Iris M Reichler

The effect of GnRH analogs on urinary incontinence after ablation of the ovaries in dogs.

After removal of the ovaries approximately 20% of dogs develop urinary incontinence. Removal of the gonads results in estrogen deficiency and chronic elevation in the production and secretion of FSH and LH. The gonadotrophins may directly or indirectly, adversely affect the sphincter function of the urethra. Estrogen replacement therapy and treatment with sympathomimetics, such as ephedrine or phenylpropanolamine (PPA), are effective only in some of the affected dogs, and many of these subsequently become nonresponsive. Since the role of the elevated gonadotrophins has not been elucidated, we used depot preparations of GnRH analogues to down-regulate gonadotrophins once or twice in 13 ovariectomized (ovx), incontinent dogs, which were either refractory to alpha-adrenergics (n=11) or in which alpha-adrenergics were contraindicated (n=2). Dogs were treated with leuprolide, deslorelin, buserelin or triptorelin. In 7 dogs treatments with GnRH analogues alone (n=11) resulted in continence for 50-738 days (mean 247). In all dogs except one, where GnRH treatments did not resolve the incontinence completely, additional treatment with phenylpropanolamine was successful. With additional treatment of phenylpropanolamine complete continence was restored for 21-367 days (mean 159). All treatments caused long-term reduction of circulating FSH and LH concentrations to very low or undetectable levels. No adverse effects of treatments were observed.

Gonadectomy in cats and dogs: a review of risks and benefits.

The necessity, and in particular the timing, of gonadectomy in dogs and cats is still controversial. This is mainly because gonadectomy confers a mixture of benefits and adverse effects that depend upon the age at neutering, sex, species and breed. In this paper, the long-term risks and benefits of gonadectomy, at various ages, in dogs and cats are reviewed using data describing the effects of desexing on the urogenital tract and on other medical conditions, such as orthopaedic diseases, immune-mediated diseases, tumour development and behaviour.

Prostaglandin E2 functions as a luteotrophic factor in the dog

The luteal phase in dogs is governed by many poorly understood regulatory mechanisms. Functioning of the corpus luteum (CL) is unaffected by hysterectomy. Recently, the role of prostaglandins in regulating canine CL function was addressed suggesting a luteotrophic effect of prostaglandin E2 (PGE2) during the early luteal phase. However, compelling functional evidence was lacking. The potential of PGE2 to stimulate steroidogenesis was tested in canine primary luteal cells isolated from developing CL of non-pregnant dogs. In addition, the luteal expression of prostaglandin transporter (PGT) and steroidogenic acute regulatory protein (STAR) was demonstrated and characterized in CL from non-pregnant bitches during the course of dioestrus as well as from pregnant animals during the pre-implantation, post-implantation and mid-gestation periods of pregnancy and during luteolysis; the luteal expression of PGE2 receptors (EP2 and EP4) has been investigated at the protein level throughout pregnancy. Our findings show that PGE2 is an activator of STAR expression in canine luteal cells from early luteal phase, significantly up-regulating STAR promoter activity and protein expression resulting in increased steroidogenesis. The 3βHSD (HSD3B2) and P450scc (CYP11A1) expression remained unaffected by PGE2 treatment. The expression of PGT was confirmed in CL during both pregnancy and dioestrus and generally localized to the luteal cells. After initial up-regulation during the earlier stages of the CL phase, its expression declined towards the luteal regression. Together with the demonstration of EP2 and EP4 throughout pregnancy, and the decline in EP2 at prepartum, our findings further support our hypothesis that intra-luteal PGE2 may play an important role in regulating progesterone secretion in the canine CL.

Immunohistochemical localization and quantitative assessment of GnRH-, FSH-, and LH-receptor mRNA Expression in canine skin: a powerful tool to study the pathogenesis of side effects after spaying

It has been proposed that gonadotropins and/or gonadotropin releasing hormone (GnRH) could be involved in the pathophysiology of the side effects after spaying in bitches, such as urinary incontinence and an increased production of a woolly undercoat. In order to provide tools to investigate the role of these hormones in dogs we developed immunohistochemical techniques and real-time RT-PCR to study whether GnRH-, LH-, and FSH-receptors exist in canine skin and urinary bladder. Tissue samples from the skin of the flank region and the ventral midline of the urinary bladder from euthanised dogs were examined. We were able to quantify mRNA expression of GnRH-, FSH-, and LH-receptors in canine skin and bladder biopsies with a high primer efficacy. Immunohistochemical studies showed that GnRH-, FSH-, and LH-receptors are expressed in vessel walls, the epidermis, the hair follicle and in sebaceous and sweat glands in canine skin and in transitional epithelium, and smooth muscle tissue in the urinary bladder. Our data provide the fundamentals to examine the distribution of FSH-, LH-, and GnRH-receptors in canine skin and urinary bladder and to assess gene activity at the transcriptional level by real-time RT-PCR.

Ectopic Ureters in Dogs: Clinical Features, Surgical Techniques and Outcome

OBJECTIVE To compare clinical features of ectopic ureter (EU) in male and female dogs and outcome after neoureterostomy with resection restricted to the intravesical part of the ureter for intramural ectopic ureter (iEU) or of ureteroneocystostomy for extramural ectopic ureter (eEU). STUDY DESIGN Retrospective case series. ANIMALS Female dogs (n = 26) with 32 iEU and 8 eEU; male dogs (n = 24) with 25 iEU and 18 eEU. METHODS Data were collected from medical records (1992-2008). Long-term follow-up information after surgical correction by modified neoureterostomy or ureteroneocystostomy was gathered by owner questionnaire. RESULTS Median age at first occurrence of UI was significantly lower in females (<2 months) than in males with EU (8 months; P = 0.0015). Bilateral occurrence and an extramural course of the ureter were more common in males (n = 19 and n = 20, respectively) compared with females (14 and 12, respectively), but the outcome of surgical treatment was comparable in both genders. CONCLUSIONS The prognosis after surgery is fair with a success rate of 72% and a complication rate of 26%. Resection of only the intravesicular ectopic ureter resulted in resolution of incontinence in a high percentage of dogs and thus is an acceptable alternative to removal of the entire ureteral remnant.

Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol

The effects of alfaxalone and propofol on neonatal vitality were studied in 22 bitches and 81 puppies after their use as anesthetic induction agents for emergency cesarean section. After assessment that surgery was indicated, bitches were randomly allocated to receive alfaxalone 1 to 2 mg/kg body weight or propofol 2 to 6 mg/kg body weight for anesthetic induction. Both drugs were administered intravenously to effect to allow endotracheal intubation, and anesthesia was maintained with isoflurane in oxygen. Neonatal vitality was assessed using a modified Apgar score that took into account heart rate, respiratory effort, reflex irritability, motility, and mucous membrane color (maximum score = 10); scores were assigned at 5, 15, and 60 minutes after delivery. Neither the number of puppies delivered nor the proportion of surviving puppies up to 3 months after delivery differed between groups. Anesthetic induction drug and time of scoring were associated with the Apgar score, but delivery time was not. Apgar scores in the alfaxalone group were greater than those in the propofol group at 5, 15, and 60 minutes after delivery; the overall estimated score difference between the groups was 3.3 (confidence interval 95%: 1.6-4.9; P < 0.001). In conclusion, both alfaxalone and propofol can be safely used for induction of anesthesia in bitches undergoing emergency cesarean section. Although puppy survival was similar after the use of these drugs, alfaxalone was associated with better neonatal vitality during the first 60 minutes after delivery.

Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus, pregnancy and normal and induced parturition

BackgroundEndocrine mechanisms governing canine reproductive function remain still obscure. Progesterone (P4) of luteal origin is required for maintenance of pregnancy. Corpora lutea (CL) are gonadotrop-independent during the first third of dioestrus; afterwards prolactin (PRL) is the primary luteotropic factor. Interestingly, the increasing PRL levels are accompanied by decreasing P4 concentrations, thus luteal regression/luteolysis occurs in spite of an increased availability of gonadotropic support. PRL acts through its receptor (PRLr), the expression of which has not yet been thoroughly investigated at the molecular and cellular level in the dog.MethodsThe expression of PRLr was assessed in CL of non-pregnant dogs during the course of dioestrus (days 5, 15, 25, 35, 45, 65 post ovulation; p.o.) as well as in CL, the utero/placental compartments (Ut/Pl) and interplacental free polar zones (interplacental sites) from pregnant dogs during the pre-implantation, post-implantation and mid-gestation period of pregnancy and during the normal and antigestagen-induced luteolysis. Expression of PRLr was tested by Real Time PCR, immunohistochemistry and in situ hybridization.ResultsIn non-pregnant CL the PRLr expression was significantly upregulated at day 15 p.o. and decreased significantly afterwards, towards the end of dioestrus. CL of pregnancy showed elevated PRLr expression until mid gestation while prepartal downregulation was observed. Interestingly, placental but not interplacental expression of PRLr was strongly time-related; a significant upregulation was observed towards mid-gestation. Within the CL PRLr was localized to the luteal cells; in the Ut/Pl it was localized to the fetal trophoblast and epithelial cells of glandular chambers. Moreover, in mid-pregnant animals treated with an antigestagen, both the luteal and placental, but not the uterine PRLr were significantly downregulated.ConclusionsThe data presented suggest that the luteal provision of P4 in both pregnant and non-pregnant dogs may be regulated at the PRLr level. Furthermore, a role of PRL not only in maintaining the canine CL function but also in regulating the placental function is strongly suggested. A possible functional interrelationship between luteal P4 and placental and luteal PRLr expression also with respect to the prepartal luteolysis is implied.

Prediction of Parturition Date in the Bitch and Queen

Assessment of gestational age and parturition date prediction is a challenging, yet common task in clinical management of the pregnant bitch or queen. Knowing the approximate parturition date is essential for a thorough pregnancy monitoring. Radiographic and ultrasonographic methods are suitable in bitches and queens. In the bitch, moreover, ovulation timing by means of LH or progesterone assay, determination of onset of vaginal dioestrus by means of examination of vaginal cytology, and recognition of impending parturition by monitoring prepartal progesterone levels and body temperature variation are practical methods. A combination of different methods increases the accuracy of parturition date prediction.

Spaying-induced coat changes: the role of gonadotropins, GnRH and GnRH treatment on the hair cycle of female dogs

Although spaying can result in qualitative hair coat changes in dogs, the influence of spaying on the hair growth cycle has never been described. The study aims were to examine the effect of spaying and gonadotropin-releasing hormone (GnRH) treatment on canine hair coat, cycle stages of hair follicles, plasma gonadotropin concentrations and mRNA transcription of luteinizing hormone (LH) and GnRH receptors in hair follicles. Fifteen female dogs were examined before and 1 year after spaying and 24 spayed dogs before and after GnRH treatment. Spaying resulted in increased plasma gonadotropin concentrations and increased anagen : telogen ratio of hair follicles, but only 20% of the dogs developed coat changes. No differences were found in mRNA transcription of LH and GnRH receptors. GnRH treatment resulted in reduced plasma gonadotropin concentrations and improvement of coat changes in 79% of patients. This was associated with an increase in catagen hair follicles without changes in the anagen : telogen ratio. The present study demonstrated that spaying had an effect on the anagen : telogen ratio of hair follicles. Spaying-induced coat changes did not correlate with the anagen : telogen ratio. GnRH treatment reduced gonadotropin concentrations and reversed coat changes in some dogs, but had no effect on the hair growth cycle other than increasing the number of catagen hair follicles. A weak positive correlation between the plasma LH concentration and the anagen : telogen ratio was noted; however, our data did not suggest a direct receptor-mediated hormonal effect on the hair follicle. The present study did not identify the pathomechanism of spaying-induced coat changes.

Leptin and leptin receptor gene expression in the canine corpus luteum during diestrus, pregnancy and after aglepristone-induced luteolysis.

Leptin (LEP) and leptin receptor (LEP-R) expression was shown to change throughout the luteal phase in several species and may be involved in steroid hormone production. In the bitch, leptin but not LEP-R protein was detected in the non-pregnant corpus luteum (CL). Until now, no further information has been available on their expression levels and role in CL function. Our objective was to compare time-related changes in luteal LEP and LEP-R mRNA levels during the non-pregnant luteal phase, pregnancy and after aglepristone treatment in mid-gestation. CLs were collected by ovariohysterectomy at different time points: day (d) 5, 15, 25, 35, 45, 65 after ovulation (p.o.) in non-pregnant bitches; pre-implantation, post-implantation, mid-gestation, during prepartum luteolysis; 24 and 72 h after aglepristone injection. Non-pregnant LEP expression was lowest on d5 p.o., increased thereafter and fell again on d45 (P ≤ 0.04). LEP-R expression was not altered (P = 0.07). In pregnant bitches, neither LEP nor LEP-R mRNA levels varied over time (P = 0.201 and P = 0.150, respectively). Aglepristone treatment caused substantial downregulation of luteal LEP expression by 72 h post-treatment (P ≤ 0.01). However, LEP-R expression did not follow the same course (P = 0.193). Our results indicate that both LEP and LEP-R mRNA are present in the canine CL during the non-pregnant luteal phase and pregnancy. LEP expression changes significantly over time in non-pregnant dogs and after aglepristone administration and thus, it may play a role in luteal steroidogenesis and regression.