LORI.caprine

Polled intersex syndrome

Keywords: goat, caprine, PIS, AMH

Polled intersex syndrome (PIS) is a classic condition, known to all veterinary students. This is because it is controlled quite simply, by advising clients to use a horned buck for breeding. That is because PIS is associated with the polled gene and when a goat is homozygous for the polled gene, PIS is likely to manifest itself. The polled gene is also dominant, therefore a buck will be polled even if it is heterozygous for the polled gene. The corollary is that the polled gene cannot be inherited by a kid if the herd sire has horns. It also means that even if the doe bred to the horned buck is either hetero- or homozygous for the polled gene, the fetus cannot be homozygous for the polled gene and will not manifest PIS.

The following images (more that 40 years old but still valuable) show the reproductive tract of a PIS goat. It should be mentioned that there is no "typical" manifestation of PIS therefore these image cannot be regarded as typical.  Some goats are highly feminized, others very masculine. This is an extreme manifestation of PIS.

Figure 1. The ambiguous external genitalia of a polled intersex male. The testes are visible in the flattened scrotum. Image size: 500 x 726px

Figure 2. The internal genitalia of the animal shown in figure 1. Note the almost complete suppression of the paramesonephric (mullerian) system (uterus and cervix) . The mesonephric (wolffian) system is visible on either side of the paramesonephric system. Also note the urogenital sinus, a part of the tubular system that would have developed into the vagina in a female. There is no cervix; a part of the paramesonephric system completely suppressed by AMH. Image size: 1091 x 894px

Testes are invariably present in the PIS syndrome. External genitalia can be female in appearance, male-like or as was the case here, ambiguous. In many cases they are not "sex-reversed" or male pseudohermaphrodites because the testes and the rest of the genital tract are congruent.

This male had a müllerian system that was severely suppressed. This is not surprising because anti müllerian hormone (AMH)* is produced by the testes in PIS goats. The testes in PIS goats usually have no spermatogonia but do have both sertoli and leydig cells; the former being a source of AMH, the latter, a source of testosterone. With regard to testosterone, it is not surprising then, that PIS goats are often strongly masculinized and used as teaser males. The testes may descend in some PIS goats but more often, they are cryptorchid (as was the case here). As is occasionally the case with cryptorchid testes, they can become neoplastic.

Figure 3. Scrotum of a suspect intersex male goat. This male was infertile, producing no sperm when electro-ejaculated. He had a small scrotum, small testicles and was polled. Therefore it was presumed that he was homozygous polled and an intersex goat. Image size: 768 x 564px

Notes The genetic cause of PIS is extremely complex. The dominant gene for polledness and the recessive gene for PIS appear to lie close to one another on chromosome #1. There is thought that they might even be the same gene with pleiotropic functions. This abnormality is associated with the absence the FOXL2 and PISRT1 genes in PIS goats. These genes (and others) are present in normal females, coding for the development of ovaries. In their absence, testes develop. Therefore it is not the mere presence of the SRY, SOX9 and downstream genes that code for testes development; the absence of FOXL2 and PISRT1 is also important. In fact, even though SOX9 is present in female goats, its expression is usually inhibited by PISRT1. However, if PISRT1 is absent, SOX9 will be expressed and testes will develop, even though SRY is not present. These facts are important to bear in mind when one contemplates how it is possible for an animal with a normal 60 XX karyotype to have testes, especially if it is SRY negative. Indeed, that is the case in all goats with PIS.

* Also known as müllerian (mullerian) inhibiting hormone (MIH) or müllerian inhibiting substance
 (MIS).

Selected references:

E. Pailhoux, E. et al 1994. Molecular analysis of 60,XX pseudohermaphrodite polled goats for the presence of SRY and ZFY genes. J Reprod. fert. 100491-496

E. Pailhoux, E. et al 2005. Positional cloning of the PIS mutation in goats and its impact on understanding mammalian sex-differentiation. Genet. Sel. Evol. 37 (Suppl. 1):S55–S64

E. Pailhoux, E. et al 2002. Ontogenesis of female-to-male sex-reversal in XX polled goats. Developmental dynamics. 224:39-50

Boulanger, L. et al. 2014. FOXL2 Is a Female Sex-Determining Gene in the Goat. Current biology. 24:404-408

King, W.W. et al. 2002. Multiple congenital genitourinary anomalies in a polled goat. Contemporary topics: American society of animal science. 41:39-42

Li, X. et al. 2011. Special variations within 11.7 kb fragment in goat polled intersex syndrome. African journal of biotechnology. 10:6695-6699.

Schibler, L. et al. 2000. Fine Mapping Suggests that the Goat Polled Intersex Syndrome and the Human Blepharophimosis Ptosis Epicanthus Syndrome Map to a 100-kb Homologous Region Genome research. 10:311-318

Yokata, S. et al. 2011. Polled Intersex Syndrome with Urethral Atresia in a Goat J. Vet. Med. Sci. 73: 1355–1357