First report of vaginal prolapse in a bitch treated with oestrogen

Vaginal prolapse is the protrusion of edematous vaginal tissue into and through the opening of the vulva occurring during the pro-oestrus and oestrus stages of the sexual cycle. True vaginal prolapse may occur near parturition, as the concentration of serum progesterone declines and the concentration of serum oestrogen increases. In a bitch, true vaginal prolapse is a very rare condition. This case report describes an 18-month-old crossbreed bitch, weighing 40 kg presented with type III vaginal prolapse. The patient had developed vaginal prolapse after receiving oestrogen in order to oestrus induction. Subsequent to unsuccessful attempts for repositioning, ovariohysterectomy (OHE), circumferential excision of the prolapsed tissue and finally vulvoplasty were performed. There was no evidence of recurrence of the prolapse during 30 days after surgery. This case report describes type III vaginal prolapse as an unusual side effect of oestrus induction hormonal therapy in the bitch.     

True vaginal prolapse in a bitch

Frequently, vaginal fold prolapse is the protrusion of edematous vaginal tissue into and through the opening of the vulva occurring during proestrus and estrus stages of the sexual cycle. True vaginal prolapse may occur near parturition, as the concentration of serum progesterone declines and the concentration of serum oestrogen increases. In the bitch, this type of true vaginal prolapse is a very rare condition.

This short communication describes a 5-year-old female, cross-breed dog in moderate condition, weighing 33 kg, with distocia and true vaginal prolapse. Abdominal palpation and transabdominal ultrasonography revealed live and dead foetuses in the uterine horns. One dead and four live fetuses were removed from uterus by cesarean section. The ovariohysterectomy was performed after repositioning the vaginal wall with a combination of traction from within the abdomen and external manipulation through the vulva. Re-occurrence of a vaginal prolapse was not observed and the bitch recovered completely after the surgical therapy.

Compared to other vaginal disorders, vaginal prolapse is an uncommon condition in the bitch. In the present case, extreme tenesmus arising from distocia may have predisposed to the vaginal prolapse. The cause of dystocia was probably the disposition of the first foetus. We concluded that the vaginal prolapse was the result of dystocia in the present case.     

Pregnancy, lactation and the oestrous cycle of the pouched mouse, Saccostomus campestris

The anatomy and histology of pouched mouse ovaries were studied during the oestrous cycle, pregnancy and lactation along with the relationship between the ovarian structures and circulating concentrations of progesterone. The structure of the ovaries resembled that of most rodents. Follicular development indicated that ovulation takes place on the night between pro-oestrus and oestrus, i.e. at the time when mating normally occurs. Corpora lutea were accumulating in cyclic females, while successively disappearing during pregnancy, leaving only the set formed after conception. After parturition luteal regression was rapid. Theca interna, included in the corpora lutea, formed glandular stromal tissue after regression of the luteal tissue formed from granulosa cells. The progesterone profile of non-pregnant females indicated a short but functional luteal phase (peak at metoestrus) during the cycle. During pregnancy three peaks of progesterone stood out: (1) when implantation starts, (2) when older sets of corpora lutea showed rejuvenation and placental signs were found in the vaginal smears, and (3) 3 days before expected parturition when luteal development (as judged by histology) reached a peak. The placenta may participate in but not 'take over' the progesterone production during later stages of pregnancy. Very low concentrations of peripheral progesterone during lactation and a very low level of follicular development at that time support an earlier suggestion of a lactational anoestrus in pouched mice.     

Changes in Muscularis Propria of Anterior Vaginal Wall in Women with Pelvic Organ Prolapse

The objective of this study was to evaluate the morphological and immunohistochemical alterations of tissue removed from the upper third of anterior vaginal wall in a sample group of the female population presenting homogenous risk factors associated with pelvic organ prolapse (POP). The case study consisted of 14 patients with POP and there were 10 patients in the control group. Patient selection was carried on the basis of specific criteria and all of the patients involved in the study presented one or more of the recognized POP risk factors. Samples were taken from POP patients during vaginal plastic surgery following colpohysterectomy, and from control patients during closure of the posterior fornix following hysterectomy. Samples were processed for histological and immunohistochemical analyses for Collagen I and Collagen III, α-Smooth Muscle Actin (α-SMA), Platelet-Derived-Growth-Factor (PDGF), matrix metalloproteinase 3 (MMP3), tissue inhibitors metalloproteinase 1 (TIMP1), Caspase3. Immunofluorescence analyses for Collagen I and III and PDGF were also carried out. In prolapsed specimens our results show a disorganization of smooth muscle cells that appeared to have been displaced by an increased collagen III deposition resulting in rearrangement of the muscularis propria architecture. These findings suggest that the increase in the expression of collagen fibers in muscularis could probably be due to a phenotypic switch resulting in the dedifferentiation of smooth muscle cells into myofibroblasts. These alterations could be responsible for the compromising of the dynamic functionality of the pelvic floor.Key words: Pelvic organ prolapse, immunohistochemistry, smooth muscle cells, collagen, PDGF     

Prediction of nonlinear elastic behaviour of vaginal tissue: experimental results and model formulation

The mechanical properties of the vaginal tissue need to be characterised to perform accurate simulations of prolapse and other pelvic disorders that commonly affect women. This is also a fundamental step towards the improvement of therapeutic techniques such as surgery. Issues like the efficiency of using autologous tissue in pelvic reconstruction may be addressed. The goal of this study was to characterise the elastic behaviour of vaginal tissue. For this purpose, prolapsed vaginal tissue from eight different post-menopausal patients, excised during prolapse corrective surgery, was mechanically tested. The mechanical testing of vaginal tissue, consisting of uniaxial tension tests performed along the longitudinal axis of the vagina, revealed the nonlinear mechanical behaviour of the tissue. The material model parameters were fit to the experimental data using the Levenberg–Marquardt optimisation algorithm. All the curve fittings showed a good agreement between experimental and theoretical results, evidenced by R ² values close to 1 and by very low ? values.     

Relationship of vaginal impedance with speed of return to oestrus after weaning, oestrous behaviour, parity and lactation length in cyclic sows

The effect of weaning to oestrus interval, oestrus duration, parity, lactation length, breed and their interactions on changes of vaginal impedance in sows after weaning and during oestrus was examined. The impedance measurements were carried out by a four-electrode method. The interval from weaning to oestrus was significantly longer in sows with the length of lactation 21-25 days than 26-30 days and 31-36 days and in primiparous than multiparous sows. The interval from weaning to oestrus was negatively correlated with the length of lactation (r=-0.21; P<0.05), parity (r=-0.36; P<0.01) and oestrus duration (r=-0.26; P<0.01). The weaning to oestrus interval, oestrus duration, parity and lactation length had a significant effect and the breed of sows had no influence on the vaginal impedance in peri-oestrus. The decrease of vaginal impedance after weaning was delayed in sows with a longer weaning to oestrus interval and in primiparous than multiparous sows. The decline of vaginal impedance during peri-oestrus was more gradual in sows with a longer interval from weaning to oestrus, shorter lactation, primiparous sows and sows with the length of oestrus 36 h and 72 h and more. The nadir of vaginal impedance occurred earlier before oestrus in sows with a shorter oestrus. The interaction of weaning to oestrus interval with parity and oestrus duration and the interaction of oestrus duration with parity significantly affected the vaginal impedance in weaned sows. In conclusion, the weaning to oestrus interval, oestrus duration, parity and lactation length considerably influence the vaginal impedance in sows during peri-oestrus. The findings indicate that the impedance technique may be a useful method for a study of factors and processes that accelerate or slow down the return to oestrus after weaning and affect oestrus duration in sows.     

Effect of sow parity on vaginal electrical impedance

The influence of sow parity on the changes of vaginal impedance after weaning was examined. Sows were monitored twice a day for oestrus via exposure to a sexually mature boar. The criterion for confirmation of ovulation was an increase in plasma progesterone levels above 12.5 nmol l(-1) 8 and 12 days after oestrus onset. The impedance measurements were carried out by a four-terminal method. In sows of all parities, the vaginal impedance decreased gradually after weaning (P < 0.01) and increased during oestrus (P < 0.01). No significant impedance changes were observed thereafter. The vaginal impedance was higher in sows above 6 parities than in sows from parities 1 to 5 from the beginning of oestrus to 14 days after oestrus onset. The impedance was also higher in sows of parity 6 than in sows of parity 1 from the beginning of oestrus to 14 days after oestrus onset and in sows from parities 2 to 5 than in sows of parity 1 from 2 to 4 days after oestrus onset. The difference in average impedance values between sows above 6 parities and sows of parity 1 was two-fold in oestrus compared to the luteal phase. In all measured places of the vagina from the cervix to 6 cm from the cervix, a similar significant increase of impedance was observed during oestrus. The results indicate that the parity of sows affects the electrical impedance of vaginal mucosa measured by means of a four-terminal method.     

Progesterone and oestradiol-17 beta concentration profiles throughout the reproductive cycle in harbour seals (Phoca vitulina)

Serum samples of harbour seals kept in captivity were analysed for progesterone and oestradiol-17 beta. The hormone profiles obtained were used to describe a complete reproductive cycle. A clear peak in oestradiol values, indicative of ovulation, was followed by elevated concentrations of progesterone. Implantation probably occurred 3-3.5 months thereafter. Progesterone concentrations rose significantly in the last 3-4 months of gestation, whereas oestradiol concentrations gradually increased after implantation. Lactational oestrus was marked by a peak of oestradiol on average 25 days after parturition and lactation lasted 4-5 weeks. Previous pregnancy had a marked influence on the timing of oestrus; females with offspring started a new reproductive cycle about 14 days later than previously non-pregnant seals. No differences in timing of parturition between the 2 groups were observed. This was probably the result of a flexible period of delayed implantation.     

Uterine prolapse with an interesting vascular anomaly in a cheetah: a case report

A 5-year-old cheetah suffered a complete prolapse of the left uterine horn after the birth of her second litter. Two attempts to reduce the prolapse transvaginally failed. The animal was hospitalized 13 days after the prolapse first occurred, and an ovariohysterectomy was performed to resolve the prolapse. The prolapsed uterine horn had been mutilated: its tip, together with the ipsilateral ovary was absent. Laparotomy revealed no sign of recent or past hemorrhage or adhesions, or any signs of the left ovarian artery or left ovarian vein in the remnants of the left mesovarium. A large vein crossed the uterine body from the left uterine horn to join the right uterine vein, presumably serving as the only route of venous drainage for the prolapsed uterine horn. A possible cause for the prolapse is excessive mobility of the uterus due to prior rupture of its mesial support. The animal died 24 days after surgery due to chronic renal failure, as a result of severe renal amyloidosis.     

Reproductive cycle of the steppe polecat (Mustela eversmanni)

In laboratory conditions, in a natural photoperiod, testicular redevelopment began in late December. Maximal testis size was attained by the end of February. Testicular regression began in mid-May and was complete by the end of August. Oestrus was first observed in late March and continued throughout April. Females mated for the first time between 30 March and 8 April. Mating generally coincided with peak concentrations of urinary oestrone conjugates and when vaginal lavages contained greater than 90% cornified epithelial cells. Blastocyst implantation occurred by Day 13 and the post-implantation period was 29 days. Gestation ranged from 39 to 43 days and first parturition occurred in mid-May. Concentrations of urinary oestrone conjugates and free progesterone were elevated during the first half of pregnancy, reaching maximum values at mid-pregnancy, and then gradually declined as parturition neared. Litter size of primiparous females averaged 6.8 young/female. Females that were pseudopregnant or lost their litters shortly after birth, and several with weaned kits, exhibited a second oestrus.     

Long-term reversible suppression of oestrus in bitches with nafarelin acetate, a potent LHRH agonist

Adult cyclic beagle bitches were treated for up to 18 months with nafarelin acetate via subcutaneously implanted osmotic pumps, starting during the first week of a pro-oestrous vaginal discharge. The imminent ovulation appeared to be unaffected by treatment, but doses of 8 or 32 micrograms analogue/day reduced the integrated luteal progesterone values. No new oestrus was detected in 3 bitches during 18 months of treatment with 32 micrograms/day, which resulted in mean plasma levels of 0.4 ng analogue/ml. A return to oestrus was observed in all 3 bitches between 3 and 18 weeks after cessation of treatment: 2 of the bitches mated at those times and produced normal litters. Another 2 bitches were similarly treated with 32 micrograms analogue/day; they were mated at the oestrus at start of treatment and dosing was continued for about 63 days. One of the bitches conceived and produced a normal litter. Nafarelin acetate treatment begun during anoestrus resulted in an induced heat 1-2 weeks after the start of treatment. The induced heat consisted of pro-oestrous vaginal discharge, oestrous vaginal cytology, and ovulation (judged by increased circulating levels of progesterone). Three bitches mated at the induced heat and treated for the normal duration of gestation did not litter. Nafarelin treatment of 3 bitches before puberty did not induce signs of oestrus and prevented the occurrence of oestrus through 18 months of treatment. The first oestrus in these bitches occurred 3.5-4 months after cessation of treatment, but mating at that time did not result in pregnancy. These studies have established the feasibility of and dosage requirement for the use of the LHRH agonist as a contraceptive in the bitch.     

Changes of electrical impedance in vaginal vestibule in cyclic sows

The changes of the electrical impedance in the vaginal vestibule during the oestrous cycle and the influence of sow parity on the vestibular impedance in oestrus were examined. Primiparous and multiparous sows of the Large White breed were used. Oestrus was tested via exposure of sows to a sexually mature boar. The criterion for conformation of ovulation was the increase in plasma progesterone levels above 12.5nmoll(-1) on day 8 and 12 after oestrus onset. A two-terminal method was used to measure the impedance. The vestibular impedance rose slightly in the first day after weaning. The impedance increased markedly during oestrus (P<0.01) and decreased during early dioestrus (P<0.01). No significant changes were observed thereafter. The individual sows reached the peak of vestibular impedance between 1 and 3 days after oestrus onset. The parity of sows did not significantly influence the impedance values during oestrus. The study showed that the impedance changes in the vaginal vestibule during peri-oestrus are considerably different from those described earlier in the vagina and that sow parity does not affect the vestibular impedance in oestrus.     

Sequential Hormonal Changes in the Postpartum Dairy Cow

Peripheral plasma levels of 15-keto-13,14-dihydro-PGF2α, progesterone, Cortisol, LH and prolactin were studied in 6 primiparous postpartum dairy cows. The cows were followed by hormone measurements and clinical examinations from parturition until pregnancy was established. Blood was collected 3 times per day. The cervix, uterus and ovaries were examined by rectal palpation at 6–10 days intervals. The cows were observed for signs of oestrus twice daily and were additionally teased with a bull to provoke standing heat. Four cows had a normal parturition and dropped their fetal membranes shortly afterwards. (NR group). The remaining 2 retained their fetal membranes for more than 24 h following parturition (RFM group). One out of 6 cows showed standing oestrus at the first ovulation, 4 animals were in oestrus at the second ovulation and all cows showed signs of oestrus at the third ovulation. Although the length of the first luteal phase varied from 9 to 22 days a corpus luteum was in all cases palpated. The secretion of progesterone during the first luteal phase was terminated by a PGF2α release. A significant difference in 15-keto-13,14-dihydro-PGF2α levels between the 2 groups was found on days 0–4 (2.39 vs 6.87 nmol/1 at Ρ < 0.06). Postpartum prostaglandin F2α release as reflected by the level of 15-keto-13,14-dihydro-PGF2α lasted shorter in the NR group than in the RFM group (15–17 vs 21 days). Significant positive correlations between 15-keto-13,14-dihydro-PGF2α and Cortisol as well as between prolactin and Cortisol during the first 24 days postpartum were noted only in cows having normal parturition. The most pronounced daily prolactin variations occurred during the second luteal phase (NR group), when a significant difference between the times 8.00, 12.00 and 15.00 was recorded (14.7, 31.5 and 19.7 μg/l, respectively). Moreover, a partial negative correlation between log value of prolactin and arithmetical value of LH was found in these cows only during the first luteal phase after parturition.     

Plasma levels of LH, FSH, prolactin, oestradiol-17beta and progesterone during natural and induced oestrus in the dairy goat

The patterns of LH, FSH, prolactin and oestradiol-17beta, before and during natural oestrus, and of progesterone during the following cycle were studied in four French Alpine dairy goats and compared with those obtained after synchronization of oestrus in the same animals. The highest concentration of oestradiol-17beta was measured at the beginning of oestrus and was followed 3 hours later by simultaneous rises of LH, FSH and prolactin. A second FSH peak was observed 48h after the first one. On D(3) (D(0) = day of oestrus) progesterone concentration was over 1 ng/ml. The luteal phase lasted 15 days. Peak concentrations of oestradiol-17beta and progesterone were higher in animals when oestrus was induced. This was attributed to their higher ovulation rate. The second FSH peak was lower, and the interval between oestradiol-17beta peak and gonadotrophin surge longer, than at natural oestrus.     

Regulation of elastolytic proteases in the mouse vagina during pregnancy, parturition, and puerperium

Recent evidence indicates that failure of elastic fiber assembly and synthesis is involved in the pathophysiology of pelvic organ prolapse in mice. It has been long been hypothesized that parturition-induced activation of proteases in the vaginal wall and its supportive tissues may contribute to pelvic organ prolapse in women. In this investigation, we determined the expression of matrix metalloproteases with elastase activity (matrix metalloproteinase [MMP] 2, MMP9, and MMP12) and their inhibitors in the vaginal wall of nonpregnant, pregnant, and postpartum mice. Data obtained using mRNA levels and enzyme activity measurements indicate that MMP2, MMP9, and 21- to 24-kDa caseinolytic serine proteases are regulated in vaginal tissues from pregnant and postpartum mice. Although suppressed during pregnancy and the early postpartum time period, MMP2 and MMP9 enzyme activities are increased after 48 h, a time when mRNA levels of protease inhibitors (tissue inhibitor of MMP2 [Timp2], cystatin C [Cst3], and alpha-1 antitrypsin [Serpina1]) are decreased. We conclude that recovery of the vaginal wall from pregnancy and parturition requires increased elastic fiber assembly and synthesis to counteract the marked increase in elastolytic activity of the postpartum vagina.     

Peripheral plasma levels of oestradiol-17 beta and progesterone in the bitch during the oestrous cycle, in normal pregnancy and after dexamethasone treatment.

Plasma oestradiol-17 beta concentrations in Labradors increased during pro-oestrus to an average maximal concentration of of 79-7 +/- 10-9 (S.D.) pg/ml, and then fell rapidly. In 6/7 bitches the peak occurred within 1 day of oestrus. No consistent changes in plasma oestradiol levels were observed during pregnancy and at parturition and the values were similar to those in late anoestrus. Plasma progesterone levels did not increase markedly during pro-oestrus. At oestrus, progesterone values rose and maximal concentrations, which varied from about 20 to about 55 ng/ml, were reached within a few days of the oestradiol peak. Plasma progesterone decreased in late pregnancy and in one of the three bitches studied in detail low or undetectable levels were reached 10 days before parturition. In the other two bitches an abrupt decrease in progesterone occurred just before parturition. Dexamethasone treatment (2 X 5 mg daily for 10 days) from Day 30 of pregnancy resulted in intrauterine death and resorption of the fetuses in the two bitches studied. Treatment from about Day 45 resulted in the birth of dead fetuses at Days 55 and 59 of pregnancy. The changes in plasma oestradiol levels were very small. No changes in plasma progesterone levels were seen when dexamethasone was given in late pregnancy, but an accelerated decline occurred after treatment in mid-pregnancy.     

Some aspects related to conception of the Japanese monkey (Macaca fuscata)

The season of birth, age of the first parturition, gestation period, and vaginal bleeding and mating after conception were surveyed with Japanese monkeys (Macaca fuscata). The analyses of the former two items were dependent on the birth records in the Ohirayama troop collected from 1957 to 1973, and the analyses of the latter two items were dependent on data obtained by a 48-hour mating in a laboratory. Birth in the Ohirayama troop converged into the months from March to July, especially from April to June. The age of the first parturition was three years and 11 months at the earliest, and nine years and two months at the latest. The monkeys giving their first birth at the age of five or thereabouts were most frequently observed (68.6%), and most of the monkeys had their first parturition from about the age of four years to about the age of six years. The gestation period calculated from 17 cases, which was defined as the period from the first day of a 48-hour mating to the day before parturition, was 173 ± 6.9 days ranging from 161 to 188 days. In 25 out of 28 cases, the vaginal bleeding was observed after conception. It began slightly later (between 16 and 24 days after mating) than the forecasted time of the next menstrual hemorrhage, and usually lasted longer than bleeding of the usual menses. Each of three female monkeys caged together with a male monkey 30 days after conception was observed to have copulated, and the male was observed to have ejaculated.     

Effect of thyroid hormone on initiation of persistent oestrus in the rat.

When rats are exposed to continuous illumination persistent oestrus and polyfollicular ovaries develop. Thyroidectomy at 24 days of age (juvenile rats) prevents the onset of persistent oestrus and polyfollicular ovaries under exposure to constant light, and irregular ovulation continues to occur. Replacement with 1.75 microng L-thyroxine in these rats produces a prolonged oestrus. However, in adult persistent-oestrous rats (90 days after exposure to continous illumination) thyroidectomy does not interrupt persistent vaginal cornification. In rats receiving 100 microng of testosterone propionate subcutaneously at 5 days of age, persistent oestrus and polyfollicular ovaries develop. Thyroidectomy at 24 days of age (juvenile) prevents the onset of persistent oestrus and the development of polyfollicular ovaries, however, ovulation is not observed. Replacement treatment with 1.75 microng L-thyroxine in these rats produces a prolonged oestrus and polyfollicular ovaries. However, in adult persistent oestrus rats, thyroidectomy at 130 days does not interrup persistent vaginal cornification. From these facts, it may be inferred that circulation of a physiological level of thyroid hormone in juvenile rats is necessary for the development of oestrogen binding receptors in the hypothalamus. Therefore, a hypothyroid state during the juvenile stage interferes with the development and maturation of hypothalamic controlled pituitary ovarian function.     

Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse

Matrix metalloprotease (MMP) activity is increased in the postpartum vagina of wild-type (WT) animals. This degradative activity is also accompanied by a burst in elastic fiber synthesis and assembly. The mechanisms that precipitate these changes are unclear. The goals of this study were to determine how vaginal distention (such as in parturition) affects elastic fiber homeostasis in the vaginal wall and the potential significance of these changes in the pathogenesis of pelvic organ prolapse. Vaginal distention with a balloon simulating parturition resulted in increased MMP-2 and MMP-9 activity in the vaginal wall of nonpregnant and pregnant animals. This was accompanied by visible fragmented and disrupted elastic fibers in the vaginal wall. In nonpregnant animals, the abundant amounts of tropoelastin and fibulin-5 in the vagina were not increased further by distention. In contrast, in pregnant animals, the suppressed levels of both proteins were increased 3-fold after vaginal distention. Distention performed in fibulin-5-deficient (Fbln5(-/-)) mice with defective elastic fiber synthesis and assembly induced accelerated pelvic organ prolapse, which never recovered. We conclude that, in pregnant mice, vaginal distention results in increased protease activity in the vaginal wall but also increased synthesis of proteins important for elastic fiber assembly. Distention may thereby contribute to the burst of elastic fiber synthesis in the postpartum vagina. The finding that distention results in accelerated pelvic organ prolapse in Fbln5(-/-) animals, but not in WT, indicates that elastic fiber synthesis is crucial for recovery of the vaginal wall from distention-induced increases in vaginal protease activity.