Freemartinism
Keywords: Freemartin, bovine, infertilityThe image below shows the reproductive tract from a freemartin heifer. Although there is great variation in the manifestation of Freemartinism, this tract show some characteristics that are common to many of these animals.
Image size: 1000 x 557px
Note how the development of the müllerian tubes (precursors of the cranial vagina, cervix, uterus and uterine tubes) was suppressed by anti-müllerian hormone (AMH). AMH was presumably produced by the small gonads seen here where ovaries are usually found. Although it was not verified histologically in this case, these gonads would have contained cells from the male co-twin, including Sertoli-like cells that produce AMH. Of course, it is normal for a male fetus to produce AMH because the müllerian system must be suppressed if the male is to develop normally. However, in female fetuses where the gene for AMH production is inactive, AMH production by the gonads is disastrous.
As alluded to above, gene coding for AMH production is active in the male co-twin. Therefore gonadal cells derived from the male produce AMH in the co-twin's (Freemartin) gonad. In addition, AMH from the male twin circulates in the female co-twin, amplifying the suppressive effect on the female tract. That has occurred here; the uterus is a mere thread, the cervix is absent and the cranial vagina is also absent. The caudal vagina develops from the ectoderm in a fetus, a system that is not affected by AMH, so it is virtually normal in Freemartins. In this image, a probe has been inserted into the vagina, demonstrating the presence of a normal vestibule i.e. cranially, up to the level of what would have been the hymen. More cranial to that, normal tract is almost absent.
As discussed below, there is a considerable range in the manifestation of Freemartinism; the tract may be barely affected or may be extremely masculinized. The specimen shown here would probably be considered modal within that range.
Notes:
In 2005, A.M. Padula published an excellent review of Freemartinism (Padula. A.M. 2005. The freemartin syndrome: an update. Anim. Reprod. Sci. 87: 93–109). For additional detail, one should consult that article and others cited within.
At approximately 28 to 30 days of gestation, the allantochorion membranes of most ruminant co-twins fuse. This causes vascular anastomoses to form between the two conceptuses, resulting in freemartinism, a condition that is especially common in cattle. Freemartins occur in other ruminants, cervids and even pigs. However, the condition is comparatively rare in those species (except perhaps for sheep). This author is not aware of any well-documented case in a horse.
Cellular or humoral influences (or a combination of both) circulate between the two fetuses and effect gonadal development. The earlier the fusion, the more masculinized the female tract will be. In a few cases, the tract is so highly masculinized that it is only slightly ambiguous. The opposite is also true i.e. females can be so mildly masculinized that they are not even recognizable as freemartins, apart from being subfertile.
Interestingly, exchange of cellular material early in gestation also makes freemartins highly tolerant of organ allografts.
Although it is often stated that male co-twins to freemartins are also affected and show deficient spermatogenesis, this is not always so. In fact, males are often completely fertile into adulthood.
On occasion, a male co-twin may die in utero after vascular anastomosis has occurred and although it is unusual (recall that their blood supplies are fused) the female co-twin may survive. In such cases a freemartin may be born as a singlet.
Typically, the müllerian system in freemartins is severely suppressed; in most cases almost impossible to delineate clearly by transrectal palpation (see the image in this entry). This is because the gonads are a mixture of testicular and ovarian tissue, (freemartins are true hermaphrodites). Sertoli cells in the testicular tissue appear to produce müllerian inhibiting factors as they do in normal males. The gonads are also very small and very difficult or impossible to define on transrectal palpation. The vagina of a freemartin is very short (usually less that 12 cm) and it has a blind ending, the cervix being part of the müllerian system.
| Statistically speaking, a female calf born co-twin to a male has approximately a 95% chance of being a freemartin. However one may need further assurance that this is the case. In newborn calves, where a transrectal examination is impossible, this author uses the cover sheath of Cassou artificial insemination pipette as a vaginal ‘depth gauge’. The sheath is inserted into the vagina of the suspect freemartin and bent at the level of the vulva lips. A second sheath is inserted into the vagina of a normal calf and bent at the same level. One then compares the length of sheaths to the point at which they were bent. The length of the section of interest is far shorter in the suspect freemartin calf than the normal calf. The only chance of an error with this method is in normal heifer calves that have imperforate hymens. In a farm setting, one may have to wait for a suspect freemartin heifer to reach an age at which she can undergo transrectal palpation safely. |
If a diagnosis of freemartinism is still uncertain after considering the history, palpable findings, and external and internal appearance of the heifer, numerous other tests can be performed, mostly of a genetic nature. Sex chromosome chimerism (xx and xy) is present within nucleated blood cells and contrary to older data, in lower numbers in other cells throughout the body as well.
The origin of the term freemartin (also free-martin) is a subject of great uncertainty. As discussed by J.B. Marcum in the Commonwealth Bureau of Animal breeding and Genetics abstracts in 1974 (42: 227) the term may have originated in 1593 when "Martin" was a word used a England and Scotland for a cow or ox. The etymology of the prefix "Free-" is more obscure, possibly arising as a contraction of 'farrow" meaning a barren or non-lactating cow or perhaps the German term "farre" meaning bull, denoting a cow that was like a bull.
