correct development of the abdominal organs and the abdominal wall. For this reason, both abnormal development of the gubernaculum testis, and changes in the gonadal load or intra-abdominal pressure can prevent correct testicular migration; possible causes of undescended testes, therefore, also include incomplete testicular development, umbilical infections complicated by peritonitis and trauma of the inguinal region.

There is a also a complex chemical/hormonal control system exercised by nerve centres and the testis itself through the secretion of hormones and other substances. Besides the well-recognized effects of hormones such as gonadotropin-releasing hormone (GnRH), luteinising hormone, oestrogens, androgens and anti-Mullerian hormone, recent studies have demonstrated the fundamental roles of other molecules.

The first stage of testicular migration (intra-abdominal) is dominated by the action of insulin-like peptide 3 (Insl3), which, secreted by the Leydig cells of the testis, promotes the growth of the gubernaculum testis, which is essential for “anchoring” the gonad and dragging it towards the inguinal canal.  Calcitonin gene-related peptide (CGRP), released by the genito-femoral nerve in response to stimulation by androgens, has a sort of attracting effect on the gubernaculum testis, stimulating its growth and orienting its movement in an inguino-scrotal direction. This peptide is, therefore, essential for the correct progress of the last stage of testicular migration. Insufficient secretion of these substances and impaired function of their respective receptors are among the causes of abnormal testicular descent. The primary cause of abnormal testicular descent is, therefore, the testis itself, or more precisely, failure of its correct physical development or adequate endocrine secretory activity.

SIGNS

The main sign in subjects with abnormal testicular descent is the absence of one or both of the testes from the scrotum. Undescended testes are often small, especially if they have been retained in the abdominal cavity (Figs. 3 and 4). Microscopic damage in undescended testes includes a reduction in the diameter of the seminiferous tubules and atrophy/hypotrophy of the germinal cell line, which occurs earlier and to a greater extent in cases of cryptorchidism than in ectopic testes.

Spermatogenesis in undescended testes is altered because of the higher temperature to which the gonads are exposed; this is manifested by an oligospermic or teratozoospermic ejaculate. Despite the presence of changes in the ejaculate, individuals with unilateral abnormal testicular descent and, according to some authors, with bilateral ectopic testes should be considered potentially fertile. In contrast, subjects with bilateral cryptorchidism are sterile; they can, however, have a reproductive instinct and show sexual excitation, since the gonadal endocrine activity is preserved.

Other signs that can occur in subjects with abnormal testicular descent are those related to the abovementioned congenital defects associated with the gonadal disorder. More serious signs can derive from the neoplastic transformation of the undescended testes and related paraneoplastic syndromes; the risk of testicular malignancies is from 9 to 13.6 times higher than normal in subjects with abnormal testicular descent and these animals have a predisposition to the development of Sertoli cell tumours, associated, in 30-50% of cases, with the so-called “feminisation syndrome”. This syndrome is due to the particular behaviour of some malignancies of the Sertoli cells, which alter the hormonal production of the neoplastic testis, leading to the predominant production of oestrogens and inhibin. This alteration in hormonal production is associated with systemic effects and causes real feminisation of the animal, manifested as symmetrical, bilateral, non-pruriginous alopecia of the trunk, palmar region of the hind limbs and inner thighs, gynaecomastia with possible galactorrhoea or new breast formation, attraction of males, thinning of the skin, hypotrophy/atrophy of the thyroid gland with consequent lethargy, squamous metaplasia of the prostate, pendulous prepuce and bone marrow suppression. Furthermore, the spermatic cord of the undescended testis, particularly in the case of cryptorchidism, can easily undergo torsion, leading to a characteristic syndrome of acute abdomen. In unilateral abnormal testicular descent the feminising effect of the undescended testis causes atrophy of the contralateral scrotal testis.

In humans it has been demonstrated that abnormal testicular descent should be considered a condition of the subject and not of the single testis, emphasizing the abnormalities of the contralateral scrotal testis (considered dysgenetic and, therefore, equally likely to undergo malignant transformation) in the unilateral forms. This dysgenetic condition of the contralateral scrotal testis has not yet been demonstrated in domestic animals; in a study of dogs under 2 years of age, histological abnormalities were not found in the contralateral scrotal testis of animals with unilateral testicular malposition prior to the development of any malignant transformation.

DIAGNOSIS

One of the essential criteria to respect when diagnosing testicular malposition is the time limit. Although the testes should be within the scrotum already at birth in the cat and within 10 days of birth in the dog, gonads may move within the inguinal canal until the closure of the internal inguinal ring, which occurs at about the age of 6 months in dogs and 7/8 months in cats. A definitive diagnosis of abnormal testicular descent cannot, therefore, be made before this event.

The diagnosis is suspected whenever an animal lacks one or both of the gonads in the scrotum. The signalment is important not only with respect to the age of the animal, but also with regards to the breed, which may be one with greater predisposition to this problem. Pedigree information can also be diagnostically relevant, given the genetic nature of the disorder.

During the clinical examination, care must be taken to look for all possible signs related to the genetic anomalies that are often found in subjects with abnormal testicular descent; analysis of the secondary sexual characteristics (development and distribution of the muscle mass, skin thickness, characteristics of the coat) may indicate the presence of hormone-secreting tissue and, therefore, support or refute a suspicion of abnormal testicular descent rather than anorchidism.

The general conditions of an affected subject are usually good. The exception is when the undescended testis has undergone malignant transformation with its related consequences. In these cases, the testicular malposition is obviously not the main clinical problem and the diagnosis and treatment must be aimed at identifying and controlling the damage related to the malignancy.

Palpation of the scrotal and inguinal regions must be carried out gently and meticulously; it must not be forgotten that the testicles of whelps of a few months old are small, soft and very mobile and can, therefore, easily be confused with adipose tissue or lymph nodes or even not detected. Furthermore, stimuli such as fear and cold cause contraction of the cremaster muscles which draw the gonads back up into the inguinal canal, making them difficult to detect by palpation.

In dogs, the differential diagnosis between bilateral crytpochidism and anorchidism can be helped by palpation of the prostate; a larger volume of this gland, which characterizes sexually integral animals, may suggest the presence of androgen-secreting tissue. In cats, inspection of the penis may reveal the presence of particular growths called “horny spicules”, an unequivocal sign of current or recent (within the preceding 6 weeks) androgen production (Fig.  5).

Hormonal stimulation is considered the best diagnostic investigation in bilateral cryptorchidism: the aim is to determine whether there is a increase of the basal concentrations of testosterone following stimulation with GnRH or human chorionic gonadotropin. Since testosterone is secreted in a pulsatile manner, when conducting the so-called “challenge test” blood samples should be taken repeatedly after the administration of GnRH (2 μg/Kg i.m.). Increased levels of testosterone after the stimulation constitute definite proof of the presence of a retained testis. Ultrasound examination is rarely useful given the small size of the testicles. The diagnosis is confirmed by finding the malpositioned gonad during surgical exploration (Fig. 6).

TREATMENT

The treatment of choice for both unilateral and bilateral altered testicular descent is bilateral orchidectomy. This operation fulfils the need to prevent reproduction in animals with unilateral abnormal testicular descent, which are potentially fertile but may transmit the defect, but above all the need to prevent or treat the possible malignant transformation of undescended testes.

Furthermore, if the theory of dysgenesis of the contralateral scrotal testis were to be demonstrated to be true also in domestic animals, bilateral orchidectomy would prevent possible neoplastic transformation of the apparently normal scrotal testis. However, as discussed above, there is currently no evidence that the scrotal testis in dogs with unilateral testicular malposition is dysgenetic and, therefore, its seems reasonable to remove only the undescended testis in dogs under 2 years old with no evident pathology of either the undescended testis or the scrotal one, and monitor the remaining scrotal testis carefully to pick up any abnormalities promptly.

As stated above, animals with bilateral cryptorchidism are sterile; in this case the management is not, therefore, aimed at preventing possible genetic transmission of the condition, but rather to remove gonads predisposed to neoplastic changes and to the risk of torsion of the spermatic cord. It is, therefore, a choice to make to guarantee the animal’s future wellbeing. In the case of unilateral abnormal testicular descent, the need to prevent genetic transmission of the disorder is additional to the already mentioned risk of malignant transformation of the undescended testis and, possibly, of the contralateral one. 

The surgical technique used depends on the suspected site of the malpositioned testis (Fig. 7). In cases of bilateral cryptorchidism, the testes are often located caudally to the kidneys, while in cases of unilateral cryptorchidism the testis is often found in the caudal part of the abdomen (Fig. 8), lateral to the bladder. The best method for locating a retained testis is to retroflex the bladder and identify the vas deferens (Fig. 9). Possible complications during castration of cryptorchid subjects include damage to the ureters, prostatic urethra or prostate. Ectopic testes may be found in parapenile, prescrotal, perineal and crural sites.

The alternative to orchidectomy is orchidopexy, in other words, surgical relocation and fixing of the testes within the scrotal sac. This is a very controversial procedure, since animals with this pathology should not be allowed to reproduce and cannot be exhibited at shows and competitions. Furthermore, it must be remembered that undescended testes are still predisposed to neoplastic changes even after they have been fixed in the scrotum.

There are case reports of successful non-surgical repositioning of testes achieved simply by gentle traction of the gonads towards the scrotum; however, there are no scientific data on this management.

Medical treatment with GnRH has been tried in both cats and dogs with different results; while this management is unsuccessful in cats, a success rate of 20% in dogs under 6 months old has been reported. These studies did not, however, include a control group and it is not, therefore, possible to be certain that the testicular descent was due to the effect of the treatment rather than to normal gonadal development. Furthermore, considering all the observations discussed above, medical treatment cannot be recommended.

PROGNOSIS

Survival is not affected by abnormal testicular descent unless malignancy or testicular torsion occurs. The functional prognosis, however, is always poor in bilateral cryptorchidism, since the affected animal is sterile. Given the genetic and, therefore, hereditary nature of the condition, reproduction is advised against even in cases of unilateral abnormal testicular descent in which the undescended testis has not developed malignant changes.

PREVENTION

It is very difficult to identify female carriers of this disorder; only after a female has given birth to at least 40 male whelps not affected by altered testicular descent can she be definitely considered not to be a carrier. The main form of prevention is, therefore, to not allow affected males to reproduce.

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