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Ultrasonographic characteristics of the reproductive tract and serum progesterone and estradiol concentrations in captive female red wolves (Canis rufus) with and without reproductive tract disease
Abstract
OBJECTIVE To describe ultrasonographic characteristics of the reproductive tract and serum progesterone and estradiol concentrations in captive female red wolves ( Canis rufus ) with and without reproductive tract disease.
DESIGN Prospective study.
ANIMALS 13 adult female red wolves.
PROCEDURES Wolves with varying parity and history of contraceptive treatment were anesthetized to facilitate ultrasonographic examination and measurement of the reproductive tract and blood collection for determination of serum progesterone and estradiol concentrations in December 2011 and June 2012. Additionally, during the December evaluation, fine-needle aspirate samples of the uterus were obtained for cytologic evaluation. Measurements were compared between wolves with and without reproductive tract disease and between wolves that had and had not received a contraceptive.
RESULTS 7 of 13 wolves had or developed reproductive tract disease during the study. Ranges for measurements of reproductive tract structures overlapped between ultrasonographically normal and abnormal tracts, but measurements for abnormal tracts were generally greater than those for normal tracts. The ultrasonographic diagnosis was consistent with the histologic diagnosis for reproductive tracts obtained from wolves that were sterilized, were euthanized, or died during the study. Cytologic results for fine-needle aspirate samples of the uterus and serum progesterone and estradiol concentrations were unable to distinguish wolves with and without reproductive tract disease. Reproductive tract disease was not associated with parity or contraceptive administration.
CONCLUSIONS AND CLINICAL RELEVANCE The ultrasonographic images, reproductive tract measurements, and descriptions of reproductive tract lesions provided in this study can be used as diagnostic guidelines for the treatment and management of red wolves with reproductive tract disease.
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Pyometra is a serious, life-threatening disease of both domestic and non-domestic species often requiring ovariohysterectomy to preserve the life of the animal. Medical management of pyometra has been successful in domestic and non-domestic species, and the consideration of such treatment is of marked importance in a critically endangered species. Of the canids, the red wolf (Canis rufus) is second only to African hunting dogs (Lycaon pictus) in terms of the prevalence of both cystic endometrial hyperplasia and pyometra. In this report, three red wolves were medically managed for pyometra. Aside from vaginal discharge, none of the wolves exhibited clinical signs, nor were there reflective inflammatory changes in the laboratory findings. All wolves received standard treatment for pyometra, including prostaglandin F2alpha and antibiotic therapy, while one wolf was more aggressively managed with uterine lavage. Pyometra recurred in two of the treated wolves, while the most aggressively managed wolf continues to show ultrasonographic resolution 2 yr posttreatment. Aggressive medical management of pyometra should be considered a treatment option in certain red wolf females, as it may preserve the animal's reproductive potential.
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.
The sensitivity of the pituitary to GnRH in early and late anoestrus and the indirect response of the ovary were investigated in six adult beagle bitches. Plasma concentrations of LH and oestradiol were determined after i.v. injection of graded doses of GnRH (0, 0.01, 0.1, 1, 10 and 100 micrograms kg-1). The responses were measured by the LH and oestradiol concentration profiles over time. The responses of LH and oestradiol were significantly dose dependent (P = 0.002 and P < 0.001, respectively). The responses of LH and oestradiol were significantly higher (P = 0.02 and P = 0.001, respectively) in late anoestrus than in early anoestrus. The responses of LH and the responses of oestradiol were positively correlated (r = 0.97, P = 0.001). It is concluded that during the course of anoestrus in the bitch pituitary sensitivity to GnRH increases while the ovary responds accordingly.
An animal insurance database containing data on over 200,000 dogs was used to study the occurrence of pyometra with respect to breed and age during 1995 and 1996 in Swedish bitches <10 years of age. A total of 1,803 females in 1995 and 1,754 females in 1996 had claims submitted because of pyometra. Thirty breeds with at least 800 bitches insured each year were studied using univariate and multivariate methods. The crude 12-month risk of pyometra for females <10 years of age was 2.0% (95% confidence interval = 1.9-2.1%) in 1995 and 1.9% (1.8-2.0%) in 1996. The occurrence of pyometra differed with age, breed, and geographic location. The risk of developing pyometra was increased (identified using multivariate models) in rough Collies, Rottweilers, Cavalier King Charles Spaniels, Golden Retrievers, Bernese Mountain Dogs, and English Cocker Spaniels compared with baseline (all other breeds, including mixed breed dogs). Breeds with a low risk of developing the disease were Drevers, German Shepherd Dogs, Miniature Dachshunds, Dachshunds (normal size), and Swedish Hounds. Survival rates indicate that on average 23-24% of the bitches in the databases will have experienced pyometra by 10 years of age. In the studied breeds, this proportion ranged between 10 and 54%. Pyometra is a clinically relevant problem in intact bitches, and differences related to breed and age should be taken into account in studies of this disease.
Conservation efforts to preserve the red wolf ( Canis rufus ) have been in progress since the 1970s through the U.S. Fish and Wildlife Service Red Wolf Recovery Program and the Association of Zoos and Aquarium's Red Wolf Species Survival Plan. An ongoing part of this project has been to monitor mortality trends, particularly to look for potential genetic conditions resulting from inbreeding given the small founding population of only 14 individuals. An initial survey was conducted in the 1990s but a comprehensive assessment of the population has not been done since then. This retrospective review evaluates mortality in the population from 1997 to 2012 through analysis of gross necropsy and histology records provided by cooperating institutions that housed red wolves during the time period of interest. Of the 378 red wolves that died during this 15-yr period, 259 animals had gross necropsy records, histology records, or both that were evaluated. The major causes of neonatal death were parental trauma, stillbirth, or pneumonia. Overall, juveniles had very low mortality rates with only 12 wolves aged 30 days to 6 mo dying during the study period. The most common cause of death within the adult populations was neoplasia, with epithelial neoplasms, carcinomas, and adenocarcinomas being the most common types reported. Gastrointestinal disease was the second most common cause of death, particularly gastric dilation and volvulus, inflammatory bowel disease, and gastrointestinal perforations. These findings are in stark contrast to causes of mortality in the wild population, which are primarily due to human-related activities such as vehicular trauma, gunshot, or poisoning. Overall, the captive population has few health problems, but an increase in inflammatory bowel disease in particular warrants further investigation.
The ability to safely and effectively manage reproduction is central to the success of AZA captive-breeding programs. Although the AZA Wildlife Contraception Center routinely monitors contraceptive safety, there have been no studies that compare the effects of contraceptive use to separation of males from females, the other option for preventing reproduction. We used retrospective medical records and pathology reports submitted by AZA and related facilities for the seven AZA-managed canid species to assess rates of uterine pathology relative to female reproductive life histories. Our results showed that the prevalence of both pyometra and endometrial hyperplasia (EH) was associated not only with treatment with the two most common contraceptives (Suprelorin® and MGA implants) but also with the number of years barren (i.e., not producing a litter and not contracepted). Rates of pyometra and EH were especially high in African painted dogs and red wolves, but lowest in swift and fennec foxes. The number of years producing a litter had a low association, suggesting it could be protective against uterine pathology. A more recently developed Suprelorin® protocol using Ovaban® to prevent the initial stimulation phase, followed by implant removal when reversal is desired, may be a safer contraceptive option. These results concerning the relationship between reproductive management and uterine health have important implications for AZA-managed programs, since the unsustainability of many captive populations may be due at least in part to infertility. Managing a female's reproductive lifespan to optimize or maintain fertility will require a reconsideration of how breeding recommendations are formulated. Zoo Biol. XX:XX-XX, 2013. (c) 2013 Wiley Periodicals Inc.
Transcervical endometrial biopsy is a useful tool for obtaining information about uterine health in some species. The clinical application of information gained from histopathological interpretations of endometrial biopsies in the bitch has not been validated. We hypothesized that transcervical endometrial biopsy samples would be as diagnostic as full-thickness uterine sections in identifying cystic endometrial hyperplasia (CEH), inflammation and periglandular fibrosis. Endometrial biopsies were obtained from 20 female adult dogs. Vaginal swabs, gross appearance of the vulva and vaginal tract, and serum progesterone values were used to determine the stage of the oestrous cycle at the time of sampling. The uteri were removed between 1 and 6 days after the biopsy procedure, and full-thickness sections were collected from each uterine horn and ovary and processed for histopathology. Two pathologists, blinded to the origin of each sample, compared full-thickness sections from the excised uteri to the biopsy samples collected via the transcervical technique. Pathologic features noted included: CEH, inflammation and periglandular fibrosis. Pathological diagnoses obtained from the biopsy sections were compared with those obtained from the full-thickness sections, as well as comparing diagnoses between the two pathologists, using McNemar's test. Of the 59 total biopsy samples obtained, 54 were considered diagnostic. All stages of the canine oestrous cycle were represented (anoestrus, proestrus, oestrus and dioestrus). Pyometra was not noted in any of the transcervical biopsy sections, but was noted in many of the full-thickness sections collected from dogs in dioestrus, suggesting either that biopsy is not a sensitive indicator of pyometra or that the procedure may induce pyometra in dioestrous dogs. Transcervical endometrial biopsy showed similar sensitivity as full-thickness sections in detecting CEH, inflammation and fibrosis. No differences in describing lesions were detected between pathologists.
Reproductive steroid profiles in female (n=13) and male (n=5) red wolves (Canis rufus) were characterized in fecal samples collected during the breeding season (December—May) and over a 1 year period, respectively. Blood samples from females (n=12) also were collected during the periovulatory period for luteinizing hormone (LH) and steroid analysis. High performance liquid chromatography (HPLC) of fecal extracts determined that estradiol and estrone constituted the major and minor forms, respectively, of fecal estrogen metabolites. Although native progesterone was present, pregnane metabolites predominated as the major forms of fecal progestins. HPLC analysis of fecal extracts from males revealed no native testosterone, but rather the predominance of more polar androgen metabolites. Based on hormone profiles and/or pup production, females were classified as pregnant (n=3), ovulatory-nonpregnant (n=9), or acyclic (n=3). Longitudinal monitoring of females indicated no pregnancy-specific differences in concentrations of either fecal progestagen or estrogen metabolites compared to ovulatory-nonpregnant individuals; however, baseline progestagen concentrations were consistently elevated in acyclic females. There was good correspondence between serum and fecal steroid concentration during the periovulatory period. A rise in serum estrogens preceded the ovulatory LH surge which was then followed by a significant progesterone rise during the luteal phase. In males, changes in fecal androgen metabolite concentrations coincided with photoperiod fluctuations, increasing in late autumn and reaching peak concentrations during mid- to late winter just before the start of the breeding season. Collectively, these results serve as a database of ovarian and testicular endocrine events in this species, which can be utilized in population management and application of assisted reproductive technologies. Zoo Biol 21:321–335, 2002. © 2002 Wiley-Liss, Inc.
Long-term studies of megestrol acetate and chlormadinone acetate in 100 female dogs are in progress. Doses of zero, one, 10 and 25 times the expected human dose of megestrol acetate and 25 times the expected human dose of chlormadinone acetate (on a milligram per kilogram body weight basis) are being given daily. During the first 4 years, eight dogs from each of the five groups were killed. The principal gross findings included enlarged uteri with mucoid material in the lumina, mammary development in dogs given middle and high doses of megestrol acetate and chlormadinone acetate, and thickened gallbladder walls in dogs given high doses of each. Histologic evaluation showed inhibition of ovulation for progestogen-treated dogs and suppression of ovarian follicular development with the high doses. Cystic endometrial hyperplasia was slight in the low-dose dogs and moderate to severe in most of the high-dose dogs; a few also had ulcerative endometritis and pyometra. The mammary glands of dogs given the middle and high doses produced lobules, acini, and secretion exceeding natural metestrus. Slight to marked cystic mucinous hyperplasia occurred in the gallbladders of most dogs given the high doses. Tow high-dose megestrol dogs had clinical signs and microscopic pancreatic, renal, and ocular changes indicative of diabetes mellitus.
Immediate and long-term outcomes of prostaglandin F2 alpha treatment for canine pyometra were studied in 10 bitches. Examination of pretreatment uterine biopsy specimens, taken for histopathologic diagnosis and classification of disease severity, revealed either type III or IV pyometra. Dinoprost tromethamine (0.25 or 0.5 mg/kg of body weight, SC) was given once daily for 3 days. Bitches were bred at the first posttreatment estrus and monitored for a minimum of one year. When pure cultures of Escherichia coli (n = 3) or Staphylococcus aureus (n = 1) were obtained from the vagina, these bacteria also were found in the uterus. Pretreatment WBC counts often did not reflect the severity of histopathologic findings in the uterus, but posttreatment WBC counts were useful in monitoring response to treatment. Four bitches produced a litter within one year of treatment. Four bitches (40%) had recurrence of pyometra within one year of treatment, and these same bitches had another recurrence after an additional prostaglandin treatment. Three additional bitches had a recurrence by 27 months after therapy, establishing a total recurrence rate of 77% (7/9). Results suggested that subclinical disease may persist after treatment, with clinical recurrence during diestrus. Despite the high recurrence rate, it was concluded that this treatment is a practical treatment for canine pyometra when reproduction is desired.
Ejaculates of the red wolf (Canis rufus) were evaluated immediately after collection and freeze-thawing to initiate a reproductive database for this endangered species. Electroejaculates from 13 adult red wolves collected during the breeding season (February-March; n=25; 1-3 collections/male) had a mean volume of 4.7+/-0.7 ml, 146.5+/-25.7 x 10(6) spermatozoa/ml and 71.2% motile spermatozoa. The mean proportion of cells with normal morphology was 73.6+/-3.2% (range, 20.3-93.7%), with 64% of ejaculates (16/25) containing 70-90% normal spermatozoa. The four most predominant abnormalities were a coiled flagellum (8.1%), a bent flagellum (4.7%), a bent midpiece with no cytoplasmic droplet (3.3%;), and a detached head defect (6.4%). After cooling in glycerolated extender, semen was frozen using a pelleting method on dry ice before plunging into liquid nitrogen. Pellets were thawed in phosphate buffered saline and examined for % sperm motility, normal morphology, viability and intact acrosomes. There was a decline (P < 0.05) in sperm motility (approximately 40%) and percentage of normal sperm (11.9%) after freezing, but no change in the proportion of viable cells. After freezing, there was a marked decline (P < 0.05) in the proportion of intact acrosomes from 74.5% to 55.5% which was accompanied by an increased proportion (P < 0.05) of partial acrosomes from 11.9% to 35.8%. These data demonstrate that, although red wolf spermatozoa can survive freeze-thawing using a technique common for domestic dog sperm, the finding of significant acrosome damage reveals (1) likely species specificity in the Canis genus and (2) the need for refining sperm cryopreservation technology for the red wolf.
Through the Red Wolf Species Survival Plan, the captive red wolf (Canis rufus) population was developed with the intent of reestablishing wild populations. One part of the plan was a survey for diseases that might occur as a result of population homogeneity or that might impede breeding success and reintroduction. For this survey, complete necropsies and histopathologic analyses were performed on 62 red wolves from 1992 to 1996. Major causes of 22 neonatal deaths were parental trauma, parasitic pneumonia, and septicemia. Common neonatal lesions included pododermatitis and systemic ascariasis. Cardiovascular anomalies and systemic parasitism were found in two juveniles. Causes of death in the 38 adults included conspecific trauma, neoplasia, or gastrointestinal diseases such as necrotizing enteritis, intestinal perforation, and gastric volvulus. Lymphosarcoma represented 50% of the fatal neoplasms. Three adults died from cardiovascular failure or hyperthermia during handling, and several adults were euthanized for suspected genetic diseases. Overall, the captive population had few significant health problems, but population fitness might be improved by continued removal of potentially deleterious genes from the breeding population and by modifying the husbandry of neonates and adults.
Transcervical collection of endometrial tissue specimens is a valuable and well established tool for the diagnosis of reproductive disorders in cows, mares and women, but it is not used currently in bitches. Endometrial biopsy samples were collected by transcervical cannulation from the cranial uterine body at defined stages of the oestrous cycle using biopsy forceps. In study 1, the histology of 45 biopsy specimens taken from 23 Beagle bitches were compared with larger tissue samples collected post mortem. For further evaluation of representative biopsy specimens, the expression of oestrogen and progesterone receptors was determined. Only 31.1% of the biopsy samples taken from bitches could be evaluated and they showed stroma, capillaries, luminal epithelium, glandular ducts and apical glands; however, basal glands and myometrium were not observed. Biopsy findings were in agreement with the diagnosis of the uterine specimens concerning endometrial differentiation, inflammatory and degenerative lesions. The expression of oestrogen and progesterone receptors was slightly lower in the biopsy samples. In study 2, a total of 49 serial biopsy samples were taken from 12 Beagle bitches. In eight bitches, the manipulation resulted in a haemomucometra. Treatment with PGF2 alpha and antibiotics led to a clinical cure in five of these dogs, two of which were mated successfully during the next oestrus. Three animals had to undergo ovariohysterectomy. Owing to the small proportion of biopsy specimens that was suitable for analysis and the high risk of biopsy-related endometritis, transcervical biopsy collection cannot be recommended as a routine technique in bitches.
Continuous low-dose administration of a GnRH analogue postpones oestrus in bitches and suppresses reproductive function in dogs. A new drug delivery formulation that could enhance the practicality of this approach for the control of reproduction has been developed. The objective of the present study was to determine whether this method of delivery could, by sustained release of the GnRH analogue deslorelin, act as a reversible anti-fertility agent in domestic male and female dogs for periods exceeding 1 year. Several long-term studies were performed, which monitored reproductive function in 30 dogs and 52 bitches. Suppression of reproductive function in male dogs was dose-related. Spermatogenesis was suppressed for more than a year in 14 of 16 dogs that received doses of > 0.25 mg deslorelin kg-1. In females, postponement of oestrus for periods of up to 27 months was observed, but there was no relationship between the stage of the oestrous cycle at the start of treatment and the duration of efficacy. Treatment-induced effects on fertility were reversible in both sexes. In summary, sustained release deslorelin implants were shown to elicit reversible long-term reproductive control in male and female domestic dogs.
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.
Accurate prediction of parturition date is useful for clinical management of canine parturition. For nearly all normal canine pregnancies, parturition occurs 64-66 days from the LH peak, the timing of which cannot be differentiated from the initial sharp rise in serum progesterone (P4) concentrations. We sought to determine by retrospective analysis if prebreeding serum progesterone concentrations could accurately predict parturition date. Serum progesterone concentrations recorded as serial samples from 63 bitches (19 breeds) were analyzed. Progesterone concentrations were measured by radioimmunoassay (RIA) or chemiluminescent immunoassay (CLIA). The CLIA method was validated for use in determining P4 concentrations in canine serum and results were comparable to those obtained with RIA. Bitches were grouped by nonpregnant body weight (BW) and litter size (LS). Day 0 (D0), the day of preovulatory rise in serum P4, was defined as the day that P4 concentration rose to > or =l.5 ng/ml and was at least twice the baseline concentration. The predicted parturition date, 65 days following the day of preovulatory rise in serum P4 (D65), was compared to actual parturition date, the day the first pup was delivered. We determined that mean P4 concentration at D0 for all BW groups was 2.02+/-0.18 ng/ml and there was significant variation in P4 concentrations between BW groups after D1. In addition, we determined that the accuracy of parturition date prediction within a +/-1, +/-2, and +/-3 day interval using prebreeding serum progesterone concentrations was 67, 90, and 100%, respectively, and that the accuracy was not affected by body weight or litter size.
The aim of this study was to determine the therapeutic success of the medical treatment of canine pyometra with the antigestagen aglepristone and to document the recurrence rate in relation to the time interval after treatment with antigestagens. In 48 (92.8%) of the 52 treated bitches, healing could be achieved within the first 3 weeks after the treatment had been started. One bitch died as a result of renal insufficiency; in three bitches there was no emptying of the uterus, so ovariohysterectomy became necessary. In these three patients, ovarian and endometrial cysts were present. Forty-one bitches could be followed up for 3 months. Four animals developed a recurrence (9.8%). In three bitches ovarian cysts and cystic endometrial hyperlasia could be found intra operationem. The development of 37 bitches could be followed for at least 1 year. Seven animals developed a pyometra again (18.9%). Two received a repeated treatment with aglepristone and have been free from recurrence for over 12 months. In 37 animals data on the subsequent sex cycles are available. In 22 bitches next heat started at the expected time, in seven animals heat started too early. In eight bitches the period of anoestrus was prolonged. Five of the six bred bitches delivered at least one litter. The presented data show that treatment of pyometra by aglepristone results in a high healing rate. The recurrence rate can be minimized by the selection of bitches without ovarian cysts and cystic endometrial hyperplasia.
Cystic endometrial hyperplasia-pyometra complex is the most frequent and important endometrial disorder encountered in bitches. The pathogenesis of the disease is related to the activity of progesterone [Feldman and Nelson, Canine and Feline Endocrinology and Reproduction (1996) W.B. Saunders, Philadelphia]. Cystic endometrial hyperplasia (CEH) is an abnormal response of the bitch's uterus to ovarian hormones [De Bosschere et al. Theriogenology (2001) 55, 1509]. CEH is considered by many authors to be an exaggerated response of the uterus to chronic progestational stimulation during the luteal phase of the oestrous cycle, causing an abnormal accumulation of fluid within the endometrial glands and uterine lumen (De Bosschere et al. 2001). The resulting lesions of pyometra are due to the interaction between bacteria and hormones. The aim of this study was to evaluate if transabdominal uterine ultrasonography can be a useful and reliable diagnostic method to confirm Dow's [Veterinary Record (1958) 70, 1102] and De Bosschere's histopathological classification of CEH-pyometra complex. The study was carried out on 45 bitches with pyometra, 10 purebreds and 35 crossbreeds, 1-15 years old, 20% of which had whelped at least once. None of these animals had received exogenous oestrogen or progesterone treatment. On admission the 45 animals were in the luteal phase of the oestrus cycle. Clinical signs, blood parameters, uterine ultrasonography, bacterial swabs and uterine histopathological results were recorded. Results suggest that ultrasonographic examination is a useful and reliable tool for the diagnosis of cystic endometrial hyperplasia.
Gonadotropin releasing hormone (GnRH) has long been recognized as a potential target for the control and management of fertility in female animals. Attempts to apply GnRH-based technology to manage fertility have focussed on the development of GnRH agonists, antagonists and vaccines. All of these methods have potential, but the widespread application of these technologies has been limited to date. The greatest advance in the use of GnRH-based technology for long-term fertility control in recent years has been the development and commercialization of depot formulations that release GnRH agonists for periods of up to 1 year. These products have a broad range of potential applications in production and domestic animal management. The further development and commercialization of GnRH vaccines has been hampered by the variability of response between individual animals. The need to use adjuvant and multiple boosters also make this a less attractive option than the current GnRH agonist technology. However, GnRH vaccines have the advantage that they do not induce the initial stimulatory response that follows GnRH agonist administration. GnRH antagonists and GnRH-toxin conjugates show promise but are in an earlier phase of development. To date, no depot or long-acting formulations of antagonists have been developed. GnRH-toxin conjugates have yet to achieve permanent sterilization, but further dose-response trials may advance this approach.
Pyometra, literally meaning pus in the uterus, is a common disease entity of intact bitches. Similar conditions occur, including hydrometra and mucometra [De Bosschere H, Ducatelle R, Vermeirsch H, Van Den Broeck W, Coryn M. Cystic endometrial hyperplasia-pyometra complex in the bitch: should the two entities be disconnected? Theriogenology 2001;55:1509-19]. The exact etiology is unknown; however the repeated and prolonged response to estrogen followed by long intervals of progesterone dominance in the intact bitch leads to hormonally mediated changes in the endometrium. The endometrium changes when impacted by bacterial infiltration; changes in endometrial steroid receptors can result in the clinical syndrome described as pyometra. This paper will describe the signalment, risk factors, prevalence, proposed etiologic events, and both medical and surgical therapies. In addition, the prognosis for successful outcome and effects on future reproduction will also be described.
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.
Pyometra is a common reproductive disorder which affects nearly one fourth of all female dogs before they reach 10 y of age. An association between pyometra and the most common uterine disease of the bitch, cystic endometrial hyperplasia, has been established, as the latter allows commensal bacteria originating from the vagina to proliferate in the uterus at the end of estrus. The progressive degenerative process in the development of cystic endometrial hyperplasia is usually proposed as the initiating lesion for pyometra in bitches; this is mediated by progesterone and potentially aggravated by estrogens. However, a separate process caused by local uterine irritation to trophoblastic reaction and bacterial proliferation has been recently proposed as an alternate mechanism leading to the development of pyometra. Pyometra is clinically distinct in pathogenesis, signs, treatment and prognosis from postpartum metritis or mucometra. Treatment of pyometra has historically involved ovariohysterectomy, however, during the last 10 y, numerous effective treatments have been proposed to treat both open and closed cervix pyometra with good success and future fertility. Among the treatments available, the use of repeated low doses of prostaglandins alone or in association with either dopamine agonists or progesterone-receptor antagonists has been demonstrated to be a viable alternative for valuable breeding dogs.
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