The Uterus: Normal Postpartum Involution

Chapter 9

The Uterus: Normal Postpartum Involution

Cow Ewe Doe (Goat) Sow

Bitch Placental Sites Interplacental Site Endometrium Queen Placental Sites Interplacental Site Endometrium

Mare

Bibliography

T o recognize and evaluate pathologic alterations in the postpartum uterus, it is first essential to know the gross and microscopic changes that occur during nor­ mal involution. Uterine involution in domestic mam­ mals has been investigated in all species but most ex­ tensively in the cow and the e w e . Most studies have been concerned with the time o f return o f the uterus to its approximate pregravid size, but the uterus is not prepared for the maintenance o f normal preg­ nancy at this stage. Additional time is required for the establishment o f the normal physiologic functions necessary for conception and maintenance o f preg­ nancy. Involution occurs most rapidly in the mare and sow and least rapidly in the bitch.

clinical examinations and plasma progesterone assays o f dairy cows during 183 postpartum periods. T h e y stated that "the present data indicate the duration o f the post partum p e r i o d to be 40—50 days. A f t e r this period uterine involution is completed and the cow has regular cyclic ovarian activity." I have examined the reproductive organs from 15 Holstein-Friesian heifers that had calved for the first time. A l l had delivered normal calves and appeared to be disease free. T h e y w e r e slaughtered from 2 through 30 days postpartum. T h e uteri w e r e cul­ tured for bacteria and fungi. T h e ovaries and uterine tubes w e r e separated f r o m the rest o f the reproduc­ tive tract and the broad ligaments w e r e r e m o v e d ad­ jacent to the junction with the uterine horns. T h e uterine content was r e m o v e d and measured. T h e uterine horns w e r e separated from the cervix and each horn was measured and weighed. Tissue sec­ tions w e r e prepared from the cranial, middle, and caudal portions o f each horn. T h e weights o f the uterine horns, characteristics o f the lochia, and cul­ ture results are presented in T a b l e 9.1. T h e uterus, minus the cervix, w e i g h e d 7175 g in o n e cow at Day 2 postpartum and 3567 g in another cow at Day 4. T h e average uterine weight was 793 g at Days 12 to 15 and 509 g at Day 30. T h e previously gravid horn w e i g h e d about 100 g m o r e than the nongravid horn at Day 30, which is in agreement with the report by W a g n e r and Hansel (1969).

Cow M o r r o w et al. (1969a), Garcia (1982), and Leslie (1983) reviewed the literature on postpartum involu­ tion o f the bovine uterus. Garcia stated that "the post­ partum period in the cow starts with parturition and lasts until uterine involution is completed and the ani­ mal has resumed regular oestrous cycles with normal oestrous behavior." T h e interval from parturition to complete uterine involution is significantly l o n g e r in pluriparous than in primiparous cows (Buch et al., 1955; M o r r o w et al., 1966). Marion et al. (1968) r e p o r t e d that the "average intervals from parturition to complete involution f o r primiparous and pluriparous cows w e r e 34.0 and 40.6 days, respectively, a highly significant (p < 0.01) difference." Garcia and Larsson (1982) conducted

Gier and M a r i o n (1968) examined the reproduc­ tive tracts from 57 clinically normal cows at Day 1 through Day 60 following parturition. Each uterus was t r i m m e d o f excessive fat and separated from the

125

126

9. The Uterus: Normal Postpartum Involution

Table 9.1 Postpartum Uterine Involution in the C o w Uterine Weight (g)

Accession Number

Gravid

Nongravid

Total

Cervical Weight

2

9295

5050

2215

7265

600

710 ml, thin, bright red fluid

4 9

9245 9410

3180 1121

387 483

3567 1604

647 534

10

9227

944

391

1335

303

12

9216

523

270

793

272

165 ml, dark red fluid 1000 ml, thick, brown-red fluid with tan particles 500 ml, dark red-brown, mucoid material 25 ml, thick brown fluid with sandlike particles

13 15 16 17 22 30

6760 9194 6768 6769 6702 7358

554 539 424 337 245 316

204 290 246 161 176 211

758 829 670 498 421 527

292 238 256 224 267 145

30 30 30 30

7410 7556 7610 7615

253 346 345 298

164 208 223 180

417 554 568 478

217 180 140 143

Day

Uterine Content

a

Small amount of clear mucus

— — —

Small amount of clear thin mucus N o content N o content N o content N o content

Culture Results E. coli C. perfringens Sterile 5. bovis Sterile E. coli Sterile Sterile Sterile Sterile Sterile Sterile Sterile Sterile Sterile Sterile

"Not recorded.

vagina by cutting the tract 20 m m caudal to the exter­ nal os. T h e uterus was weighed, measured, and pho­ tographed. Placental remnants and uterine fluids, if any, were r e m o v e d and weighed. T h e y reported that " T h e weight o f the average uterus decreased from 9.0 kg at parturition to 1.0 kg at 30 days and to 0.75 kg at 50 days." T h e weight o f uterine fluid ranged from 800 to 2000 g from Day 1 through Day 8 post­ partum with the largest amount on Day 6. T h e uteri contained 125 to 750 g o f fluid from Days 10 through 16. T h e volume o f uterine content in my cases varied from 165 to 1000 ml during the first 9 days postpar­ tum. V e r y little fluid was present after Day 12. T h e color o f the uterine fluid changed f r o m bright red to dark brown as the interval from parturition to slaughter increased. T a n particles o f necrotic caruncular tissue were present in the fluid during Days 6 and 9. Rasbech (1950) conducted clinical examinations o f postpartum heifers and cows. H e reported that " A few primiparae discharge almost n o lochia, but ab­ sorb practically the entire uterine contents. O l d e r multiparae discharge from 800 to 2,000 ml lochia." T h e average lochial discharge in heifers was 500 ml. Elliott et al. (1968) cultured uteri for bacteria from 106 postpartum cows. Luminal washings and e n d o ­ metrial tissue w e r e inoculated into six different me­ dia and incubated at 37°C under atmospheric condi­ tions, increased carbon dioxide, and strict anaerobic conditions. "Bacterial recoveries w e r e made from 93

percent o f the uteri from cows three to 15 days, 78 percent o f those between 16 and 30 days, 50 percent between 31 and 45 days and only nine percent o f those between 45 and 60 days." Thirty-three differ­ ent species o f bacteria w e r e isolated f r o m 66 to 106 uteri: "Staphylococcus epidermidis was isolated from 15 uteri; Pseudomonas sp., 12 times; Corynebacterium bovis seven times; and Streptococcus faecalis and Micrococcus sp. four times each. . . . Thirty-six recoveries were made from tissue inoculum only, two were recovered from luminal flushings only and 28 from both tissue and flushings." It appears to be necessary to use tis­ sue inoculum as well as uterine content for determin­ ing uterine infections in postpartum cows. Rasbech (1950) reported that "Infection with Cory­ nebacterium pyogenes in pure culture in puerperal cows is the most frequent (28.3 percent). T h i s infection is accompanied by considerable macroscopic changes in the lochial discharge, which becomes m o r e purulent towards the end o f the involution period, being whit­ ish o r yellowish white." Pure cultures o f Escherichia coli w e r e found in 26.7%, pure cultures o f staphylo­ cocci in 16.7%, and mixed bacterial infections in 25% o f the cows. I n the postpartum heifers which I examined, E. coli, Streptococcus bovis, and Clostridium perfringens w e r e isolated f r o m the uteri o f animals slaughtered o n Days 2, 9, and 12 postpartum. T h e uteri w e r e bacteriologically sterile in heifers slaughtered on Days 4, 10, and 13 through 30. A c c o r d i n g to A r t h u r (1975), "the negative pressure which is present in the genital tract

Cow

immediately after expulsion of a fetus induces an in­ rush of air and this often causes contamination and later colonization of the uterus by organisms which normally populate the vestibule of the particular spe­ cies." Bretzlaff and Ott (1983) determined the preva­ lence of uterine infection in pastured beef cows dur­ ing the first 2 weeks after calving. They sampled "uterine contents using modified Teigland swabs with a double-glove technique." The prevalence of positive cultures was 9 of 26 (35%), which "was less than reported for normally calving postpartum dairy cows subjected to the same method of uterine sam­ pling." Nine of 12 samples (75%) collected from dairy cows within 5 days of calving yielded bacterial iso­ lates. These cows calved in continuously occupied maternity stalls that were undoubtedly contaminated. The gross changes in the normal postpartum bo­ vine uterus are most prominent in the caruncles. The caruncular tissue above the vascular stalk undergoes necrosis and fragmentation and is sloughed into the uterine lumen. By Day 2 postpartum, irregular, wedge-shaped, red areas are present in the luminal half of the caruncle. By Day 4, the caruncles are dark red and soft. The dark discoloration extends to the vascular stalk, which is white. By Days 9 to 12, all the necrotic caruncular material has sloughed from the surface of the stalk leaving a granular surface with a few small hemorrhagic foci. It continues to have a granular, nonglistening surface until it is covered by the in-growth of adjacent surface epithelium. The surface epithelium in the intercaruncular areas of the endometrium remains intact throughout the postpar­ tum period, giving the surface of the intercaruncular tissue a glistening appearance. If the epithelium is de­ nuded as a result of endometritis, the surface appears granular and nonglistening. The endometrium is light to dark brown from the presence of hemosiderin-laden macrophages. The surface of the caruncles begins to glisten by Day 15 because of the regenera­ tion of the surface epithelium. By Day 30, the carun­ cles appear to be normal on gross examination. The endometrium is still brown because of the presence of hemosiderin. The sequential histologic changes during postpar­ tum involution of the bovine uterus have been re­ ported by Rasbech (1950), Gier and Marion (1968), Wagner and Hansel (1969), and Archbald et al. (1972). The following description of the histologic changes are based on material that I have examined. All the specimens were from clinically normal heifers. Fifteen previously mentioned specimens were ob­ tained following slaughter and three were collected by incising a portion of the uterine wall through a flank incision. The latter specimens were provided by Dr. Katherine Bretzlaff of the University of Illinois.

127

The histologic descriptions are based on examination of the previously gravid uterine horn.

Day 2—Postmortem Specimen (Acc. No. 9295) Hemorrhagic infarcts (Fig. 9.1), associated with de­ generative and proliferative vascular lesions, were present in many of the caruncles on Day 2 postpar­ tum. The lesions occurred in arteries as they passed through the thick zone of collagenous connective tis­ sue on the superficial part of the vascular stalk of the caruncle. Early vascular lesions consisted of hydropic degeneration of the cells in the intima and adjacent media. Some of the nuclei of affected cells were en­ larged and others pyknotic. Intimai proliferation of loosely arranged spindle-shaped cells with abundant, pale blue cytoplasm narrowed the arterial lumen and apparently caused blockage of the vessels in the fi­ brous tissue septa of the caruncle. Multifocal colonies of large, gram-negative rods were present in the in­ farcts. Escherichia coli and C. perfringens were isolated

from the uterus. Most of the crypts in noninfarcted areas of the caruncle were filled with necrotic epithe-

Fig. 9.1. Intact and incised caruncles from a cow 2 days postpartum. The wedge-shaped dark areas in the cut speci­ men are foci of infarction. Acc. N o . 9295.

128

9. The Uterus: Normal Postpartum Involution

liai cells. Viable maternal epithelium was present in only a few areas. The depths of a few crypts con­ tained viable trophoblastic cells and fetal placental mesenchyme. The surface epithelium was intact throughout the uterus. It consisted of pseudostratified columnar cells, some of which contained basal vacuoles. The zona compacta was thick and contained numerous eo­ sinophils and a few neutrophils. Dense focal accumu­ lations of these cells were present below the surface epithelium and many were migrating through the ep­ ithelium. The zona spongiosa was edematous and contained widely dilated lymphatics. The endometrial glands were dilated, lined by low columnar epithelium, and surrounded by a zone of collagenous connective tis­ sue. Numerous large, spherical cells with abundant, coarsely granular, blue-gray, cytoplasmic bodies, were located in the basal portion of the epithelium. The nuclei of normal-appearing cells were adjacent to the lumen. Archbald et al. (1972) reported that these de­ generative changes occur in the glandular uterine ep­ ithelium of the prepartum cow. D a y 4 — P o s t m o r t e m S p e c i m e n ( A c c . N o . 9245)

Infarction of the caruncles involved most of the tissue above the vascular stalk (Fig. 9.2). The connective tis­ sue septa were spared and had an increased amount of collagen fibers. The vascular lesions in the stalk were more advanced than at Day 2. In addition to the arterial lesions, there was degeneration of veins in and below the zone of dense fibrous tissue. Wavy bands of hyaline material were present in the venous walls, and loosely arranged fibrous tissue had prolif­ erated adjacent to the endothelium. The walls of the

Fig. 9.2. Intact and incised caruncles from a cow 4 days postpartum. All the caruncular material is necrotic down to the stalk. Acc. N o . 9245.

veins were not uniformly involved. Neutrophils, eo­ sinophils, macrophages, and a few multinucleated gi­ ant cells were present in the periphery of the necrotic tissue and in the zone offibroblasts.Small mononu­ clear cells were evenly dispersed among the fibro­ blasts, and there was neoformation of small blood vessels. A few small islands of viable chorionic tissue were present in some caruncles. Bacteria were not isolated from the uterus nor were bacteria found in the infarcted tissue. The surface epithelium in intercaruncular areas was intact and consisted of cuboidal to columnar cells that were not pseudostratified as at Day 2. Some of the epithelial cells had basal vacuoles containing hya­ line droplets. Collagen fibers were increased in the zona compacta, which contained a few small lymph­ ocytic foci. The collagenfiberssurrounded blood ves­ sels and were dispensed throughout the zona com­ pacta. Polymorphonuclear leukocytes were not evident. Less edema of the zona spongiosa was present than on Day 2 and the lymphatics were partially collapsed. The endometrial glands were moderately dilated and surrounded by prominent collagen fibers. The glan­ dular epithelium was low columnar and contained a few mitotic figures. Large cells with coarse, bluebrown, cytoplasmic granules were present in the basal part of the epithelium. Macrophages with similar pig­ ment were present in the lumina of endometrial glands and in the connective tissue surrounding some of the glands. D a y 5 — B i o p s y S p e c i m e n ( A c c . N o . 19611)

Numerous interstitial cells with foamy cytoplasm (foam cells) and multinucleated giant cells sur­ rounded dark blue cellular debris in the caruncles. The small arteries in the collagenous zone of the stalk had thick muscular walls and very small lumina. The mesenchymal tissue had proliferated and resembled the normal stroma of the nongravid caruncle. This proliferation occurred beneath the dense connective tissue zone of the caruncle and appeared to be an early stage of regeneration. A portion of fetal pla­ centa was present on the edge of some caruncles. Pyknosis and karyorrhexis of the chorionic mesen­ chyme had occurred, but the trophoblastic cells were viable. Cuboidal to columnar epithelium covered all the intercaruncular endometrium. Large apical vacuoles were present in many of the epithelial cells. Abun­ dant collagen was present in the zona compacta. Most of the endometrial glands had small lumina and were lined by low columnar epithelial cells with relatively little cytoplasm. The epithelial cells were taller in the glands near the zona compacta. The lymphatics were

Cow

129

not prominent and abundant collagen was present in the depth of the endometrium. Relatively few inflam­ matory cells were evident in the endometrium.

pigmented macrophages were present in the connec­ tive tissue surrounding the glands. Neutrophils and eosinophils surrounded occasional glands.

Day 7—Biopsy Specimens (Acc, Nos. 19613 and 19661)

Day 10—Postmortem Specimen (Acc. No. 9227)

Granulation tissue with small islands of necrotic ma­ terial covered the caruncular stalk. Large areas of hemorrhage surrounded the areas of necrosis. Many of the mesenchymal cells had heavily vacuolated cyto­ plasm. There was pyknosis and karyorrhexis of the cells in the intima and media of arteries and thrombo­ sis of veins. The amount of collagenous connective tissue covering the caruncular stalk was reduced, and it had disappeared adjacent to large blood vessels. Nonorganized thrombi were present in veins in the caruncular stalk. Epithelium covered most of the stalk. The intercaruncular tissue was covered by colum­ nar epithelium. A few neutrophils were present in the zona compacta and in the surface epithelium. Less collagen was present in the zona compacta than on Days 4 and 5. Most of the glands in the depth of the endometrium had small lumina containing a few macrophages and were lined by low columnar epithe­ lium containing a few pyknotic cells. Some of the basal glands were lined by flattened to columnar epi­ thelium and were surrounded by abundant collage­ nous connective tissue. A few glands contained brightly eosinophilic, granular material and pyknotic nuclei.

Bacterial cultures of the uterus were sterile. Epithe­ lium had not regrown over caruncles in the pre­ viously gravid uterine horn (Fig. 9.3). The histology of the uterus was similar to the uterus on Day 9, with the exception that there were no pockets of exudate in the caruncles. Lymphocytic foci were present in the intercaruncular endometrium.

Day 12—Postmortem Specimen (Acc. No. 9216) Escherichia coli was isolated from the uterus following slaughter. Only a small amount of lochia was present in the uterine lumen (Fig. 9.4). Epithelium was grow­ ing in from the sides of the caruncle, but the major

Day 9—Postmortem Specimen (Acc. No. 9410) The caruncular stalks were short and broad. Surface epithelium extended for a short distance up the edge of the caruncles. The major portion of the caruncular surface was covered by granulation tissue and exu­ date. A few large areas of hemorrhage were present in the superficial part of some of the caruncles. In a few areas, the intima of arteries contained abundant, loosely arranged fibrous tissue. Columnar epithelium covered the intercaruncular endometrium. Small, multifocal lymphocytic foci and a few neutrophils and eosinophils were present in the stratum compactum. A pure culture of Strep, bovis was isolated from the uterus. Moderate-sized islands of collagen fibers were dispersed throughout the stra­ tum compactum. The endometrium was comparatively narrow and collagen fibers were abundant, especially in the basal area. The glands were lined by columnar epithelium. A few necrotic cells and macrophages were present in the lumina. Cells with pigment-containing cytoplasm were present in the basal part of the epithelium, and

Fig. 9.3. Ten-day postpartum bovine uterus with de­ nuded epithelium in the caruncles of the right uterine horn. Acc. N o . 9227.

130

9. The Uterus: Normal Postpartum Involution

ment granules stroma.

were located in the

surrounding

D a y 1 3 — P o s t m o r t e m S p e c i m e n ( A c c . N o . 6760) T h e caruncles were partially covered by epithelium. Prominent lymphocytic foci were present in the caruncular stroma, and there were a few small lymph­ ocytic foci in the stratum compactum o f the intercar­ uncular endometrium. N o bacteria were recovered from the uterus.

D a y s 15, 16, a n d 1 7 — P o s t m o r t e m S p e c i m e n s ( A c c . N o s . 9194, 6768, a n d 6769) A small amount o f clear mucus was present in the uterine lumen on Day 15 and the surface o f the carun­ cles was beginning to glisten (Fig. 9.5). Bacteria were not isolated from the uteri on Days 15, 16, and 17. T h e edges o f the caruncles were covered by epithe­ lium, but the central portions were denuded. L a r g e lymphocytic foci were present in the superficial caruncular stroma. Many o f the arteries in the caruncular stalks had light blue, lacy, intimai fibrous tissue. T h e amount o f collagen in the intercaruncular enFig. 9.4. Twelve-day postpartum bovine uterus with small amount of lochia in the uterine lumen. Acc. N o . 9216.

portion o f the caruncular surface was d e n u d e d . Less granulation tissue was present than on Day 9, and there was a marked proliferation o f normal-appear­ ing caruncular stroma. A few necrotic blood vessels protruded through the surface o f the caruncles. O r ­ ganizing thrombi were present in some o f the vessels in the stalk. L a r g e lymphocytic foci were present in the stroma. T h e epithelium covering the intercaruncular en­ dometrium was low to tall columnar. L a r g e , oval to spherical basal cells with pale brown cytoplasmic granules were present in the epithelium. Many neu­ trophils and lymphocytes were migrating through the surface epithelium. L a r g e perivascular lymphocytic foci were present in the stratum compactum. A few endometrial glands adjacent to caruncles were widely dilated, lined by cuboidal to flattened ep­ ithelium, and surrounded by a wide zone o f collagen fibers. It appeared that these glands w e r e obstructed during involution o f the caruncles. T h e rest o f the endometrial glands had small lumina and were lined by columnar epithelial cells. P i g m e n t e d cells were present in the basal portion o f the epithelium and macrophages containing dark brown cytoplasmic pig-

Fig. 9.5. Fifteen-day postpartum bovine uterus that is de­ void of lochia. Acc. N o . 9194.

Ewe

dometrium had decreased. S o m e o f the glands adja­ cent to caruncles w e r e dilated and surrounded by a wide zone o f collagen fibers. Perivascular and peri­ glandular accumulations o f lymphocytes and eosino­ phils w e r e present in a few areas o f the stratum spongiosa. T h e stratum compactum was relatively free o f inflammatory cells.

131

infection in cattle. Probably culture data are not reli­ able unless the uterine samples are collected by lapa­ rotomy o r at a careful necropsy to avoid contamina­ tion. Organisms from the vagina are frequently drawn into the uterus during slaughter, especially when the cervical canal is o p e n .

Ewe D a y 2 2 — P o s t m o r t e m S p e c i m e n ( A c c . N o . 6702) Some o f the caruncles w e r e c o v e r e d by epithelium, but others had d e n u d e d centers. Prominent lymph­ ocytic foci w e r e present in the caruncles and in the zona compacta o f the intercaruncular tissue. A large amount o f pale blue, lacy, fibrous tissue was present in the intima o f the caruncular arteries. T h i s lesion extended along the vessels into the m y o m e t r i u m . Cystic glands with flattened epithelium and periglan­ dular fibrosis w e r e present adjacent to and underly­ ing some o f the caruncles.

Day 30—Postmortem Specimens ( A c c . N o s . 7358, 7410, 7556, 7610, a n d 7615) T h e s e cases w e r e selected at r a n d o m from a large se­ ries o f clinically normal heifers slaughtered 30 days after parturition. T h e uteri w e r e bacteriologically sterile in all cases. A l l the caruncles w e r e covered by columnar epi­ thelium. T h e vascular lesions w e r e similar to those present in the Day 22 uterus. N u m e r o u s macro­ phages with pale brown, cytoplasmic pigment gran­ ules were present in the caruncular stroma and in the zona compacta o f the intercaruncular e n d o m e t r i u m . Lymphocytic foci w e r e present in the caruncular stroma and in the stratum compactum in three o f the five heifers. M o r e investigations need to be conducted o n the m o r p h o l o g y and microbiology o f the postpartum uterus o f the cow. T h e literature reports concerning the histology o f the postpartum bovine uterus are rather sketchy. I have described the histologic changes in the e n d o m e t r i u m in a limited number o f bovine uteri at Days 2 through 30 postpartum. T h e infected uteri o f heifers slaughtered o n Days 2 through 12 revealed histologic differences from those that w e r e bacteriologically sterile. T h e infected uteri had colonies o f bacteria in necrotic caruncular tissue, dense neutrophilic infiltrates, and large peri­ vascular lymphocytic foci in the glandular portion o f the endometrium. T h e popular belief that all post­ partum bovine uteri b e c o m e infected appears to be incorrect. I believe that most o f the bacterial incidence data greatly overstate the problem o f postpartum uterine

Involution o f the ovine uterus has been described by U r e n (1935) and van W y c k et al. (1972a,b). U r e n con­ cluded that uterine involution was complete at 30 days postpartum. I n their first article, van W y c k et al. stated that uterine involution was complete by Day 30. I n their second article, they reported that "from a macroscopic point o f view, then, the uterus appears to have completed involution by the 20th to the 24th day postpartum. . . . O n the other hand, as shown his­ tologically, the caruncles are covered with epithelium only by the 28th day." Call et al. (1976) concluded that uterine involution "was generally complete by Day 24." Foote and Call (1969) r e p o r t e d that the total uter­ ine weights for "lactating ewes w e r e 1,256, 1,088, 261, 106 and 96 g m for Day 0, 3, 10, 17 and 24, re­ spectively." T h e y did not mention h o w the uteri w e r e trimmed. N o n e o f the cited references mentioned bactériologie examination o f the postpartum ovine uterus. I have examined the reproductive tracts from 30 ewes that w e r e slaughtered at intervals from 2 hours through 49 days following parturition. T h e uteri w e r e cultured f o r bacteria and fungi and trimmed ac­ cording to the procedure described for the bovine re­ productive tract. T h e uterine and cervical weights and the character o f the uterine content o f 17 twoyear-old ewes are presented in T a b l e 9.2. Bacteria and fungi w e r e not isolated from any o f the uteri. T h e weights o f the uterine horns ranged from 609 to 1035 g during the first 3 days postpartum. T h e average uterine weights at 7, 14, 21, 28, 35, and 42 days w e r e 258.8, 219.5, 82.5. 30.5, 28.5, and 20.5 g, respectively. T h e placenta was usually expelled within 2 to 4 hours following parturition. I n contrast to the cow, very little fluid was present in the postpartum ovine uterus. A small amount o f bright red blood was pres­ ent in the uterine lumen during the first 8 to 10 hours, and this turned dark b r o w n by 12 hours. Some o f the caruncles w e r e flat and others cup-shaped dur­ ing the first 12 hours. It appeared that the separation o f the fetal placenta caused eversion o f some o f the cup-shaped caruncles. A t 12 hours and Day 3 postpartum, the caruncles w e r e cup-shaped (Fig. 9.6) and pale grey, and w e d g e -

132

9. The Uterus: Normal Postpartum Involution

Table 9.2 Postpartum Uterine Involution in the Ewe Uterine Weight (g)

Day

Accession Number

Number of Lambs

L. Horn

R. Horn

1/2

8666

1

354

256

610

62

3

8644

1

202

407

609

67

3

8682

2

523

512

1035

56

3

8683

1

250

480

730

48

7

8635

1

115

230

345

30

7

8637

1

44

127

171

18.5

14

8636

1

110

181

291

34

14

8694

1

59

89

148

29

21

8673

1

20

42

62

10

22 28 28 35 35 42 42 49

8701 8672 8780 8793 8798 8839 8878 8833

2 1 1 1 2 1 1 1

49 12 14 12 14 12 9 10

54 14 21 16 15 10 10 10

103 26 35 28 29 22 19 20

29 10 12.5 10 9.5 12 10 11.5

shaped areas o f h e m o r r h a g e extended into some o f the decidual caruncular tissue. By Day 7 and continuing through Day 21, the ne­ crotic portions o f the caruncles were dull red, flat­ tened, and covered by dark brown, tenacious material (Fig. 9.7). T h e necrotic tissue could be r e m o v e d easily on Days 14 and 21. T h e vascular stalks o f the carun­ cles were edematous on Day 7. T h e uterus was empty, except for a small amount o f clear mucus in all ewes slaughtered between Days 28 and 49. Many o f the ewes had focal brown areas in the endometrium, especially near the uterine body. T h i s discoloration was due to blood pigment from hemorrhage secondary to trauma sustained during parturition. Irregular-shaped, linear white areas were present in the intercaruncular tissue in some o f the ewes slaughtered between Days 28 and 42. Pro­ gressive reduction in the size o f the uterus occurred up to Day 42. It appears from these observations that the ovine uterus is not completely involuted by Days 24 to 30 as reported in the literature. Most o f the re­

Total

Cervical Weight

Uterine Content Small amount of dark brown, tenacious material around cupped caruncles Small amount of dark brown, thick material around cupped caruncles Small amount of dark brown, thick material around cupped caruncles Small amount of dark brown, thick material around cupped caruncles Caruncles necrotic and flattened; small amount of thick, dark brown material around caruncles Caruncles necrotic and flattened; small amount of thick, dark brown material around caruncles Similar to Day 7, but necrotic caruncular tissue can be removed easily Similar to Day 7, but necrotic caruncular tissue can be removed easily Similar to Day 7, but necrotic caruncular tissue can be removed easily Moist, tan-brown necrotic caruncles N o content Small amount of clear mucus Small amount of clear mucus N o content N o content N o content Small amount of clear mucus

ported studies have not extended beyond Day 30 postpartum.

D a y 1 — T w e l v e E w e s W e r e S l a u g h t e r e d o n the Following H o u r s Postpartum: 2 (Acc. N o s . 7922, 7925, a n d 7931), 5 ( 7 9 1 6 ) , 6 (7914 a n d 7926), 10 ( 7 9 1 5 ) , 12 (7911 a n d 8666), 15 ( 7 9 1 3 ) , 17 ( 7 9 2 8 ) , a n d 18 (7927) T h e surface o f the caruncles was covered by blood from hematomas that had ruptured during expulsion o f the fetal membranes. Hematomas are a normal feature o f the placentome o f sheep. Maternal blood is extravasated between the chorionic villi and the apical segments o f the intercryptal septa o f the carun­ cle (Wimsatt, 1950). T h e crypts were lined by mater­ nal syncytium with numerous clusters o f tightly packed nuclei. A few binucleate trophoblast cells and cellular debris w e r e present between the septa. A zone o f hyaline connective tissue was present at the base o f the septa.

Ewe

133

van W y c k et al (1972a) stated that " A histological study o f the placentome o f the e w e before and during parturition revealed that shortly before parturition the connective tissue o f the proximal areas o f the ma­ ternal villi and adjacent caruncular tissue becomes hyalinized.' U r e n (1935) reported that at approxi­ mately 12 hours after parturition "all o f the blood vessels in the area o f hyaline degeneration on the in­ ner side o f the placental matrix band, and in the crypt mass, are thrombosed." T h r o m b i w e r e not seen in the uterine caruncles that I e x a m i n e d during the first 18 hours postpar­ tum. T h e r e was vacuolation o f the cytoplasm and pyknosis and karyorrhexis o f many cells in the media o f the thick-walled arterioles in the caruncula septa. Reduction o f blood flow to the caruncles in the early postpartum p e r i o d may be due to the constriction o f arterioles supplying the caruncles. Makowski (1968) r e p o r t e d that the radial arterioles o f the caruncle have a thick muscular wall and that similar aterioles are not found elsewhere in the uterus. A localized area o f constriction o f the arterioles is present along the base and periphery o f the caruncle before pene­ trating the septal area. T h e arterioles are dilated be­ y o n d the area o f localized constriction. H e suggested that the constrictions o f the arterioles probably serve as sphincters that regulate maternal blood flow through the caruncle. T h e surface epithelium was intact in the intercar­ uncular area and on the e d g e o f the caruncles up to the area o f the previous junction between the chori­ onic villi and the caruncular septa. D e n u d e d epithe­ lium was not seen at any time during the process o f uterine involution. T h e surface epithelium and the underlying zona compacta w e r e arranged in coarse folds that became m o r e prominent at 6 hours post­ partum. T h e surface o f the endometrium and the uterine glands w e r e lined by tall, columnar epithe­ lium. N u m e r o u s degenerating cells w e r e present in the basal portion o f the glandular epithelium. T h e uter­ ine glands w e r e widely dilated at 2 hours and became somewhat collapsed as the interval from parturition to slaughter increased. Neutrophils w e r e present in the uterine glands in 4 o f the 12 uteri. ,

Fig. 9.6. Twelve-hour postpartum ovine uterus with small amount of blood in the uterine lumen, cervix, and vagina. Acc. N o . 8666.

D a y 2 ( A c c - N o s . 7920 a n d 7921)

Fig. 9.7. Seven-day postpartum ovine uterus with dark brown tenacious material in the uterine lumen and cervix. Acc. N o . 8635.

T h e superficial portions o f caruncular septa w e r e ne­ crotic. M a n y o f the nuclei o f the maternal syncytium w e r e pyknotic, and cellular debris was present be­ tween the septa. Fresh thrombi w e r e present in the septal arterioles and numerous red blood cells were present in the spaces between the septa. A few foci o f mineralization w e r e present in the hyaline zone.

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9. The Uterus: Normal Postpartum Involution

T h e surface epithelium and the compact zone were markedly folded. T h e uterus o f e w e 7920 had numerous neutrophils in the glandular lumen and a scattering o f neutrophils in the surrounding stroma. Numerous degenerate cells w e r e present in the basal portions o f the glands. Ewe 7921 had a very mild neutrophilic reaction and a few degenerate cells in the glandular epithelium. A moderate number o f lymphocytes w e r e present in the glandular epithe­ lium and in the surrounding connective tissue.

D a y 3 ( A c c . N o s . 8682, 8683, a n d 8686) T h e distal one-fourth to one-third o f the caruncular septa were necrotic. H e m o r r h a g i c infarcts extended into the septal mass as far as the hyaline zone o f con­ nective tissue. T h r o m b i w e r e present in arterioles in the hyaline zone adjacent to the infarcts. T h e d e g e n ­ erative arteriolar lesions w e r e similar to but m o r e ad­ vanced than those seen on Day 2. A few arterioles had fibrinoid necrosis. A few areas o f mineralization w e r e present in the hyaline zone. Most o f the maternal epi­ thelial syncytium was degenerate with numerous ar­ eas o f detachment o f necrotic tissue. T h e surface epithelium and associated compact zone were folded into the uterine lumen. T h e zona compacta was narrow and contained macrophages and a few lymphocytes. Dense hyaline material sur­ rounded the capillaries. T h e lumina o f the endometrial glands w e r e smaller than on Day 2. Abundant cellular debris and neutrophils w e r e present in the glandular lumina. Vacuoles containing cellular debris w e r e present in the basal portions o f the epithelium, and a few neu­ trophils w e r e presentin the surrounding stroma.

tained cellular debris. N u m e r o u s lymphocytes w e r e present in the basal portion o f the glandular epithe­ lium and a scattering o f lymphocytes, and a few neu­ trophils and plasma cells, w e r e present in the intersti­ tial tissue. T h e tunica propria had marked edema.

D a y 8 ( A c c . N o s . 8630 a n d 8671) T h e septal mass o f the caruncles d o w n to the hyaline basal zone, which had irregularly shaped areas o f mineralization, was necrotic. T h e r e was m o r e exten­ sive regeneration o f connective tissue underlying the hyaline zone and m o r e advanced regeneration o f epi­ thelium covering the basal portions o f the septa than on Day 7. T h e arterioles and arteries in the vascular stalk o f the caruncles had a pronounced increase o f loosely arranged, pale blue-staining material in the intima. T h e intercaruncular endometrium was similar to that seen o n Day 7. P i g m e n t e d macrophages w e r e present through the tunica propria.

D a y 14 ( A c c . N o s . 8636 a n d 8694) T h e appearance o f the caruncles was similar to that seen o n Days 7 and 8 with the major exception that the edema in the vascular stalks had subsided consid­ erably. T h e lymphatics in these areas w e r e still very prominent. T h e tips o f the low, wavy folds o f the surface epi­ thelium had papillary proliferations. A few plasma cells and macrophages w e r e present in the zona com­ pacta. Less collagen was present in the zona compacta than on Day 7. T h e endometrial glands w e r e similar to those o f the Day 7 and 8 uteri.

D a y 7 ( A c c . N o s . 8635 a n d 8637) Necrosis o f all the septal tissue o f the caruncles had occurred except for the large arterioles and the basal hyaline zone in one e w e . T h e septal mass including the arterioles was necrotic in the other e w e . Focal ar­ eas o f epithelial proliferation w e r e present in the hya­ line zone. A zone o f proliferation o f stromal tissue was located under the zone o f hyaline connective tis­ sue. T h e vascular stalks o f the caruncles w e r e very edematous. T h e surface epithelium and the zona compacta were arranged in low, wavy folds. N u m e r o u s macro­ phages were present in the zona compacta, some had vaculoated cytoplasm, and others had brown, coarsely granular cytoplasmic pigment. Dense bands o f collagen fibers w e r e present in few areas under the surface epithelium. T h e endometrial glands had small lumina and con­

D a y 21 ( A c c . N o s . 8673 a n d 8701) T h e necrotic caruncular tissue was still attached in ewe number 8673 and the surface epithelium had not regenerated. T h e necrotic caruncular tissue was de­ tached in e w e number 8701 and the caruncular sur­ faces w e r e completely covered by epithelium. I n this ewe, numerous macrophages and lymphocytes w e r e present in the connective tissue beneath the surface epithelium. A wide zone o f normal-appearing stro­ mal tissue was present in the caruncles o f both ewes. T h e surface epithelium and the compact zone o f the intercaruncular endometrium w e r e arranged in low, broad folds. T h e tops o f the epithelial folds had papillary proliferations. M o d e r a t e numbers o f lym­ phocytes w e r e present in the glandular epithelium, and there w e r e periglandular accumulations o f lym­ phocytes.

Sow

D a y 28 ( A c c . N o s . 8672 a n d 8780) Necrotic caruncular tissue had been eliminated f r o m the uterus and the caruncles w e r e covered by epithe­ lium. A moderate number o f lymphocytes w e r e pres­ ent in the caruncular stroma near the surface epithe­ lium and a few lymphocytes and p i g m e n t e d macrophages w e r e scattered through the rest o f the stroma. Perivascular accumulations o f lymphocytes were found around some o f the arteries in the vascu­ lar stalk. T h e large veins in the stalk had thick collag­ enous walls. N o folding o f the surface epithelium o f the inter­ caruncular endometrium was evident, in contrast to the earlier postpartum uteri. N u m e r o u s , large, multi­ focal foci o f intimately apposed, polyhedral cells with abundant, pale, eosinophilic, finely granular cyto­ plasm w e r e located in the zona compacta. G o l d e n brown pigment granules w e r e present in some o f these cells. T h e nuclei o f the affected cells w e r e simi­ lar to but much larger than those o f the adjacent stro­ mal cells. T h e large cells resembled steroid-produc­ ing cells, but I am not aware o f reports concerning steroid production by the stromal cells o f the zona compacta. A n o t h e r possible explanation for the func­ tion o f the large cells is that they may be phagocytic. Similar cells, r e f e r r e d to as foam cells, have been re­ ported in the human e n d o m e t r i u m . Fechner et al. (1979) described the ultrastructure o f these cells in the uterus o f a 68-year-old w o m a n w h o had been treated with diethylstilbestrol, 5 m g three times a day for 7 years. N u m e r o u s large foam cells, with the ul­ trastructural characteristics o f endometrial stromal cells, w e r e present in the hyperplastic e n d o m e t r i u m . T h e foamy appearance o f the cells was d u e to the presence o f lipid droplets. " T h e droplets w e r e not membrane-limited, and did not appear to originate within any organelle" (Fechner et al, 1979). T h e y stated that "with the exception o f o n e r e p o r t e d case o f pyometra, foam cells have been described to occur only in association with endometrial polyps, hyper­ plasia or adenocarcinoma. T h e s e cells can be viewed as the stromal manifestation o f unopposed estrogen stimulation." T h e y suggested that "the lipid in the stromal cells is synthesized in response to the stimulus o f estrogen." T h e lesion was found in the uterus o f ewe 8672, which also had grossly visible, irregularly shaped, linear white areas in the intercaruncular en­ dometrium. T h e s e gross and microscopic lesions were not seen in e w e 8780. A moderate number o f lymphocytes w e r e present in the surface epithelium, in the basal portion o f the glandular epithelium, and in the surrounding stroma. A few pyknotic cells w e r e present in some o f the glands. A few macrophages containing pale

135

brown cytoplasmic pigment w e r e scattered through­ out the tunica propria.

D a y 35 ( A c c . N o s . 8793 a n d 8798) T h e histology o f the caruncles and intercaruncular tissue was similar to that seen on Day 28. Ewe 8798 had foci o f large foam cells similar to those in e w e 8672.

D a y 42 ( A c c . N o s . 8839 a n d 8878) a n d D a y 49 ( A c c . N o s . 8833 a n d 8870) T h e histology o f the uterus was similar on Days 42 and 49. T h e r e was a slight reduction in the lymph­ ocytic infiltrates from Days 28 and 35. A few large focal accumulations o f hemosiderin-laden macro­ phages w e r e present and w e r e considered to have ac­ cumulated because o f injuries sustained during par­ turition. T h e uteri w e r e not considered to have returned to a normal p r e g r a v i d condition. Uterine involution in the e w e differs from that in the cow in several major respects. It requires a longer period o f time. It is an aseptic, relatively dry process in which the necrotic septal tissue sloughs as an intact mass. T h e cervix remains patent for a longer period than in the cow to permit elimination o f the intact necrotic caruncular material. Sloughed caruncles can be found in the pasture o f b e d d i n g as flat masses o f compact, necrotic tissue, the shape o f which some­ what resembles flukes.

D o e (Goat) T i e l g y et al. (1982) described uterine involution in goats slaughtered in pairs at 0, 24, and 62 hours and 5, 7, 9, 12, 15, 18, 2 1 , 25, 28, 32, and 36 days after parturition. T h e gross changes in the uterus ap­ peared to be similar to those in the postpartum e w e . Culture o f the uterine content and histologic changes in the e n d o m e t r i u m w e r e not mentioned. Baru et al. (1983) presented a brief discussion o f the changes that occur in the caprine uterus during postpartum involution. T h e article was illustrated with color photographs o f uteri at Day 0 through Day 35 following parturition.

Sow Jones (1966) r e c o r d e d the characteristics o f the post­ partum vulvar discharge in sows. " A p a r t from the fluid expelled from the uterus at, and shortly after

136

9. The Uterus: Normal Postpartum Involution

delivery, and in conjunction with expulsion o f fetal membranes, a vulvar discharge persisted for upwards o f a week after parturition in two-thirds o f the sows. T h i s discharge was usually mucoid, rather tenacious, often clear at first, gradually becoming streaked by cream or yellow flecks, until eventually the discharge was o f a uniformly creamy appearance; it was some­ times tinged brown by altered b l o o d . " A variety o f bacteria, including E. coli, hemolytic streptococci, and unidentified diptheroids, were isolated f r o m the vul­ var discharge o f 17 clinically normal, postpartum sows. It was emphasized that "care must be exercised in attributing significance to these organisms as causal agents o f puerperal disease." T h e gross and microscopic changes in the involu­ ting uterus o f the postpartum sow have been de­ scribed by Palmer et al. (1965a,b) and Graves et al. (1967). A c c o r d i n g to Palmer et al. (1965a), "the uter­ ine weight and length data indicate that the uterus o f the sow has involuted by 21 to 28 days after parturi­ tion." T h e length o f the uterus decreased from ap­ proximately 240 cm on Day 1 to 120 cm o n Day 28. T h e uterine weight decreased from about 2725 g on Day 1 to 244 g on Day 28. Graves et al. stated that "myometrial involution appears to have been the re­ sult o f both cell destruction and atrophy o f the mus­ cle cells and interspersing connective tissue." Palmer et al. (1965b) conducted histologic exami­ nations o f the ovaries, uterus, uterine tubes, cervix, and vagina from 40 lactating sows slaughtered at 1, 3, 7, 14, 21, 28, 35, 42, and 62 days postpartum. T h e y reported that " A t one day postpartum, the gland cells were only 12 to 15 microns high and most w e r e vacu­ olated with shrunken and pyknotic nuclei, thus pres­ enting a lacy appearance." T h i s appearance o f the glandular cells persisted throughout the 8-week lacta­ tion period. T h e surface epithelium at Day 1 was low columnar to cuboidal and measured 10 to 12 μιη in height. T h e uterine lining was folded and the tunica propria was edematous. A t Day 7 postpartum, the surface epithelial cells were 5 to 6 μπι high and had deeply staining cytoplasm and pyknotic nuclei. N u ­ merous mitotic figures were present in focal areas, in­ dicating regeneration o f the epithelium. N u m e r o u s leukocytes w e r e present in the stroma underlying the epithelial surface, and the edema o f the tunica pro­ pria had subsided considerably. T h e surface epithe­ lium was 15 to 20 μπι high and pseudostratified at Day 14. N u m e r o u s leukocytes w e r e migrating through the surface epithelium and w e r e present in the subepithelial stroma. A t Day 21 the surface epi­ thelial cells were pseudostratified and up to 25 μπι high. T h e leukocytic migration into the uterine lu­ men had subsided. Relatively little change was noted in the epithelium throughout the rest o f lactation.

Mare Ginther (1979) defined the postpartum interval or Puerperium in the mare as "the interval f r o m partu­ rition to the return to a condition conducive to the initiation and maintenance o f another pregnancy. T h e uterus involutes during this time and the ovaries change from a relatively quiescent to an active state." H e stated that the " R e p o r t e d mean lengths o f the in­ terval from parturition to the start o f the first post­ partum estrus are generally given as seven to nine days, and the great majority o f mares ( > 9 0 % ) begin estrus within five to 12 days." A n d r e w s and M c K e n z i e (1941) recorded the first detailed description o f the histologic changes in the uterine mucosa o f the mare following parturition. T h e y reported that the uterus o f only one out o f nine mares had returned to a normal pregravid state on the first day o f estrus. T h e y stated that " I n some cases the mucosa appeared to be completely restored to the farrow (pregravid) condition by the third o r fifth day o f estrus, and in others involution seemed to continue until about the fifth day o f the interestrual period." Gygax et al. (1979) investigated the bactériologie, histologic, and endocrinologie changes associated with postpartum involution o f the uterus in seven mares. Samples o f cervical and endometrial content were cultured for bacteria, endometrial tissue was collected for biopsy, and blood plasma was assayed for progesterone levels. Progesterone was "non-de­ tectable from the day after parturition until the rise, usually associated with ovulation and the formation o f the corpus luteum." Beta-hemolytic streptococci and coliform bacilli w e r e recovered throughout the experimental period, which extended through Day 32 postpartum. N o correlation was found between positive cultures o f endometrial swabs and histologic evidence o f inflammation, and they suggested that the frequent swabbing o f the endometrium and the taking o f biopsy specimens may have caused contami­ nation o f the endometrium. By Day 1 postpartum, the endometrial glands w e r e distended and the stro­ mal tissue was edematous. T h e microcaruncles ex­ tended from the luminal surface into the stratum spongiosa. T h e epithelium o f the microcaruncles had cytoplasmic vacuolization and focal areas o f karyorrhexis. H e m o r r h a g i c and nonhemorrhagic micro­ caruncles w e r e present in the early postpartum period. Some o f the maternal crypts underwent cyto­ plasmic vacuolization, karyorrhexis, and cellular lysis while others involuted by shrinkage o f the maternal epithelial cells and collapse o f the cryptal lumina, re­ sulting in shrinkage o f the entire microcaruncle. Most o f the microcaruncles underwent involution without an inflammatory reaction. T h e microcaruncles w e r e

Bitch

no longer evident by Days 6 o r 7 postpartum except f o r some "small focal remnants consisting o f condensed stroma and crypts lined by contracted o r vacuolated epithelial cells. . . . A f t e r Day 7 the sites o f the f o r m e r microcaruncles w e r e marked either by areas o f stra­ tum compactum o f low cell density o r by aggregations o f macrophages" ( G y g a x et al., 1979). T h e e n d o m e ­ trium appeared to be quite normal by Day 14 "except for occasional slight pleomorphism o f the luminal epi­ thelium, the sporadic occurrence o f inflammatory changes and the presence o f foci o f siderocytes." Steven et al. (1979) investigated the ultrastructural features o f the placenta and postpartum uterus o f the mare. T h e y concluded that "uterine involution is well advanced by the 3rd and 4th days postpartum and the changes are usually complete by the oestrous, 7 to 10 days after parturition." Vandeplassche et al. (1983) stated that involution o f the equine uterus starts immediately following ex­ pulsion o f the foal and "is characterized by a rapid and marked contraction o f the uterus, the cervix, the vagina and the broad ligaments. Consequently, the size o f the genital tract rapidly regresses so that about 12 hours postpartum, the uterine horn that was preg­ nant is not m o r e than 1.5 times the size o f the non­ pregnant horn." T h e weight o f the uterus changed very little during the first 2 days following parturi­ tion. " T h e uterus and cervix o f ten mares, each o f which died o r w e r e slaughtered within two days post­ partum, weighed between 7 and 9 kg. . . . A b o u t Day 8 postpartum, the uterine weight is about 2 kg" ( V a n ­ deplassche et ai, 1983).

Bitch A n d e r s o n and Simpson (1973) described the histol­ ogy and Al-Bassam et al. (1981) r e c o r d e d the gross and microscopic changes in the canine uterus during normal postpartum involution. T h e following de­ scription is in reference to the latter report. During the first week following parturition, small longitudinal folds w e r e present in the serosa o f the edematous, dilated uterus. T h e placental sites w e r e rough, granular, and covered by dark b r o w n mucus and blood clots. T h e mucosa between the placental sites was folded and covered by dark b r o w n mucus. A gradual reduction in the size o f the uterus oc­ curred during the second and third weeks. T h e pla­ cental sites w e r e gray-tan and contained blood clots. T h e entire mucosal surface was covered by dark brown mucus. T h e uterus was much smaller by the fourth week. T h e placental sites w e r e gray-tan and contained 2- to 4-mm gray nodules with a few small petechial hemor­

137

rhages and blood clots. T h e interplacental e n d o m e ­ trium was covered by clear mucus. During the fifth to eighth weeks, the size o f the uterus was reduced, and it reached its smallest size by the eighth week. T h e numbers and size o f the gray nodules in the pla­ cental sites w e r e reduced. T h e uterine horns w e r e uniform in shape by the ninth week, and the placen­ tal sites w e r e differentiated from the rest o f the endo­ metrium by their b r o w n color.

P l a c e n t a l Sites I n regard to the histology o f the postpartum uterus, Al-Bassam et al. (1981) stated that "after separation o f the placenta, the basal glandular zone was the only viable and intact layer remaining. A t the place o f pla­ cental separation o v e r the basal glandular zone, a ne­ crotic mass was observed with a few intact, large and foamy epithelial cells scattered o n the surface as an interrupted single layer." T h e necrotic mass consisted o f "remnants o f fetal placenta, fragments o f the sepa­ rated spongy layer, fibrin, erythrocytes, necrotic thrombosed blood vessels and nuclear debris." L a r g e acidophilic, polygonal cells with o n e to two large nu­ clei w e r e present in the lamina propria. Many o f these cells had pyknotic nuclei and vacuolated, baso­ philic cytoplasm. T h e y stated that "these cells were considered to be either decidual cells (maternal) or trophoblastic cells (fetal), but d u e to their greater sim­ ilarity to decidual cells have been designated as decid­ ual cells." T h i s conclusion may not be warranted. I n cases o f subinvolution o f placental sites, these cells persist and are invasive in some cases, which suggests that they are trophoblastic cells. Immunohistochemical studies should be conducted to establish the true identity o f the large acidophilic cells. Mossman (1987) stated that "Because nothing is known o f the function o f these cells in carnivores, and they are not in the position o f typical decidua, I consider the term d e c i d u a l cells' unfortunate. . . . Until m o r e is known about these cells and a m o r e ac­ curately descriptive term can be coined, M a t e r n a l gi­ ant cell' seems preferable." Al-Bassam et al. (1981) reported that lobulated masses o f collagen f o r m e d in the placental sites dur­ ing the second week and small hemorrhages and scat­ tered mononuclear cells w e r e present in the lamina propria. Most o f the "decidual" cells w e r e degener­ ate. T h e amount o f collagen covering the placen­ tal sites increased during the third week. M o n o n u ­ clear cells, consisting o f macrophages, lymphocytes, and plasma cells, w e r e greatly increased in the lamina propria. T h e endometrial glands contained cellular debris and erythrocytes. A few degenerate

138

9. The Uterus: Normal Postpartum Involution

"decidual" cells w e r e present in only two out o f eight uteri. T h e lobulated masses o f collagen in the placental sites reached their largest size by the fourth week. T h e surface o f the masses was necrotic and hemor­ rhagic. T h e persisting surface epithelium consisted o f foamy, columnar epithelial cells. T h e endometrial glands contained mucus and sparse necrotic debris. A pronounced mononuclear cell infiltrate was pres­ ent in the lamina propria. Al-Bassam et al. (1981) stated that "by the begin­ ning o f the fifth week, the last and most important stage o f placental site involution started with the mas­ sive denudation o f the collagen masses into the lumen. . . . T h e area o f detachment was soon regen­ erated and covered by a single layer o f columnar epi­ thelial cells." Macrophages, lymphocytes, and a few plasma cells w e r e present around the uterine glands and under the surface epithelium. "Changes similar to those observed during the fifth week w e r e seen during the sixth and seventh week postpartum but were m o r e prominent. Most o f the collagen masses were detached from the endometrium and found in the uterine lumen" (Al-Bassam et al., 1981). T h e sloughing o f necrotic tissue was complete by the ninth week, "but the regeneration o f endometrial epithelium continued from the mouth o f the uterine glands and from the regenerated epithelial cells on the surface. T h i s process continued until the end o f the twelfth week when the whole endometrium was lined by a single layer o f small cuboidal o r columnar cells with basophilic cytoplasm and darkly stained basal nuclei" (Al-Bassam et al., 1981). T h e placental sites were brown o w i n g to the presence o f hemosiderin-laden macrophages.

I n t e r p l a c e n t a l Site E n d o m e t r i u m During the first week, primary and secondary folds o f the surface epithelium w e r e present. T h e epithe­ lial cells had a foamy cytoplasm due to the presence o f lipid droplets. T h e lamina propria was edematous and contained a few lymphocytes and plasma cells. "By the fourth week, massive sloughing o f epithelial cells (surface epithelium) occurred into the lumen" (Al-Bassam et al., 1981). T h e number o f mononuclear cells increased in the lamina propria, which was less edematous. Some o f the endometrial glands w e r e slightly dilated while the rest w e r e small and lined by cuboidal to low columnar epithelial cells. Sloughing o f the surface epithelium continued during the fifth and sixth weeks, and only small folds o f foamy cells covered the endometrium. N u m e r o u s fibroblasts, macrophages, plasma cells and a few neu­ trophils w e r e present in the lamina propria. Exfoliation o f degenerate, foamy, surface epithe­

lial cells and regeneration o f epithelium from the necks o f endometrial glands continued during the seventh and eighth weeks. "By the ninth week, many areas o f the endometrium w e r e replaced by a single layer o f small cells with basophilic staining cyto­ plasm. . . . by the end o f the twelfth week the whole e n d o m e t r i u m was lined by a single layer o f small cu­ boidal or columnar cells with basophilic staining cyto­ plasm" (Al-Bassam et ai, 1981). T h e authors con­ cluded that 12 weeks are necessary for completion o f uterine involution in the bitch.

Queen Dawson (1946) described the histologic changes that occur during postpartum involution o f the feline uterus. Following parturition the placental sites con­ sisted o f residual connective tissue o f the lamina pro­ pria and the bases o f the uterine glands. T h e inter­ placental site endometrium had a c o m p l e x luminal surface "composed o f papilliform and plate-like pro­ jections" that had d e v e l o p e d during pregnancy.

P l a c e n t a l Sites T h e basal portion o f the endometrium, which re­ mained after delivery o f the placenta, was infiltrated with neutrophils and macrophages. Replacement o f the surface epithelium occurred by proliferation o f the basal portions o f the endometrial glands and, to a lesser extent, by in-growth o f epithelium from the interplacental site endometrium. " L a r g e , multinucle­ ated masses, with densely stained and closely g r o u p e d nuclei, w e r e frequently found on the surface o f the healing e n d o m e t r i u m . . . these represent vestiges o f the implantation reaction and some persisted in the endometrium until at least 15 days after parturition" (Dawson, 1946). Dawson concluded that "these multi­ nucleated elements are probably identical with the symplasmal masses o f the cat's placenta described by Wislocki and Dempsey (1946)."

I n t e r p l a c e n t a l Site E n d o m e t r i u m Gros (1935) reported that a leukocytic infiltration o f the e n d o m e t r i u m o f the cat occurs during the last weeks o f pregnancy. T h e leukocytic infiltrate in­ creases and the surface epithelium degenerates after parturition. H e stated that the uterus is usually free o f cellular debris at the end o f the sixth day. A c c o r d i n g to Dawson (1946), "the time o f onset and d e g r e e o f desquamation o f the surface epithe­ lium w e r e variable. Some o f the tips o f the projections exhibited advanced involution as early as ten hours after delivery o f the last kitten, although intact epi-

Bibliography

thelium was found in some locations as late as 48 hours postpartum." I n some o f the low folds, involu­ tion occurred without sloughing o f the epithelium. T h e endometrial glands w e r e dilated at the termi­ nation o f pregnancy. S o m e o f the glands w e r e empty and others contained acidophilic material. " N u m e r ­ ous mitotic figures w e r e present in the glandular epi­ thelium at ten hours after delivery, the earliest post­ partum stage studied. A t the end o f the sixth day, the surface o f the uterus was completely covered by a low cuboidal epithelium" (Dawson, 1946). Dawson stated that "after the end o f the first post­ partum week the changes in the e n d o m e t r i u m be­ came almost entirely restorative rather than retro­ gressive." T h e uterine glands increased in length and numbers, and the stroma transformed f r o m a loose fibrous tissue into a compact cellular stroma. Ovarian follicles began to d e v e l o p at the end o f the second postpartum week in nonlactating cats, and "the uterus soon regained its normal appearance and size. T h e cornua lost their flattened f o r m and became cylindrical." Estrus was observed in two non-lactating cats at the end o f the fourth postpartum week. Dawson also stated that " A f t e r the beginning o f the fourth week, both the m y o m e t r i u m and the e n d o m e ­ trium exhibited progressive involution and these ret­ rograde changes continued until lactation ceased." T h e uteri at this time resembled those o f cats that had been castrated for comparable periods. T h e "hyperinvolution" was associated with ovarian inactivity dur­ ing lactation.

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