Volume 7 | Issue 1 Article 6

1944 Pseudopregnancy In Dogs A. F. Weber Iowa State College

Follow this and additional works at: https://lib.dr.iastate.edu/iowastate_veterinarian Part of the Small or Companion Animal Medicine Commons, and the Veterinary Physiology Commons

Recommended Citation Weber, A. F. (1944) "Pseudopregnancy In Dogs," Iowa State University Veterinarian: Vol. 7 : Iss. 1 , Article 6. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol7/iss1/6

This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Pseudopregnancy In Dogs

Relation to mammary neoplasms also discussed

A. F. Weber, '44

HE term pseudopregnancy was first nancy."! In most cases the secretion of T used by Ancel and Bouin (1911) to milk is not marked and its excretion into describe an abnormally long luteal phase the lactiferous sinuses is even more rare. of the estrual cycle observed in the rab­ In an article written on the post-estrual bit. Originally the term applied to the changes occurring in the generative or­ condition whereby, following copulation, gans and mammary glands of the non­ no conception would take place, but that pregnant dog, Marshall and Halman2 con­ uterine and ovarian changes similar to clude that pseudopregnancy is definitely those seen in pregnancy would ensue. It a normal phenomenon in the bitch. is now known that pseudopregnancy can Since the pseudopregnant bitch acts nor­ occur in the virgin bitch following estrum mally and since the interval between two when no copulation has taken place. It heat periods is long enough that the suc­ should be remembered that unlike the rab­ ceeding heat period is not interfered bit, ferret and other animals, the dog with, this condition in most instances es­ ovulates spontaneously, i.e., without the capes the attention of the owner. How­ need of the copulation stimulus to cause ever, the accompanying mammary growth the rupture of the follicle and consequent and development is evident. The amount liberation of the ovum. of lactation present varies, but in some cases is so marked that the owner consults Index for Classification a veterinarian. Frequently there may To classify the various types of pseudo­ develop an inflammatory swelling. A re­ pregnancy, it is suggested that the duration cent case presented at the small animal of the condition and the changes in the clinic at Iowa State College, to which the mammary gland be used as an index. In author will frequently refer, showed a the case of the rabbit, rat and mouse, marked mammary development and had pseudopregnancy normally extends for been lactating for a period of 3 or 4 weeks about one-half the normal period of preg­ before being presented for treatment. nancy. In these animals the complete Generally speaking, the dog has 2 breed­ growth of the mammary gland occurs, but ing seasons per year. Some of the smaller the gradual initiation of lactation which breeds may have 3°. The majority of normally develops during the second half females come into heat during March or of pregnancy does not appear. This con­ April, and again during September or Oc­ dition has been called "incomplete pseudo­ tober. Females first experience estrum pregnancy." In the marsupial (Dasyurus at the age of 5 or 6 months. The history viverrinus) , the ferret and the dog, pseudo­ of the Springer Spaniel discussed in this pregnancy extends for a period comparable article indicates that it either had a very to the normal pregnancy and the devel­ incomplete, transient first heat period that opment of the mammary gland includes went unnoticed, or that it did not come into the growth phase during the first half and heat until the eleventh month. the gradual initiation of lactation during The normal heat period begins with the the second half of the period. This condi­ onset of proestrum, which lasts for 7 to 9 tion is called "complete pseudopreg- days. The cycle continues insensibly into

32 The Veterinary Student the period of the estrum which also lasts After ovulation the corpus luteum de­ 7 to 9 days. Following this, there ensues velops, becomes solid at the end of estrum the period of metestrum. During this in­ or beginning metestrum and, as previously terval the corpus luteum is at maximum mentioned, remains fully developed for size and activity. By the thirtieth day after about 30 days when cellular degeneration the onset of metestrum, the corpus luteum begins. has begun to involute and at the ninetieth The uterine complexity continues to de­ day is completely involuted, at which time velop and remains so until about the anestrum sets in. The anestrual period twentieth day of metestrum when involun­ lasts about 2 months. tary changes set in. These continue until about the nineteenth day when the uterus Proestrum passes into the anestrus or quiescent stage. At the beginning of the proestrual pe­ During the zenith of their activity, the riod, the vulva shows an increasing amount epithelial cells of the uterine mucosa are of swelling and a clear sanguinary dis­ columnar, very much distended, have flat charge is seen at the ventral commissure basally located nuclei and show a very of the labiae vulvae. Throughout anes­ granular cytoplasm. The granules are trum the endometrium is shallow, the located principally in the portion of the epithelium low cuboidal with centrally lo­ cell facing the lumen. The gland lumina cated nuclei and the glands and crypts are small and contain a colloidal sub­ poorly developed. During proestrum and stance which stains pink to red with eosin. extending on into the first part of estrum, Metestrum there is not much change in the paren­ chyma, but in the interstitial tissue of the Towards the end of the metestrual pe­ endometrium there is a marked conges­ riod the cells become less tall, contain a tion and edema. The occurrence of some more spherical nucleus and are less gran­ capillary hemorrhage accounts for the ular. The lumina of the glands are larger presence of a sanguinous discharge at the and contain a considerable amount of col­ lips of the vulva. loid which stains as intensely as that seen At the end of the proestrum or begin­ during the middle of metestrum. Desqua­ ning estrum, the ovarian follicle ruptures mated epithelial cells may be found in the and the ovum is extruded. The ovum of lumina of the glands at this time. In ac­ the bitch is unique in that the first polar cordance with reports in the literature\ body has not been extruded at the time the author has noted that around the of ovulation. Consequently the egg is not forty-fifth day after the onset of metes­ mature and cannot be fertilized for a few trum, there is along with other retrogres­ days. sive changes, a breakdown of capillaries in the endometrium and a subsequent Estrum extravasation of blood into the interstitial By the sixth day of estrum the uterine tissue. No sanguinous discharge is usually glands have begun to show a marked ac­ seen at this time because the epithelium tivity. The epithelium is columnar, the of the uterine mucosa remains quite intact. crypts of the glands are well developed, Before discussing the histological and more coiled and extend deeper into the physiological changes occurring in the endometrium. The epithelial cells show uterus and ovaries during pseudopreg­ a marked granulation at this stage. The nancy, it would be well to review the his­ endometrium is becoming much deeper. tology of the corpus luteum. After the This activity seems to have been initiated rupture of the follicle and the discharge by the appearance of progesterone in the of the liquor folliculi and the ovum with blood circulation. Progesterone is secreted its corona radiata, the wall of the follicle by the cells of the stratum granulosum collapses. The epithelial membrana gran­ and theca interna of the corpus luteum, ulosa is thrown into folds and appears which begin their activity at the time of considerably thickened. The theca externa ovulation. keeps its regular circular outlines while

Summer, 1944 33 the theca interna, on the contrary, loses endothelium. These lutein cells seem to be them. At the base of the folds of the arranged in radial cords or strands. Be­ membrana granulosa the cells of the theca tween them networks of reticular fibers interna accumulate in triangular masses, can be demonstrated by the silver im­ while between the folds they are very pregnation method. S2arce or absent". Before going directly into a discussion of the anatomical, histological and physio­ Formation of the Corpus Luteum logical aspects of the typical pseudopreg­ The principal role in the formation of nant animal, it would be well to conclude the corpus luteum is played by the epi­ this discussion of the normal estral cycle thelial follicular cells. They begin at once in the dog by saying something about the to hypertrophy and in a few days attain hormones involved and their functions. a considerable size. Just when the forma­ When the female approaches the age of tion of progesterone begins is a matter puberty, the anterior lobe of the pituitary of speculation. Research workers report gland begins the production of significant the rise of the progesterone level in the amounts of follicular hormone (FSH) . blood stream previous to the time of ovu­ This causes the formation and develop­ lation. ment of ovarian follicles. Estrogens pro­ The lutein cell becomes polyhedral. The duced by the granulosa cells of a develop­ nucleus also swells and assumes a spheri­ ing follicle stimulate the development of cal form with a coarse chromatin network the accessory sex organs. As a result the and one or two nucleoli. Mitoses are rarely uterine endometrium and myometrium found, leading to the presumption that show a marked increase in size and ac­ the increase in size of the corpus luteum is tivity. In addition, these estrogens sensi­ due to cellular hypertrophy only. Such tize the tubular genital organs, making hypertrophied granulosa cells are called the action of the other hormones (pro­ lutein cells although the lipoid pigment gesterone, oxytocin) possible. Another "lutein" is at first found only in traces. The function of the follicular hormone is to large lipoid containing epithelioid cells initiate duct growth in the mammary of the theca interna remain scattered at gland. It does this by initiating the secre­ the periphery of the folded layer of lutein tion of mammogen I in the anterior lobe cells and accumulate in the folds. Their of the pituitary gland. inner structure is very similar to that of the lutein cells. They therefore have been Luteinizing Hormone given the name of "theca lutein cells" or The increase of estrogen secretion "paralutein cells" while the true lutein causes the luteinizing hormone (LH) to cells of epithelial origin are designated as be produced in the anterior lobe of the "follicular lutein cells." pituitary gland. This hormone is respon­ The true lutein cells have a clear, slightly sible for ovulation, preparing the uterus vacuolated cytoplasm which, though at for the implantation of the fertilized ovum first finely granular, shows a progressively and the maintenance of pregnancy for at greater accumulation of yellowish lipoid least part of its duration. A placental material. The theca-lutein cells have the hormone similar to progesterone assumes same structure but are smaller. Micro­ this function during the remainder of chemical examination reveals in the true the pregnancy period. In addition, pro­ lutein cells in this stage the presence of gesterone initiates the secretion of mam­ lipoids, chemically close to carotin, of the mogen II from the anterior lobe of the phosphatid and cerebroside types. In the pituitary gland. The latter hormone, called peripheral layers, especially in the theca­ the lobulo-alveolar factor, is responsible lutein cells, doubly refracting lipoids and for the formation and development of the cholesterol esters occur. terminal acini in the mammary gland. The polyhedral lutein cells are sur­ The progesterone level remains quite rounded by a network of large, sinusoidal high until just after parturition. Toward blood capillaries, the latter having a thin the end of pregnancy the estrogen level in-

34 The Veterinary Student creases in magnitude until it overrides during the heat period. About May 1, or the action of progesterone. Estrogen sensi­ approximately 60 days after ovulation and tizes the uterus so that oxytocin, a hormone conception would have taken place under produced in the posterior lobe of the pit­ ordinary circumstances, the animal began uitary, can initiate uterine muscular ac­ to lactate. The enlargement of the mam­ tivity and thereby bring about the ex­ mae took place slowly. When the case pulsion of the fetus. was presented at the clinic it had been Prolactin, secreted by the cells of the lactating for a period of 3 or 4 weeks. No anterior lobe of the pituitary gland, then other pertinent external manifestations initiates secretory activity in the mam­ were noticed and the disposition of the mary gland. Whether or not the increased animal was the same as it had been pre­ estrogen production is responsible for the viously. At the request of the owner an production of prolactin is a matter of oophorohysterectomy was performed. speculation. The ovaries and uterus were placed in 10 percent formalin fixing fluid for 24 hours and then stored for several days in 70 percent ethyl alcohol. The routine diox­ ane-paraffin method was used to dehy­ drate, clear, infiltrate and imbed the tis­ sues. A Weigert's-Heidenhain's-Van Gie­ son's picrofuchsin staining routine was fol­ lowed in preparing the sections for study. All sections were cut 6 microns thick. Histology From the histological studies made, it was determined that the stage of pseudo­ pregnancy had reached its zenith and that signs of beginning retrogression were evi­ dent. The endometrium of the uterus was beginning to show some signs of involu­ tion and a number of young ovarian fol­ licles contained well developed follicular cavities filled with liquor follicli. The uterine endometrium was as deep as that seen during metestrum and the coiled uter­ ine glands extended to the myometrium. Th ~ epithelial cells of the glands were columnar in the neck and body portions, but cuboidal at the bases of most glands. Top. Ovary from dog in metestrum. Increase It W 3 S here that involution was most no­ in size due to cellular hypertrophy of luteal cells. ticeable. The cuboidal cells and the col­ Bottom. Ovary from pseudopregnant bitch in which corpora lutea are much reduced in size. umnar cells in most instances contained a central nucleus. Very little granular mate­ Since the female Springer Spaniel rial could be seen in the cytoplasm. The spoken of previously in this discussion lumina of the glands were much larger presented such an exact duplication of a and contained a limited amount of colloidal typical case of pseudopregnancy, a de­ material and epithelial cell debris. This tailed histological study was made of her material stained rather lightly. uterus and ovaries. During the latter There was some hemorrhage seen in the part of February, 1944, the owner first superficial portions of the endometrium. noticed the dog in estrum. At that time It was very similar to that seen accom­ she was 11 months old. The bitch was panying the involutionary changes occur­ kept indoors so no copulation took place ring at the termination of the metestrum

Summer, 1944 35 Left. Endometrium of metestrum uterus. A. Portion of gland showing basally located nuclei and small acinus filled with secretory prcducts. Right. Endometrium of pseudopregnant uterus. B. Portion of gland showing centrally located nuclei and a large lumen. X 100. in the normal cycle. The musculature of monly accepted theory is that the follicle the myometrium was extremely well de­ stimulating hormone causes the growth veloped. The nuclei and cytoplasm of the and development of the young follicle. In outer longitudinal smooth muscle layer turn the estrogens secreted by it stimulate stained much more intensely than those the production of luteinizing hormone. of the inner circular layer. This luteinizing hormone causes the gran­ The ovaries were markedly smaller ulosa cells of the ovary to secrete proges­ than those taken from bitches in the terone, which in turn inhibits the forma­ metestrual stage of the sexual cycle. As tion of follicular stimulating hormone. previously mentioned, there were numer­ Thus the estrogen level is reduced. Since ous small follicles present, some of which estrogen stimulated the production of had follicular cavities. luteinizing hormone, the latter is produced in less amounts and the progesterone level Hormonal Relationship must necessarily fall. If pregnancy has One of the most controversial subjects ensued in the meantime, the progesterone­ in the dis~ussion of pseudopregnancy is the like hormone secreted by the placenta is hormonal relationships. Several theories sufficient to carry the fetus until parturi­ have been propounded concerning the an­ tion. The placental hormone does not tagonistic and synergistic action of the inhibit the formation of follicle stimulating follicle stimulating hormone (FSH) , the hormone (FSH) and consequently the luteinizing hormone (LH) , estrone and estrogen level is seen to rise towards the progesterone in the normal cycle. A com- end of pregnancy.

36 The Veterinary Student In pseudopregnancy as seen m the bitch, through the anterior pituitary to produce there is a disturbance in this hormonal re­ ovarian development and the formation of lationship. From histological studies made corpora lutea. Since the virgin bitch may of the ovaries of the pseudopregnant become pseudopregnant, it is evident that Springer Spaniel bitch, the progesterone the copulation stimulus is not needed to level was estimated as not being very initiate pseudopregnancy. It is not un­ high. Large vacuoles, presumably c:mtain­ reasonable to believe that the lack of a ing neutral fat, were found in practically nervous stimulation to the cells of the all of the lute:n cells. As contrasted to anterior pituitary producing follicular this, luteal cells examined in the corpora stimulating hormones is responsible for lutea of bitches in the metestrum period the failure of estrogen to override the

Left. Corpus luteum cells of metestrum ovary. A. Cell shows a few small vacuoles. Right. Corpus luteum cells of pseudopregnant ovary. B. Cells much vacuolated due to dissolving of neutral fat from cytoplasm by fat soluble fixatives. X 960. revealed the presence of small numbers effect of progesterone and terminate the of rather small vacuoles. At this time the luteal phase of the cycle. amount of progesterone secreted is very There are various methods of treating large. Nevertheless, without the presence the pseudopregnant condition of the bitch. of a considerable amount of progesterone These will vary according to the age of to act as an inhibitor (on the cells secret­ the animal, the amount of mammary en­ ing follicular stimulating hormone), the largement and the purpose for which the estrogen level was low. That it was low animal is kept. was concluded from the fact that the In a few instances where there is mam­ ovarian follicles were very immature. mary development to the point where the swelling becomes painful, symptomatic Theory of Cause treatment is sufficient. If the owner desires Cameronfi states that pseudopregnancy to use the animal fDr breeding purposes, in the rabbit is probably due to a nervous anterior pituitary hormone (FSH), one reflex set up through cDpulation acting of the naturally occurring estrogens, or

Sttmme'i', 1944 37 one of the synthetic estrogens such as percent of the cases presented with mam­ diethyl-stilbestrol can be used. There are mary tumors. Of the cases presented, 27 no clinical reports in the literature con­ percent were malignancies, 18 percent cerning the therapeutic value of these were mixed tumors, and 48 percent were products. Morphine has been used with adenofibromas (chronic cystic mastitis). some success. The nature of its action Often the mass lies within or near is uncertain. Where the owner keeps the the nipples and nodules are seen flaring up animal as a pet or servant, an oophoro­ coincident with the onset of estrum. Cyst­ hysterectomy can be performed. like formations begin to enlarge and appear as soft, blue areas beneath the skin. Many Relation to Tumors rupture and discharge a bloody fluid. Where the parenchyma is involved, a cys­ Although neoplastic enlargements in tic dilatation of the ducts of the teat and the mammae appear or increase in size occasionally of the lactiferous tubules is during proestrum, estrum and early met­ seen. A hyperplasia and papillomatosis of estrum, many cases of this kind occur at the duct epithelium commonly occurs. In a later stage in the cycle and often in con­ many instances mammary tumors are nection with pseudopregnancy. Likewise, sclerotic, resembling cartilage and bone. although mammary tumors are spoken of by many authors as being the result of an abnormally high estrin blood titre during Treatment the follicular phase of the sexual cycle, some have recognized neoplastic forma­ The best method of treatment, regard­ tions to be associated with an abnormally less of whether the condition is caused by high progesterone blood level. an estrogen or pregesterone blood level McCIelland7 states that whereas the disturbances, is oophorohysterectomy. If owner "thinks that the growth occurred the tumor is of a malignant nature, it after the pups were born," more often it should be removed immediately and the is noted several years after the last breed­ ovaries and uterus removed as soon as ing or in aging virgin bitches. Many times the animal is capable of undergoing an­ there is a history of an irregular estrual other operation. De Vitta reports that an cycle and lactation without pregnancy oophorectomy will prevent their occur­ (pseudopregnancy) . rence as well as recurrence, and that fol­ De VittaH states that non-pregnant lac­ lowing oophorohysterectomy benign tu­ tation is frequently noted following estrum mors regress in many instances without during one or more estrual cycles pre­ removal, provided they are not sclerotic. vious to the incidence in animals where neoplasms develop. REFERENCES Most mammary tumors are of a benign 1 Turner, C. W. and DeMoss. W. R. 1934. The no,'­ mal and experimental development of the nature, but many are malignant. In the mammary gland. Res. Bul. 207. Agr. Exp. Sla., literature many types of both, such as Co:lege of Agr., Univ. of Missouri. 2. Marshall, F. H. A. and Halman, E. T. 1916. On fibromas,fibrosarcomas,adenomas, adeno­ the post-oestrus changes occurring in the genera­ tive organs and mammarv glands of the non­ fibromas, adenocarcinomas, mixed tumors pregnant dog. Proc. Roy, Soc. of London. Series B. 89:546-558. chondromas and osteomas have been de­ 3. Dukes, H. H. The Physiology of the Domestic Animals. Coms:ock Pub. Co., Inc., Ithaca, N. Y. scribed. Adenofibromas, commonly re­ 1943. ferred to as chronic cystic mastitis, are 4. Keller, Karl. 1909. tiber den bau des endometri­ ums beim hunde mit besonderer berticksichti­ frequently associated with a hyperplasia gung der cyklischen veranderungen bei den uterindri.isen. Anatomische Hefte: Erste Ab­ of the endometrium and cystic ovaries. teilung; 39 Band; 117, 118, 119 Hefte. All of the above mentioned types have 5. Maximow, A. A. and B:oom, Wm. A Textbook of Histology. W. B. Saunders Co., Philadel­ been observed in connection with pseudo­ phia. 1941. 6. Cameron, A. T. Recent Advances in Endocrin­ pregnancy. ology. Blakiston Co., Philadelphia. 1940. Animals presented for treatment range 7. McClelland, Robert B. 1941. Tumors of the mam­ mary gland in dogs. No. Am. Vet. 22 (8) :491- from 8 to 14 years of age. Boston Terriers, 493. 8. DeVitta, Joseph. 1939. Mammary adenofibroma of according to one reportS comprised 43 the female dog. No. Am. Vet. 19 (3) :53-55.

38 The Veterinary Student