Decidual Cell Reaction and Endometritis in a Guinea Pig.

Decidual stromal cells are specialized cells in the endometrium essential for the implantation and maintenance of pregnancy, preventing fetal rejection by the maternal immune system.1 They are thought to originate from fibroblast-like cells within the endometrium, which maintain their progesterone receptors in the presence of progesterone.1 Decidual cell reaction is a focal, nonneoplastic, proliferative response of stromal endometrial cells histologically similar to decidua implantation sites.2 Referred to as a deciduoma in earlier human literature because the lesion was originally regarded as neoplastic, the term pseudo-placentational endometrial hyperplasia has been proposed more recently to describe the deciduoma/decidual reaction.3 Spontaneous as well as experimentally induced decidual cell reactions have been reported in various species of animals including mice, rats, hamsters, guinea pigs, rabbits, and dogs.1,3–21 Herein, we report a case of decidual cell reaction accompanied by endometritis in a guinea pig. Case Report A 7-month-old female, research-naive, tricolor, strain 13 guinea pig, born in-house, with no previous significant health history was noted to have a persistent vaginal discharge. The animal was part of a strain 13 guinea pig closed breeding colony housed in a National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH; Bethesda, MD) animal facility accredited by AAALAC International. The female guinea pig was paired with a male but had not produced pups. The animal was housed and cared for according to the Guide for the Care and Use of Laboratory Animals, Public Health Service Policy on Humane Care and Use of Laboratory Animals, the Animal Welfare Act, and Animal Welfare Act Regulations22–24 and was enrolled in an IACUC-approved breeding protocol. Standard husbandry procedures included housing in ventilated microisolation cage setups (Thoren Caging Systems, Hazleton, PA) with autoclaved paper-based bedding (Teklad 7089 diamond soft bedding; Envigo, Indianapolis, IN), food (LabDiet 5025; LabDiet, St. Louis, MO), and tap water ad libitum. In addition, fresh fruits (apple and orange slices), vegetables (cabbage), and/or food treats (Bio-Serv, Flemington, NJ) were provided at least once a week. A dumbbell and tube were provided per cage as environmental enrichment. The colony was tested annually for specific pathogens and found free of lymphocytic choriomeningitis, pneumonia virus of mice, reovirus 3, Sendai virus, and simian virus 5. Culled animals were also tested and found free of ectoparasites and endoparasites, except for intestinal nonpathogenic flagellates. On physical examination the guinea pig had a soft mass in the lower abdomen accompanied by serosanguineous vaginal discharge of 2-day duration. Due to a poor prognosis, the animal was euthanized using CO2 overdose, as per the AVMA guidelines on euthanasia, and the carcass was submitted for pathologic evaluation.25 At necropsy, the left uterine horn was markedly enlarged and purple (Figure 1A). Upon opening the left uterine horn, a 2.5- by 2.5- by 8-cm soft amorphous tissue mass was found (Figure 1B). The mass was red with darker areas and resembled an autolyzed fetus. The right uterine horn was mildly enlarged and congested. The spleen was moderately enlarged. All other organs were within normal limits. Tissue samples were fixed in 10% neutral buffered formalin, paraffin embedded, and processed routinely for histopathologic examination. In addition, uterine tissue and vaginal discharge samples were collected aseptically and submitted to the NIH Division of Veterinary Resources Microbiology Laboratory for routine bacteriological culture, isolation, and sensitivity tests. Light microscopy examination showed that the mass had dense areas containing stromal cells surrounded by connective tissue, congested blood vessels, areas of necrosis, hemorrhage, and occasional cyst formation (Figure 1C). Higher magnification showed areas with densely packed stromal cells next to areas of necrosis and hemorrhage (Figure 1D). The stromal cells were large, round to oval, with abundant eosinophilic cytoplasm, large round nuclei, and in some cases with a prominent nucleolus (Figure 1E). Very few mitotic figures were observed. In some areas, bacteria, both rods and cocci, were noted. Histologic examination of the left uterine wall showed increased thickness caused by a polymorphonuclear cell inflammatory infiltrate (Figure 1F). The right uterine horn was congested and contained multifocal small cysts and mild endometrial hyperplasia. No microscopic abnormalities were noted in other organs. Bacteriological culture and isolation of the vaginal discharge revealed a mixed infection with Escherichia coli, Bacteroides fragilis, Proteus mirabilis, Enterococcus spp., and α-hemolytic Streptococcus spp. while culture and isolation from the uterus revealed a mixed infection with E. coli, B. fragilis, Pseudomonas aeruginosa, and Globicatella sanguinis. The pathology findings were consistent with decidual cell reaction and endometritis.

On histologic examination, the left uterus in this guinea pig showed a proliferative response of stromal endometrial cells similar to decidua implantation sites and consistent with the diagnosis of decidual cell reaction. The lesion can be induced experimentally in ovariectomized guinea pigs by daily progesterone treatment followed by minute amounts of estradiol.11 Focal decidualization in nonpregnant guinea pigs may also occur associated with primary uterine neoplasia, intrauterine trauma, or irritation.9,12,13 In rats, decidual cell reaction has been reported associated with vitamin E deficiency and intrauterine trauma.5,6 In dogs, decidual reaction may be induced by introducing a silk suture into the uteri in the nonpregnant luteal stage of the estrous cycle.17 Canine decidual cell reaction has been induced by intrauterine inoculation of E. coli isolated from a naturally occurring canine pyometra.19 In addition, more recently, decidual cell reactions have been reported associated with pyometra in bitches.20 The presence of bacteria in the uterus of the guinea pig in the present case report suggests this may have contributed to endometritis and, possibly, decidual cell reaction. It may be possible that the female had an abortion during early pregnancy that went unnoticed, or embryonic death, with retained membranes that became infected with enterobacteria. Escherichia coli is the most commonly isolated bacteria from pyometra cases in dogs and cats, followed by Staphylococcus spp. and Streptococcus spp.,26 while Pseudomonas spp., Proteus spp., and Enterococcus spp. are occasionally reported as a cause of pyometra in dogs.26 In humans, B. fragilis, E. coli, Streptococcus spp., and Enterococcus spp. are commonly isolated from uterine infections.27,28 Mixed infections appear to be common in both human and veterinary medicine. All bacteria isolated from the guinea pig in this case have been reported in the literature as a cause of pyometra/endometritis in humans and small animals, with the exception, to our knowledge, of G. sanguinis. Globicatella sanguinis was first reported in 1992 as G. sanguis, a new genus and species of catalase-negative, facultatively anaerobic, gram-positive cocci related to the streptococci.29 In 1997 the species was renamed G. sanguinis and has been occasionally isolated from human patients with meningitis, bacteremia, endocarditis, urinary tract infections, osteomyelitis, and endophthalmitis.30–40 In animals, G. sanguinis infections are even rarer, with only one report of its isolation from lambs with meningoencephalitis.41 Vaginal bleeding is not a common clinical sign in decidual cell reaction. Differentials for female reproductive tract bleeding are diverse and mostly include complications of pregnancy, reproductive tract infections, tumors, or traumatic lesions, endometriosis, systemic conditions, and hormonal and coagulation disorders.42 Decidual cell reactions usually do not require treatment since the lesion in many cases resolves on its own by apoptosis and resorption.13 However, in the case described here, systemic antibiotics may have been beneficial to treat the endometrial infection. These findings suggest decidual cell reactions may occur accompanied by, or a result of, intrauterine infections in guinea pigs. The potential role of bacteria in decidual cell reaction should be further explored in guinea pigs. This is to our knowledge the first report of G. sanguinis infection in a guinea pig. Contributor Notes