Naturally occurring and melengestrol acetate-associated reproductive tract lesions in zoo canids.

As husbandry practices have improved, safe and effective contraception for captive wildlife management has become a necessity. Melengestrol acetate (MGA), a synthetic progestin, is highly effective and has been used in many zoo species. Long-term use of MGA has been associated with uterine lesions in zoo felids, but effects in zoo canids have not been evaluated. This retrospective study documented spontaneously occurring lesions and investigated the impact of MGA on the reproductive health of zoo canids. Reproductive tracts from adult females were submitted by US zoos to the Association of Zoos & Aquariums' Wildlife Contraception Center Health Surveillance Program. Reproductive tracts were sampled and processed for histopathologic examination following standard protocols. Microscopic evaluations were performed without prior knowledge of MGA treatment status. Prevalence of uterine lesions was evaluated and compared between MGA-treated animals (n = 20) and control (untreated) animals (n = 61). Common lesions within the study population as a whole included endometrial hyperplasia (predominantly cystic) (53%), hydrometra (33%), and adenomyosis (25%). Treatment with MGA was a risk factor for endometrial hyperplasia, hydrometra, fibrosis, and adenomyosis. Uterine mineralization occurred exclusively in MGA-treated animals. Results indicate that MGA contraception can lead to lesions that may permanently impair the fertility of females. Therefore, if long-term contraception of zoo canids is necessary, the use of alternate methods of reproductive control such as gonadotropin-releasing hormone (GnRH) analogs or GnRH vaccines that reduce gonadal hormone exposure should be pursued.

Histologic features of mammary carcinomas in zoo felids treated with melengestrol acetate (MGA) contraceptives.

Melengestrol acetate (MGA), a potent synthetic progestin, has been used as a contraceptive in zoo felids since 1975. Mammary gland carcinomas have been linked to MGA treatment in zoo felids, but the histologic features of these tumors and steroid receptor expression have not been described. Zoo felid mammary tumors were requested from participating zoos from 1986 through 1998, and 31 mammary carcinomas from 28 MGA-treated and 3 untreated felids were received. The carcinomas were evaluated on the basis of histologic pattern, tumor grade, and occurrence of metastasis; then features of the tumors were compared to determine if carcinomas in MGA-treated felids differed from those that occur spontaneously. Estrogen- and progesterone-receptor expression was evaluated in 17 of the 31 carcinomas. Of the 31 tumors, 22 (70.9%) had multiple histologic patterns, 29 (93.5%) were high grade, and 28 (90.3%) had metastasized. Within tumors, the tubulopapillary pattern was most common (87.1%, n = 27); solid (61.3%, n = 19), cribriform (38.7%, n = 12), and comedone (25.8%, n = 8) patterns were less common; and the mucinous (3.2%, n = 1) pattern was rare. Both MGA-treated and untreated zoo felids had similar patterns and grades of mammary gland cancer as well as prevalence of metastasis. These results indicate that mammary carcinomas in zoo felids are high grade with a predominant tubulopapillary pattern and aggressive behavior. Five of 17 carcinomas expressed progesterone receptors, and 1 of 17 expressed estrogen receptors. Although more zoo felids with cancer had been exposed to MGA in this study, mammary carcinomas were similar in appearance and behavior in untreated and MGA-treated zoo felids. The association of MGA with the development of malignant mammary gland tumors should be considered when using this contraceptive in zoo felids.

Effect of dietary melengestrol acetate on the incidence of acute interstitial pneumonia in feedlot heifers.

Over a 3-y period, 906,000 cattle were monitored in 23 feedlots in southern Alberta for symptoms of acute interstitial pneumonia (AIP). Plasma, urine, and lung tissue were collected at slaughter from 299 animals clinically diagnosed with AIP and from 156 healthy penmates and analyzed for 3-methylindole (3MI) derivatives and reduced glutathione concentration. From each animal, the left lung was subsampled for histologic examination. Concentrations of glutathione in lung tissue were reduced (P < 0.001) in animals showing clinical symptoms of AIP as compared with their asymptomatic penmates. Animals histologically confirmed as having AIP had higher levels of 3MI protein adducts in blood and lung tissue (P < 0.05) than did emergency-slaughtered animals without AIP. Within feedlots, where pens of heifers were fed either a standard dosage of melengestrol acetate (MGA) or none, the rate of death attributable to AIP was similar between treatment groups, but emergency slaughter after clinical diagnosis of AIP was done 3.2 times more often (P < 0.001) in the MGA-fed heifers than in the group not fed MGA. Use of MGA did not influence glutathione concentration. As growth performance of heifers given steroidal implants may not be improved by feeding MGA, the most cost-effective method of reducing the incidence of AIP-related emergency slaughter in feedlot heifers may be to eliminate MGA from the diet.

Endometrial hyperplasia and mineralization in zoo felids treated with melengestrol acetate contraceptives.

Melengestrol acetate (MGA) contraceptives are widely used in zoo felids to regulate fertility and may have deleterious effects on endometrial health. To determine whether MGA exposure was associated with endometrial disease, the genital tracts of 212 zoo felids (99 MGA treated and 113 control) representing 23 species were evaluated. Adenomatous and cystic hyperplasia were prevalent in both MGA-treated (85%) and control (61%) groups, and the risk of developing these lesions increased with age. Treatment with MGA further increased the risk of developing advanced hyperplasia regardless of dose, and treatment for >72 months significantly elevated that risk, whereas parous animals had a lower risk. Endometrial polyps, fibrosis, adenomyosis, and hydrometra occurred in both MGA-treated and control animals. MGA treatment was associated with an increased risk of hydrometra and mineralization but not of adenomyosis, polyps, or fibrosis after adjusting for advanced hyperplasia. Acute or chronic endometritis were associated with advanced hyperplasia but not with MGA treatment. These results indicate that proliferative and inflammatory endometrial lesions are common spontaneous diseases in zoo cats, and MGA contraceptives increase the risk of some diseases. The association of MGA with endometrial lesions that could impair fertility should be considered when using this contraceptive in genetically valuable felids.

Genital tract smooth muscle tumors are common in zoo felids but are not associated with melengestrol acetate contraceptive treatment.

In a survey of gynecologic lesions in female zoo felids conducted to determine if the widely used progestin contraceptive melengestrol acetate (MGA) had adverse effects, numerous leiomyomas and leiomyosarcomas were detected. This current study aimed to characterize the morphologic features of these tumors, determine their prevalence, and assess if MGA was a risk factor for their genesis. Genital tracts from 219 zoo felids representing 23 species were evaluated, and leiomyomas were detected in 24% of the felids. Leiomyomas were often multiple and occurred in the myometrium, ovary, or adjacent broad ligament. The risk of developing leiomyomas increased with age, but MGA treatment or parity had no effect. Five other felids had leiomyosarcomas. Leiomyosarcomas were distinguished from poorly demarcated leiomyomas by the presence of local invasion, metastasis, and cellular atypia, but necrosis and mitotic rate were not distinguishing criteria. Four of five felids with leiomyosarcomas had been treated with MGA. These results indicate that leiomyomas are common spontaneous lesions in the genital tracts of zoo felids and their genesis is not linked to MGA exposure. Whether progression to malignancy is promoted by MGA warrants further investigation.

Pyometra and uterine adenocarcinoma in a melengestrol acetate-implanted captive coati (Nasua nasua).

A 9-yr and 3-mo-old captive female coati (Nasua nasua) was implanted with melengestrol acetate for contraception for 4.5 yr prior to presentation. During her annual examination, purulent vaginal discharge and a palpably prominent uterus were identified. Ancillary diagnostic tests including hematology, cystocentesis, radiographs, and abdominal ultrasound were consistent with pyometra. An ovariohysterectomy was performed and histologic examination revealed pyometra and uterine adenocarcinoma, similar to pathology that has been associated with melengestrol acetate contraception in felids, canids, and primates. Given the potential association between melengestrol acetate and uterine pathology in this case, we recommend caution with melengestrol acetate use in procyonids.

The effects of melengestrol acetate on the ovaries of captive wild felids.

Melengestrol acetate (MGA) is the most widely used contraceptive in zoo felids, but the mechanism of contraception and the pathologic effects have not been investigated. For this study, the effects of MGA on folliculogenesis were assessed, and the association of MGA with ovarian lesions was evaluated. Comparisons were made among the histopathologic findings in the ovaries from 88 captive wild felids (representing 15 species) divided into three groups: 37 currently contracepted with MGA, eight previously exposed to MGA, and 43 never contracepted. Ninety-one percent of the felids evaluated had tertiary follicles, and no differences were noted between contracepted and uncontracepted cats. Some MGA-contracepted cats also had corpora lutea indicating recent ovulation. These results indicate that folliculogenesis not suppressed by current doses of MGA and ovulation occurred in some cats. Therefore, the contraceptive actions of MGA do not occur by suppressing folliculogenesis, and MGA-contracepted felids likely have endogenous estrogens that may confound progestin effects on the uterus. Cystic rete ovarii was the most common pathologic finding, but they were not more prevalent in MGA-contracepted cats. These findings indicate that MGA is not associated with ovarian disease, including ovarian cancer, in contrast to the uterine lesions noted in MGA-treated cats.