Cryptorchidism in a dog

Keywords: canine, cryptorchid, testicle

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The reproductive tract of a seven month old Border Collie (hit-by-car). This dog had a well-developed prostate gland and os penis and the penile frenulum had almost disappeared. The frenulum is visible here as the thin, clear membrane on the ventral part of the extended penis. All these are signs of adequate androgen production. The left testicle was retained in the abdomen. Note how much smaller the left testicle is than its counterpart; mainly due to the absence of spermatogenesis. See histology below.

One should remember however, that the effect of cryptorchidism on steroidogenesis is for all practical purposes, negligible.

The right testicle was present in the scrotum but was separated from the rest of the ductus deferens when the tract was retrieved. The missing section of the ductus deferens is indicated here by the dotted line. To illustrate the fact that the ductus deferens runs medially and caudally in normal descended testicles (and indeed in this case too), it has been rotated clockwise (green arrow) to show that anatomy. The parietal vaginal clinic (PVT) has been stripped away from the descended testicle in order to show these structures. In the retained testicle of course, there is no vaginal tunic around the testicle therefore the testicle and epididymis are immediately visible.

The histology of the testicles is shown below:

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The upper image is that of the cryptorchid testicle. Interstitial cells (Leydig cells) and germ cells (spermatogonia) are present but there is no active spermatogenesis. In fact the tubules are in greater disarray than expected if one is accustomed to equine cryptorchid histology (another species where cryptorchidism is common).

The lower image shows that spermatogenesis was proceeding to spermiation in some tubule cross sections in the descended testicle. The author was struck by the relative lack of tubule cross sections in which spermiation was occurring.  This may have been associated with the fact that this dog was only seven months old and therefore only on the verge of puberty. Also, besides being sparse, spermatogenesis was not normal in this testicle. Large cells resembling hypertrophic secondary spermatocytes were present in some tubules. Also present were cells that contained extremely compact, basophilic nuclei.  These are shown below:

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Other cells appeared to be binuclear or were in a state of mitosis, a phenomenon not normally visible in seminiferous epithelium:

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The significant of these findings is not certain but again they may be associated with the peripuberal status of this dog.

The prostate gland shown here

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From what can be seen in this interactive histology preparation, of a normal male dog (click on Guest to log in automatically) the glands in this dog were probably inactive i.e. there was no prostatic fluid within the gland in the sections shown above. A word of caution: When one views the cross section of a normal canine prostate gland, it should be noted that secretions accumulate in collecting ducts towards the center of the gland. Therefore it is possible that the sections shown here were too superficial within the gland to show secretions.  My thanks to Dr David Sims, a colleague here at the AVC for that interactive preparation. Incidentally David informs me that the measuring tool was not programmed for that preparation so any measurements will be meaningless.

In summary, no conclusions could be drawn as to the normalcy of the prostate in this dog.

Notes: Cryptorchidism is a common problem in dogs, especially the toy breeds. The mode of heritability is not clear but, in some breeds, it has been associated with an autosomal recessive gene.

The risk of neoplasia in retained testis has been reported to be 9 to 14 times higher than in the scrotal testis with Sertoli cell tumors and seminomas being the most common tumors. Due to the fact that the testicles in dogs do not descend until birth or shortly thereafter, one should not confirm a diagnosis of cryptorchidism until a dog is at 4 months of age, especially in view of the fact that prepuberal testicles are sometimes very difficult to feel in dogs.

Early pyometra or vaginitis

Keywords: pyometra, amoxicillin, antibiotics, cytology, metestrus, vaginitis, bacteria, anatomy, terminology

This image shows vaginal cytology from a three year old Pekingese with a history of a single litter (C-section). This bitch was presented 45 days post estrus with a purulent vulvar discharge. There was no evidence of pyometra on transabdominal US. Therefore this was assumed to be an early or transient case of pyometra or less likely, vaginitis.

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The bitch was treated with amoxicillin for 5 days and the discharge resolved uneventfully. 

This image is presented because of its value in teaching two subjects: i. pyometra ii. the metestrus stage of the canine estrous cycle. With some variation in the number of bacteria present in each case, the cytology is similar i.e. parabasal cells and variable numbers of neutrophils.

Discussion on terminology: 

Should one refer to this condition as a vulvar, vaginal, or a vestibular discharge?

In general, a discharge is named for the orifice from whence it is issued. For example, pus from the uterus may form part of a cervical or vulvar discharge, two orifices from which it is usually observed. The vagina is a tube that connects those two orifices (the cervix and vulva) and is not an orifice itself from whence a discharge occurs. Therefore, this author does not support the use of the term "vaginal discharge".

If this pathology was observed as a vulvar (adjective) discharge what does the vulva consist of? Although part of the vulva is visible from the exterior, it extend cranially to the urethra. In fact, the vestibule is recognized as part of the vulva by some authors. Indeed, in humans, it is considered that all tissues caudal to the external urethral opening are parts of the vulva (noun). In veterinary terminology, the vulva is not usually considered to be part of the vestibule although, according to the etymology of the word, vestibule is derived from the Latin term for entrance. Therefore it is merely a matter of how long one considers the entrance to be and in a comical sense, does it include the front door (the vulva) or not? Rather laboriously then, it appears to be most correct to refer to the external observation in this case as being: "A discharge from the vulvar lips". With regard to the finding of the same discharge in the vagina, the condition should be referred to as "A cervical discharge". 

Selected references

Nguyen J, Duong H 2020. Anatomy, Abdomen and Pelvis, Female External Genitalia  . StatPearls Publishing, Treasure Island (FL).

Schlafer D.H. and Foster R. A. 2016 Jubb, Kennedy & Palmer's Pathology of Domestic Animals: Volume 3. : 358–464. Female Genital System

 

 

Assessment of the prostate gland; transrectal palpation

Keywords: canine, dog, prostate, radiology, hyperplasia, neoplasia, palpation

The canine prostate gland is frequently affected by hyperplasia, cystic development, infection and neoplasia.

Using ultrasonography for measurement (the gold standard in this regard), the size of the prostate in a 15 kg dog is approximately 3.4 cm long and 2.8 cm dorsoventral and 3.3 cm in diameter. There is however, a highly significant correlation between body size and the size of the prostate gland.  An accurate assessment of size can be calculated by using a formula for volume of an ellipsoid i.e. volume = length x width x height x 0.523. For details, refer to Ruel et al. 1998. Ultrasonography is also very valuable in detecting prostate pathology.

Before ultrasonography or any other procedures (radiology, flushing, cultures etc) are performed, the prostate should always be examined by transrectal palpation. Palpation of the prostate (Figure 1) is also a routine practice in breeding soundness evaluations and is used to collect prostate fluid samples to diagnose prostatitis.

Figure 1. Transrectal Palpation of the canine prostate. Note how one hand is used to push the prostate in a dorso-caudal direction while a finger on the other hand is used transrectally to assess prostate size, regularity and sensitivity. Pain may indicate infection or neoplasia.

The prostate is an ovoid-spherical structure that surrounds the urethra just distal to the bladder. It is bi-lobed and has both a dorsal and ventral sulcus, only the dorsal sulcus being palpable. The prostate gland is far smaller in castrated dogs than intact dogs, shrinking to castrate size within 6 months at most. Therefore neoplasia or other pathology should be suspected if the prostate is enlarged or irregular in castrated dogs.

Selected references:

Barsanti, J. A. and Pineo, D. R. 1986. Canine prostatic diseases.  Vet Clinics of North America:Small animal practice. 16: 587-599

Ruel, Y. et al. 1998. Ultrasonographic evaluation of the prostate in healthy intact dogs. Vet Radiol. Ultrasound 39: 212–216.

Smith, J.   Canine prostatic disease: A review of anatomy, pathology, diagnosis, and treatment, Theriogenology 70 (2008) 375–383

Pyometra: post euthanasia in a bitch

Keywords: canine, pyometra, postmortem, euthanasia.

Figure 1. Pus filled uterus from an adult bitch. Copyright. Dr Holly Munroe (munroeholly@hotmail.com).  Size: 978 x 738 px

A ten year old nulliparous intact female boxer x hound presented with a vague history of being in heat "earlier that year".  She was restful and alert but thin; in poor body condition. Despite a history of inappetence the bitch had a ravenous appetite on presentation  Her abdomen was distended and tender on palpation. There was no vulvar discharge.

Trans abdominal ultrasonography revealed large, echogenic, fluid-filled structures, suggesting pyometra. The owner elected not to treat the bitch but allowed post mortem examination. That examination revealed a grossly enlarged uterus filled with red-tinged purulent fluid.  Handling of the uterus allowed un-twisting of segments of the uterus and produced a vulvar discharge consistent with the uterine fluid. Absence of of any vascular embarrassment on the twisted uterus suggested that the twists were postmortem artifacts and the pyometra had indeed been "open".

For additional images of canine pyometra  please see these entries in LORI:

• Pyometra
• Pyometra in a five year old Newfoundland bitch
• Aglepristone treatment for pyometra

Schistosoma (schistosomus) canine fetus

Keywords: schistosoma, canine, fetus.

Schistosoma literally means "split body".  The adjective schistosomus describes the noun schistosoma. The term schistosoma reflexus is often used incorrectly because the body wall is not reflected in all cases of schistosoma. In fact, other than in cattle, schistosoma reflexus is comparatively rare.

During the formation of the embryo, it folds inward on its ventral surface, as shown in this video. That process forms the gut from the endoderm. The umbilical cord is formed and the yolk sac, depleted in the process. On rare occasions, closure of the peritoneal cavity at the umbilicus is not complete. This allows the intestines and other viscera to lie free in the amnion.

The image below shows a case of schistosoma with evisceration in a canine fetus.

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Schistosoma has been described in many mammals, including humans. Affected fetuses may live until term or be born live; usually by cesarean section. The condition has been particularly well described in cattle where it is indeed one of schistosoma reflexus; a cause of dystocia.

Schistosoma is thought to be heritable; at least in some cases. Indeed, abnormal karyotypes have been demonstrated in some cases in various species. In one report, an entire litter of puppies was affected, reflecting either a chromosomal or epigenetic etiology. However, its not clear to this author if the condition is always to be regarded as heritable and as a basis on which to cull animals from breeding programs. Clearly more knowledge is required in this regard.

Selected references:

Atasever, A. et al. 2015.A case of report Schistosoma reflexum in the 12 fetuses of Belgian Malinois dog. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 21: 937-941

Ozalp, G.R. 2011. A case of schistosoma reflexum in a cat with chromosomal aberrations. Reprod. Domestic Animals. 46: 373-376

Persistence of the Müllerian ducts

Keywords: Canine, persistent, Müllerian, uterus, ductus deferens, testis, histology

At the outset. the author wishes to thank Dr Natalie Fraser of the University of Queensland for recognizing this case as being unique, performing the karyotype and bringing the case to the attention of the author. Furthermore, the author must thank both Drs Fraser and Xavier Schneider for making material available for histology. Please see their contact information below the references in this entry. Except for the histology, copyright for all images belong to Drs Fraser or Schneider.

A 2 year old Kelpie was presented for self-mutilation of ambiguous external genitalia. As shown below, a short penis protruded from between the vulva lips, a urethral opening being present at the end of that structure. Urine flowed from this opening.

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A radiograph of the structure showed that it contained a small os-penis (see below). Therefore, the structure was considered to be a hypoplastic penis.

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During gonadectomy, testicle-like structures were noted. These structures had adnexa resembling epididymides (see below). However, the tubular genital tract resembled a uterus, not the expected ductus deferentia. The tubular tract on either side approached fusion at the caudal extent of the operative field, even showing evidence of a structure resembling an intercornual ligament. However, it was impossible to identify fusion into a uterine body or cervix.  Nevertheless, the structure was presumed to be a uterus. A prostate gland was not described. During the operation, other tubular structures adjacent to the uterine horns were not remarked upon. It was only during histological examination that it was evident that ductus deferentia had been present, lateral to the uterus. In retrospect, they could have been seen macroscopically (see below). Because only one section of the uterus was obtained for histology, it is not known if  the ductus deferentia were complete on both sides.

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The image below shows that two structures were present in the section of the tubular genital tract retained for histology. Clearly, a ductus deferens was present in this section and medial to it, a section of a uterine horn. Recall that the male or wolffian (mesonephric) system normally develops lateral to the müllerian or female (paramesonephric) system in embryos. Therefore this finding was consistent with normal early embryogenesis. Later in gestation of course, the uterus regresses in normal males. This is discussed later.

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A cross section of the ductus deferens is shown below. It contained pseudostratified, ciliated epithelium and thick layers of inner circular and outer longitudinal smooth muscle; seemingly normal for a ductus deferens in every respect.

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Uterine histology revealed endometrial gland development that was simple and sparse but otherwise, surprisingly normal in appearance. Adrenal progesterone production may have stimulated gland development to some degree but hypoplasia of the lamina propria was no doubt due to the a relative absence of progesterone; otherwise augmented by corpora lutea.

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Four tissue sections of one of the gonads were examined and no ovarian tissue was noted. This gonad contained only seminiferous tubules and was therefore, a testis. Spermatogenesis was completely absent; a situation that is to be expected in all cryptorchid testicles. Naturally, the epididymis was devoid of spermatozoa as well.

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Unfortunately only one gonad was examined histologically, leading one to assume that the contralateral gonad was also a testis. There is of course, the possibility that the unexamined gonad was an ovotestis. In such a case, the animal would be referred to as a "lateral, true hermaphrodite" but those individuals are rare. Therefore it may be safe to assume that both gonads were testes. That being the case, this dog would properly be referred to as a pseudohermaphrodite because the gonads were of one sex and the remainder of the reproductive tract was ambiguous. In addition, because the gonads were testes, this dog would most accurately described as a male pseudohermaphrodite (Female pseudohermaphrodites are extremely rare). 

With persistent mullerian ducts, this male pseudohermaphrodite potentially belonged to one of two syndromes where mullerian ducts persist into adulthood in male animals. In the author's opinion, both can correctly be referred to as persistent mullerian duct syndromes (PMDS) i.e.

1. PMDS is found in males with testes and XY karyotypes. This is the form of PMDS commonly described in veterinary medicine; adopted from the description in humans.. It is inherited as a dominant autosomal trait. A male cat with PMDS is described in the Feline section of LORI. Mullerian ducts have been shown to persist in male animals even though anti mullerian hormone (AMH) is being produced, probably a result of a defective receptor site or its downstream intermediaries. Indeed, this appears to be the de facto case in dogs with PMSD. The mullerian system is presumed to be insensitive to AMH in such individuals. 

2. PMDS may also be found in so called "sex reversed" XX males. The term "sex reversed" suggests that the reproductive tract is the complete opposite of what is expected according to the karyotype. However, this is seldom the case. Indeed, the phenotype of the XX reproductive tract varies greatly in XX animals. Some are obviously male-like, while others are so mildly androgenized (with small populations of seminiferous tubules in their ovaries) that pregnancy is possible. Therefore the author prefers the term "XX pseudohermaphrodite" because it covers the range of genital tract phenotypes that can occur in these individuals. In rare cases, XX animals with PMDS are true hermaphrodites i.e. their gonads have germinal tissue from both sexes; all the more reason not to refer to these animals as "sex reversed".

As mentioned earlier, the mullerian system develops by default in embryos i.e. if the gonads (male or female) are removed from an embryo, the mullerian system will persist and form the cranial vagina, the cervix and the uterus. Alternatively, if an embryo has testes, sertoli cells are present, causing apoptosis and regression in the mullerian system. 

In dogs with PMDS (of both types) AMH is produced by the Sertoli cells yet it does not suppress the mullerian system. In dogs, it has not been determined if insensitivity to AMH is due to aberrations in the molecular structure of AMH, abnormalities of AMH receptors sites or translation of AMH effects within target cells.  In the image below, it is obvious that a substantial population of sertoli cells was present in the testis of this dog. Although serum concentrations of AMH were not measured, published data suggest that AMH was probably being produced. 

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A partially developed penis and os penis suggests that the leydig cells in the testes were indeed producing testosterone.

The presence of well developed wolffian ducts (ductus deferentia) lateral to the uterus was interesting but not unexpected because of the presence of testes. In fact, the wolffian system can be so well developed in some XY males with PMDS, that they can be fertile. Certainly, this has been described in humans. 

The karyotype of  dogs with classic PMDS is usually 78XY with the cause of PMDS located to an autosomal recessive gene. Initially, the author made a diagnosis of  classic PMDS in this case. However, the karyotype in this male was later found to be 78XX. See below. 

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This indicated that the persistence of mullerian ducts in this dog was not related to the autosomal gene abnormality described in the classic persistent mullerian duct syndrome. The cause of PMSD in dogs with XX karyotypes is unknown. 

To describe this case as being one of "PMDS in a dog with XX sex reversal" would be incorrect. With testes and a mixture of both male and female tubular genital tracts, its phenotypic sex was certainly not reversed. 

PMDS is usually discovered at surgery and affected males are often cryptorchids; unilaterally or bilaterally.  As expected, cryptorchid testes in these cases occasionally become neoplastic.

Selected references:

Belville, C. et al 1999. Persistence of mullerian derivatives in males. Am. J. Med. Genet.89:218–223.

Berkman, F. 1997. Persistent mullerian duct syndrome with or without transverse testicular ectopia and testis tumours. British J. Urology. 79:122-126

Hagjer, S et al. 2015 Intra-abdominal seminomas in bilateral undescended testes in a patient with persistent mullerian duct syndrome. Hellenic J. Surgery 87: 493-496

Haibel, G.K. and Rojko, J.L. 1990. Persistent Miillerian Duct Syndrome in a Goat. Vet Pathology. 27:135-137

Kaore A et al 2012. Persistent Mullerian Duct Syndrome NJIRM.3: 153-154

Knebelmann, B. et al 1991. Anti-Mullerian hormone Bruxelles: A nonsense mutation associated
with the persistent Mullerian duct syndrome. Proc. Natl. Acad. Sci. 88:3767-3771

Leocadio, D. E., et al. 2011. Anatomical and histological equivalence of the human, canine, and bull vas deferens. Can. J, Urology 18: 5699-5704

Meyers-Wallen, V.N. et al 1989. Müllerian inhibiting substance is present in testes of dogs with persistent mullerian duct syndrome. Biol. Reprod. 41:881-888

Meyers-Wallen, V.N. et al 1993. Mullerian inhibiting substance is present in embryonic testes of dogs with persistent mullerian duct syndrome. Biol. Reprod. 48:11410-1418

Nayak, V.J. et al 2014. Persistent mullerian duct syndrome: A case report and review of the literature. Int J Appl Basic Med Res. 4:125–127

Schulman, J. and Levine, S.H. 1989. Pyometra involving uterus masculinus in a cat
J Am Vet Med Assoc.194: 690–691

Weissbach, L. et al. 1999, Prognostic factors in seminomas with special respect to hCG: results of a preospective multicentric study. Eur Urol. 36:601-608

Meyers-Wallen, V.N. 2009. Review and Update: Genomic and Molecular Advances in Sex Determination and Differentiation in Small Animals. Reprod.Dom.Anim. 44:40–46

Verma, R.S. 1996 Genetics of Sex Determination. ISBN-10: 1559388366

Wu, X et al. 2009. A single base pair mutation encoding a premature stop codon in the MIS type II receptor is responsible for canine persistent Müllerian duct syndrome
J.Andrology, 30: 46-56

Contact information and acknowledgements:  

Dr Natalie Fraser (natalie.fraser@uq.edu.au)

Dr Xavier Schneider (Xavier.Schneider@qldvetspecialists.com.au )

Thanks to Dr Herris Maxwell (maxwehs@auburn.edu) for raising the valid point that this dog could have been an XX male pseudohermaphrodite ("sex reversal"). The author had originally presumed it to be an XY male pseudohermaphrodite; a classic PMDS.

The author extends his thanks to L.Dobbin of the Diagnostic Quality Assurance Program at the AVC for allowing the use of their excellent Olympus BX6 1VS virtual microscopy equipment. For more information on the creation of virtual histology on the internet (soon to be featured on LORI) contact Ms Dobbin at 1-902-0831 or edobbin@upei.ca

A true intersex (hermaphrodite) dog

Keywords: intersex, DSD, true, hermaphrodite, canine, dog, nomenclature

This entry relates to a dog presumed to be female when it was born. At ten months of age, the animal experienced discomfort due to abrasion of a penis-like mass protruding from the vulva lips. The mass, and two intra-abdominal gonads were removed surgically. No tissue was available from the tubular reproductive tract and its anatomy was not described. The author only had access to cut and stained histological sections of the gonads. Also, the history did not state which gonad had been sampled histologically or if both gonads had been similarly affected.

In the histology of gonad seen here, seminiferous tubules devoid of active spermatogenesis can be seen at upper left. Only sertoli cells were present in these tubules. In the same inset image, a large tertiary (graafian) follicle is seen. In the smaller inset image at lower magnification, seminiferous tubules are seen again, adjacent to a group of cortical follicles in various stages of development.

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This polyovular follicle and several others were seen in this gonad. Polyovular follicles are common in normal dogs and cats. Up to seven oocytes have been seen in a single follicle. 

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Discussion.
If both gonads had contained male and female elements in this patient (most likely) it would be referred to as a bilateral, true hermaphrodite. If only one gonad was affected, the term lateral true hermaphrodite would have been used. Usually the rest of the genital tract is ambiguous in true hermaphrodites.

It should be noted that the terms "hermaphrodite" and "sex-reversed" are being discarded (especially in human medicine) in favor of less offensive, more modern and descriptive nomenclature. New terminology falls under the umbrella of "Disorders of  sexual development" (DSDs) with specific annotations pertaining to the condition added after DSD. In this case for example, the animal would be referred to as having a DSD with bilateral ovotestes and ambiguous genitalia. If the karyotype and SRY status were known, they would be added to the description. The author acknowledges the value of these changes but believes that the terms hermaphrodite and pseudohermaphrodite (pseudo-hermaphrodite) are valuable descriptors and should not be abandoned in veterinary medicine. At risk of reprimand, their use continues in this entry.

True hermaphroditism is occasionally seen in humans and of course, in many animals as well, including wild species. The author encountered a report of true hermaphroditism in a Beluga whale; all the more interesting because the ovarian and testis elements were separate from one another and that situation occurred bilaterally.

Most cases of true hermaphroditism in humans and dogs are associated with XX karyotypes. In some of these, translocated SRY sequences occur on the X chromosome or elsewhere, explaining the presence of testes tissue. In most cases however, the SRY sequence is absent. It is presumed that testes determining pathways distal to SRY must be active in such cases. In true hermaphrodites with XY karyotypes, defects in the SRY gene have been detected. As expected, where mutations of the SRY sequence were severe, no testes tissue developed at all. Those individuals developed ostensibly normal ovaries.

The true hermaphrodite condition is complex and still poorly understood. Just how complex and intriguing, is illustrated by a case of an American Cocker Spaniel with ovotestes and a normal 78, XX karyotype (Seldon et al, 1978). Despite the presence of ovotestes, this animal had given birth to three pups. One was dead and not karyotyped. Of the remaining two pups, one was an apparently normal 78,XX female and the other, a unilaterally cryptorchid male with an ambiguous genital tract and a 78, XX karyotype.

Selected references.

Braun, A. 1993. True hermaphroditism in a 46,XY individual, caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY) :molecular genetics and histological findings in a sporadic case. Am.J. Hum. Genet. 52:578-585

De Guise, S. et al. 1994. True Hermaphroditism in a St. Lawrence Beluga Whale (Delphinapterus leucas). J. Wildlife Diseases.30:287-290.

Dreger, A.D.et al. 2005. Changing the nomenclature/toxonomy for intersex\; a scientific and clinical rationale. J. Pediatric Endocrinol. Metab. 18:729-733

Hubler, M. et al. 1999. Sry-negative XX true hermaphrodite in a basset hound. Theriogenology. 51:1391-1403

Kousta, E. et al. 2010. Sex determination and disorders of sex development according to the revised nomenclature and classification in 46,XX individuals. Hormones. 9:218-231

McElreavey, K. et al. 1992. A minority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY. Human genetics. 90:121-125

Meyers-Wallen, V.N. et al. 1997. Sry-negative XX true hermaphroditism in a Pasa Fino horse. Equine Vet J. 29:404-408

Meyers-Wallen, V.N. 2006. Genetics, genomics, and molecular biology of sex determination in small animals. Theriogenology. 66:1655–1658

Meyers-Wallen, V.N. 2009. Review and Update: Genomic and Molecular Advances in Sex Determination and Differentiation in Small Animals. Reprod.Dom.Anim. 44:40–46

Pérez-Gutiérrez, J.F. 2015. Bilateral Ovotestes in a 78, XX SRY-Negative Beagle Dog. J. Am. Anim. Hosp. Assoc. 51:267– 271

Selden, J.R. et al 1978. Genetic Basis of XX Male Syndrome and XX True Hermaphroditism: Evidence in the Dog. Science, 201: 644-646

Sommer, M.M  and Meyers-Wallen, V.N. 1991 XX true hermaphroditism in a dog.  J. Am. Vet. Med. Assoc. 198:435-438