Reproductive Tract Pathology in Hyperkeratosis

Transcription

1 Reproductive Tract Pathology in Hyperkeratosis of Cattle and Sheep Kenneth McEntee, D.V.M., and Peter Olafson, D.V.M. HYPERKERATOSIS (X disease) of cattle was first observed in May, 1941, in New York State. The disease was recorded in and was described and illustrated in It is due to one or more toxic materials which occur in a processed wheat concentrate, 6 alfalfa pellets, 7 timothy hay, 4 a German wood preservative, 11 and a lubricant. 1 Hyperkeratosis has been produced experimentally by feeding these substances to cattle; it has also been produced by contact with a wood preservative. Disease due to the wood preservative was observed on farms in Germany where the barns had been painted with preservative from a given tank car lot. The processed wheat concentrate is a by-product of a food used for human consumption; however, the toxic agent has been found only in the by-product and we suspect that it represents contamination. Recently, Sikes claimed that he produced the disease by feeding penta-chloronaphthalene. 10 (Chlorinated naphthalenes are added to some automotive and industrial lubricants.) It has been reported 9 that workers exposed to the mists of chlorinated cutting oils develop chloracne. Hyperkeratosis of cattle is ushered in by a rapid lowering of the plasma vitamin A, 3 lacrimation, salivation, depression, anorexia, and loss of condition. As the disease progresses, the skin becomes thick, hard, and wrinkled From the Department of Pathology, New York State Veterinary College, Ithaca, New York. The work described in this paper was done in co-operation with the Bureau of Animal Industry, USDA, under inter-regional agricultural experiment station research on the project entitled "X-disease (Hyperkeratosis of Cattle)." The authors wish to thank Miss Marion Newson for preparing the illustrations for Figs. 11 and

2 Vol. 4, No. 2, 1953] HYPERKERATOSIS OF CATTLE AND SHEEP 129 and practically every organ of the body becomes involved. Papillary proliferations appear on the tongue, oral mucosa, esophageal mucosa, and in the gall bladder and larger bile ducts. Slight fibrosis accompanies proliferation of the smaller bile ducts. The pancreas may become fibrotic and the acini, cystic. The gastric and intestinal glands as well as the renal tubules undergo cystic dilatation. Squamous metaplasia occurs in the interlobular and main ducts of the parotid and submaxillary salivary glands. PATHOLOGY The pathology of the reproductive system was briefly described in a previous paper. 6 The purpose of the present paper is to describe and illustrate the lesions of the reproductive tract more completely. Changes in the reproductive organs have been observed both in naturally-occurring cases and in experimental animals which died or were given euthanasia in various stages of the disease. Thus we were able to follow the sequence of events in the development of the pathology. In young bulls, metaplasia of the seminal vesicles is one of the early manifestations of the disease. The normal seminal vesicular epithelium varies with age in the bull. In the immature animal, the epithelium is pseudostratified, consisting of a layer of round basal cells and a layer of cuboidal to columnar surface cells (Fig. 1). In bulls affected with hyperkeratosis the epithelium gradually undergoes squamous metaplasia and finally keratinizes. In some areas the lumen becomes plugged with keratin, while in others it is filled with pyknotic epithelial cells and leukocytes (Fig. 2). The ampullae, vasa deferentia, and epididymides undergo metaplasia at approximately the same time as the seminal vesicles. The pseudostratified columnar epithelium of the epididymis gradually stratifies, and in some areas the lumen becomes plugged with keratin. Intra-epithelial lumina become numerous in some areas (Fig. 3). The interstitium is infiltrated with diffuse or focal accumulations of lymphocytes, monocytes, and plasma cells. The epididymis becomes so markedly enlarged and hardened that the condition may be diagnosed by palpation in the living animal. The excretory ducts of the prostate and bulbo-urethral glands undergo a less marked metaplasia. In order to check the degree and rapidity of change in the reproductive organs, the right testis and epididymis were surgically removed from a 4-month-old Holstein calf. The calf was then fed toxic material for a period of 30 days. Sixty days after the initial feeding the animal was moribund

3 Fig. l. Normal seminal vesicle from a 16-week-old bull. (X 145) Fig. 2. Seminal vesicle from a 16-week-old bull with hyperkeratosis. (X 145) Fig. 3. EpiFig. 4. Advanced testicular degendidymis with intra-epithelial lumina. (X 145) eration. (X 145)

4 Fig. 5. Dilated endometrial glands. (X 40) Fig. 6. Dilated endometrial glands. (X 145) Fig. 7. Squamous metaplasia of cervix. (X 145) Fig. 8. Ulceration of vulva. (X 30)

5 132 McENTEE & OLAFSON [Fertility & Sterility and was given euthanasia. At this time the left epididymis was markedly enlarged and hardened (Fig. 11). The comparative weights of the testes and epididymides are given in Table 1. The rapid increase in size of the epididymis results from the metaplastic process, whereas the decrease in size of the testis is a reflection of degenerative change. Histologically, testicular degeneration is more difficult to detect in immature than in mature bulls. In the adult testis, germinal epithelium disappears, leaving tubules which are lined chiefly with Sertoli cells. The basement membrane becomes hyalinized (Fig. 4), and a few mononuclear-type leukocytes collect in the interstitium. The relative specificity and rapidity of development of squamous meta- TABLE 1 Right (surgically removed prior to ingestion of toxic feed) Left (examined at time of autopsy) Testis 24.8Gm Gm. Epididymis 5.2Gm Gm. plasia in male reproductive organs persuaded us to change from heifers to bulls as subjects for experimental hyperkeratosis. Hyperkeratosis in the female bovine results in pronounced changes in the ducts of Gartner. Normally, the lining epithelium varies from columnar to transitional. In hyperkeratosis the epithelium changes to stratified squamous, which sometimes keratinizes (Fig. 9). Cyst formation is common. In a normal young heifer, Gartner's ducts are barely visible to the naked eye. In heifers with hyperkeratosis, they stand out as prominent cords. Metaplasia commences at the external os in the cervix and progresses forward. We have observed similar transformations in the cervix of a heifer which had been given stilbestrol over a long period of time, and in cows with cystic Graafian follicles. Moderate dilatation of the endometrial glands is present (Figs. 5 and 6). The ovaries become small and inactive. Mastitis, prolonged gestation, dystocia, retained fetal membranes, and metritis have been reported in cows with hyperkeratosis. 5 Olson et al. have presented evidence that heifers affected with the disease may recover and reproduce. 8 They reported that 94 heifers which survived an outbreak of hyperkeratosis in which 47 out of 150 died recovered and were bred. E:ach calved and no abnormalities of reproduction could be associated with the previous

6 Fig. 9. Gartner's duct plugged with keratin. (X 30) Fig. 10. Keratinized endometrium. (X 40) Uterus from ewe.

7 134 McENTEE & OLAFSON [Fertility & Sterility Fig. 11. Left testis of bull affected with hyperkeratosis. The epididymis is approximately twice normal size. (X 2) disease. Reference was also made to a bull which developed hyperkeratosis as a calf. They reported that this animal was impotent upon reaching maturity. Naturally-occurring cases of hyperkeratosis have not been observed in sheep. However, disease has been produced in sheep by feeding the toxic

8 Vol. 4, No. 2, 1953] HYPERKERATOSIS OF CATTLE AND SHEEP 135 concentrate. 6 The lesions differ in many respects from those in cattle. In sheep poisoned with the toxic feed, there is liver cell necrosis, regeneration, and fibrosis, but no appreciable bile duct proliferation. In the ram there is some testicular degeneration but no metaplasia of the excretory ducts of the testes or the accessory sex organs. In the ewe, the uterus undergoes Fig. 12. Uterus from ewe. Note papillary proliferations in opened hom. (X H~) marked change. The uterine horns become enlarged and firm. The lining is pale, dry, thick, and shaggy (Fig. 12). Histologic examination reveals squamous metaplasia of the endometrial glands with profuse keratinization (Fig. 10). The glands become plugged with keratin, which protrudes into the lumen of the uterus. The cervix is also involved in the process (Fig. 7). The vulva keratinizes and ulcerates (Fig. 8).

9 136 McENTEE & OLAFSON [Fertility & Sterility SUMMARY Bulls with hyperkeratosis have squamous metaplasia of the accessory sex glands and excretory ducts of the testes. Heifers and cows develop metaplasia of the cervix and Gartner's ducts. The ewe, with experimentally-produced disease, has squamous metaplasia of the uterus and cervix. No metaplasia occurs in the reproductive organs of the ram. REFERENCES 1. BELL, W. B. Virginia]. Sc. 3:71, HAGAN, W. A. Report of the New York State Veterinary College. P. 21, HANSEL, W.; McENTEE, K., and OLAFSON, P. Cornell Vet. 41:367, MILLER, R. C.; BoRTREE, A. L., and SHOOK, J. C. School of Agriculture, Pennsylvania State College. Progress Report 69, April, OLAFSON, P. Cornell Vet. 37:270, OLAFSON, P., and McENTEE, K. Cornell Vet. 41:107, OLSON, C., and CooK, R. H. Am.]. Vet. Research 12:261, OLSON, C.; CooK, R. H., and BROUSE, E. M. ]. Am. Vet. M.A. 120:186, ScHWARTZ, L., and BARLOW, F. A. Pub. Health Rep. 57:1747, SIKEs, D. Nashville Tennessean, June 25, WAGENER, K. ]. Am. Vet. M. A.119:133, 1951.