Theriogenology Question of the Month

Lisa K. Pearson Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

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Jacobo S. Rodriguez Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

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Ahmed Tibary Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

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History

A 4-year-old Holstein cow from the Washington State University dairy was artificially inseminated 2 times during her second lactation. Pregnancy was diagnosed via transrectal palpation and confirmed with ultrasonography 33 days after the second artificial insemination. One fetus with an apparently normal heartbeat was detected during ultrasonography. The pregnancy was confirmed at 75 and 185 days of gestation via transrectal palpation, and the cow calved after a gestation of 291 days. A clinically normal healthy calf was born, which was followed by the expulsion of a separate mass of hair-covered fetal tissues (Figure 1). The fetal tissues were submitted to the Theriogenology Service at Washington State University for evaluation.

Figure 1—
Figure 1—

Photograph of a hair-covered fetal mass that was expelled after the birth of a healthy Holstein calf. There is a cystic dilatation in the ventral aspect of the fetus and a placental attachment projecting caudally. Bar = 30 cm.

Citation: Journal of the American Veterinary Medical Association 238, 10; 10.2460/javma.238.10.1261

The mass measured approximately 30 × 20 × 15 cm (12 × 8 × 6 inches) and weighed 4.41 kg (9.7 lb). It was ovoid in shape, and approximately 80% of its surface was covered in black and white hair. It was asymmetric with a suggestive cranial-caudal orientation, and there were anatomic structures similar to a tail and anus at the caudal end. A 10-cm-diameter fluid-filled cystic structure was evident on the ventral aspect, near the location at which fetal membranes exited the mass. All fetal membranes were not submitted for examination.

Question

What is the most likely diagnosis for the fetal mass? Please turn the page.

Answer

Globosus amorphus, also called acardiac acephalic twin or acardiac amorphous twin.

Results

The globosus amorphus described here did not appear to have negative effects on the cow or live-born twin. Initial reports from personnel at the dairy indicated that the healthy live-born twin was a heifer. Our hypothesis was that this heifer calf might be a freemartin if the globosus amorphus was male with tissues that produced anti-Müllerian hormone during early gestation. To investigate this hypothesis, a full-thickness skin biopsy specimen was obtained from the globosus amorphus and submitted to the Molecular Cytogenetics Laboratory at Texas A&M University for cytogenetic analysis of tissue fibroblasts; that analysis revealed a normal male chromosome complement (60,XY).

Advanced imaging techniques were used to determine the amount of organogenesis and tissue organization in the globosus amorphus. Radiography, computed tomography, and magnetic resonance imaging (Figure 2) revealed 4 amorphous ossified structures, which were suggestive of vertebrae, but no identifiable organs. The globosus amorphus was sectioned and freeze dried for preservation.

Figure 2—
Figure 2—

AT1-weighted coronal magnetic resonance image of the fetal mass in Figure 1. Notice the poor differentiation and organization of the tissues. Several small bones (arrows) are evident in the mass, but there is no evidence of testicular tissue.

Citation: Journal of the American Veterinary Medical Association 238, 10; 10.2460/javma.238.10.1261

At approximately the same time, a visit was made to the dairy to examine the live-born twin heifer calf. However, the initial reports about the sex of that calf had been erroneous; the live-born calf had been a male and was no longer on the premises.

Discussion

Globosus amorphus is a result of embryonic maldevelopment most often recognized in humans pregnant with monozygotic twins, although this condition has been reported in veterinary species pregnant with dizygotic twins. Globosus amorphus has been sporadically reported in several domestic animal species, including goats, sheep,1 horses, and cattle.2,3 Cattle appear to represent the highest number of described cases, although this condition is almost certainly underreported because of the unique features that distinguish this condition in veterinary species from that which occurs in humans.

It is estimated that 1 in 35,000 human pregnancies results in an acardiac twin,4 and this represents < 1% of all monozygotic twin pregnancies.5 In human medicine, the nonamorphous twin is commonly referred to as the pump twin because it provides vascular perfusion to the acardiac twin through a process called twin-reversed arterial perfusion. In this process, deoxygenated blood from the pump twin does not return directly to the dam through the placenta; instead, that blood perfuses the acardiac twin through placental arterial anastamoses before returning to the maternal circulation. The acardiac twin is perfused in a retrograde manner, and the iliac vessels are perfused first, which leads to development of the caudal extremities and organs, if present.6 In all species, there is a 100% mortality rate for the acardiac twin. In humans, the pump twin has a high rate of congenital defects (most notably congestive heart failure or hydramnios) or preterm parturition, and the reported mortality rate for the pump twin is 50% to 75%.4

In contrast to the high rate of congenital defects seen in human twins, the authors are not aware of reports of developmental anomalies in fetuses cotwin or cotriplet to a globosus amorphus in the veterinary literature. Most reports of globosus amorphus in domestic animal species have indicated the birth of healthy viable neonates, except in cases of prolonged dystocia. Therefore, the issue is raised as to the differences in veterinary species that account for no effect of a globosus amorphus on the cotwin. There are 2 major hypotheses for the reason that domestic animal species do not have the same rate of congenital defects in fetuses born cotwin to a globosus amorphus as humans do.

The first hypothesis involves the fact that pregnancies with multiple fetuses in veterinary species are almost always the result of multiple ovulations. Rarely have cases of monozygotic twin pregnancies been reported in domestic animals; typically, such cases have been in cattle or horses.7 Humans are one of the only species in which monozygotic twin pregnancy is a common feature. Monozygotic twin pregnancy is achieved by spontaneous division of the fertilized ovum or early embryo. Splitting of embryos of domestic animals has been achieved ex vivo in laboratory settings and has resulted in genetically identical offspring when successfully transferred into recipient dams. Additionally, twin pregnancy resulting from embryo transfer of 1 embryo has been reported in several horses,8 and globosus amorphus was reported after embryo transfer in a cow.3 Monozygotic twin pregnancies are thought to arise from damage to the zona pellucida during collection, manipulation, and transfer of a single embryo and may be responsible for the development of the amorphous fetus. This highlights the importance of ultrasonographic examination of a recipient mare in an embryo transfer program at 14 to 17 days after ovulation. In cattle, the window for diagnosis is far less crucial because this species physiologically has a high rate of twin pregnancies that are carried to term. In horses with monozygotic twin pregnancy, the end result is early embryonic death or abortion.7,8 The fact that domestic animal species do not commonly develop monozygotic twin pregnancies means that the cleavage step that results in 1 embryo forming 2 embryos is absent, thereby reducing the chance of cleavage errors that may occur and result in congenital anomalies. Therefore, a fetus that is cotwin to an amorphous fetus is independent from the developmentally abnormal amorphous fetus, which explains the lack of congenital defects associated with this condition.

The second hypothesis for the reason that domestic animals have no congenital abnormalities in fetuses cotwin to an amorphous fetus is that the type of placentation plays a crucial role in blood flow between the fetuses. Humans have hemochorial discoid placentation, whereas ruminants have epitheliochorial cotyledonary placentation and equids have epitheliochorial diffuse microcotyledonary placentation. In humans, the amorphous twin is perfused with deoxygenated blood from the viable fetus via twin-reversed arterial perfusion as a result of arterial anastomoses within the placenta. Although not definitively confirmed, it is likely that this perfusion does not occur to the same degree in domestic animals because each dizygotic twin would have its own placenta. However, the authors of a report1 of a globosus amorphus in a sheep described the classic characteristics of caudal development (including the hind limbs, vertebral column, and rib cage); the forelimbs were poorly developed, and the fetus was acephalic. That report may have represented perfusion of the fetus in a retrograde manner, similar to blood flow reported in humans with acardiac twins. The bovine amorphous fetus reported here had its own placental attachment; however, all fetal membranes were not submitted for evaluation, so it is not known whether the globosus amorphus and live-born calf had placental arterial anastomoses.

One factor hypothesized to be involved in the pathogenesis of cardiovascular anomalies (eg, hydrops fetalis or congestive heart failure) in the pump twin in humans is the ratio of weight between the fetuses. The larger the amorphous twin, the harder the cardiovascular system of the viable fetus must work to supply blood for both fetuses, which leads to abnormalities in fluid distribution. To our knowledge, these effects have not been reported in veterinary patients.

In cattle, a dizygotic pregnancy resulting in a live heifer calf and a nonviable male acardiac twin has been reported.2 Cytogenetic analysis of the female calf by use of fibroblast and leukocyte cultures revealed a normal female karyotype (60,XX), whereas fibroblast culture of the amorphous fetus revealed a normal male karyotype (60,XY). It has been estimated that in 92% of twin pregnancies in cattle that result in 1 male and 1 female, the female twin will display signs of freemartinism. In the aforementioned report,2 the female calf was anatomically normal at birth, although no examinations were performed after the heifer reached puberty. It is not known whether the androgen-producing tissues of the nonviable male acardiac twin were developmentally normal; it is possible that the heifer was not subjected to the in utero effects of masculinization because there were developmental aberrations of the male cotwin.

In the present report, the viable and nonviable fetuses were both male. Initial reports from the dairy indicated that the viable calf was a female, which led to the use of advanced imaging techniques and chromosomal analysis to determine the sex of the acardiac fetus. Our hypothesis was that if testicular tissue were present in the male acardiac twin, it would have caused freemartinism in the viable heifer calf. No testicular tissues were identified via gross examination or the use of advanced imaging techniques of the amorphous fetus, and subsequent communication with the dairy personnel revealed that the viable calf was a male.

Differential diagnoses for a globosus amorphus include a teratoma or mummified fetus. Examination of the fetal tissues is necessary to provide a definitive diagnosis. A globosus amorphus is characterized by the evidence of fetal membranes and a cranial-caudal fetal orientation.

Developmental anomalies in a fetus should not be disregarded. Examination of affected fetuses can advance our understanding of these aberrations. Studies are needed to evaluate the role of placentation and monozygotic versus dizygotic twin pregnancies in the development of globosus amorphus in domestic animals.

Outcome

The cow developed cystic ovarian disease after parturition. However, she was successfully treated and subsequently was artificially inseminated. At 116 days of lactation, she was confirmed pregnant (day 28 of gestation) via ultrasonography. She gave birth to healthy twin calves after an uncomplicated gestation.

References

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  • 3.

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