The effect of intrauterine administration of estradiol on postpartum uterine involution in cattle

In cattle, the first postpartum dominant follicle has a predilection for the ovary contralateral to the previously gravid uterine horn. However, the presence of an estradiol-secreting dominant follicle in the ipsilateral ovary is a marker of subsequent fertility, possibly due to a localized effect of ovarian estradiol on uterine involution. The present study tested the hypothesis that estradiol increases the rate of uterine involution when administered into the previously gravid uterine horn around the expected time of selection of the first postpartum dominant follicle. Dairy cows were treated with 10 mg estradiol benzoate (n=15) or saline (n=14) administered through the cervix into the previously gravid uterine horn lumen on Days 7 and 10 postpartum. Uterine involution was monitored by daily transrectal ultrasonography and estimation of peripheral plasma concentrations of PGFM and acute phase proteins, while ovarian function was monitored by ultrasonography and measurement of plasma hormone concentrations. There was no effect of estradiol treatment on the diameter of the previously gravid or nongravid uterine horns, nor on the plasma concentrations of PGFM or acute phase proteins. However, cows in which the first postpartum dominant follicle ovulated during the study period had a smaller diameter of the previously gravid (P<0.01) or nongravid uterine horns (P<0.001) compared with cows in which the follicle regressed. Thus, our hypothesis was not proven, and the opposite pathway of utero-ovarian signaling may be more important during the postpartum period.     

Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle

Bacteria contaminate the uterus of most dairy cattle after parturition and endometritis causes infertility. An endometritis score can be ascribed based on the vaginal mucus character and odour but it is not clear if the clinical score reflects the number of uterine bacteria or the inflammatory response. The present study tested the hypothesis that clinical evaluation of endometritis reflects the number of bacteria present in the uterus, and the acute phase protein response. Swabs (n = 328) were collected from the uterine lumen of dairy cattle, 21 and 28 days postpartum, vaginal mucus was scored for character and odour, and blood samples collected for acute phase protein measurement. Bacteria were identified following aerobic and anaerobic culture, and the bacterial growth density was scored semi-quantitatively. When bacteria were categorised by their expected pathogenic potential in the uterus, purulent or fetid odour vaginal mucus was associated with the growth density of pathogenic bacteria but not opportunist contaminants. When bacteria were analysed independently, Arcanobacterium pyogenes, Proteus and Fusobacterium necrophorum growth densities were associated with mucopurulent or purulent vaginal mucus. The bacterial growth densities for A. pyogenes, Escherichia coli, non-hemolytic Streptococci, and Mannheimia haemolytica were associated with a fetid mucus odour. Peripheral plasma concentrations of alpha(1)-acid glycoprotein were higher if there was a fetid compared with a normal vaginal mucus odour (1.50 +/- 0.09 mg/mL versus 1.05 +/- 0.02 mg/mL, P < 0.001), but did not differ significantly between vaginal mucus character scores. The evaluation of the character and odour of vaginal mucus reflects the number of bacteria in the uterus, and the acute phase protein response.     

The effect of oestradiol on postpartum uterine involution in sheep

The present study tested the hypothesis that ovarian oestradiol increases the rate of uterine involution after parturition in sheep. The day after parturition, ewes were randomly assigned as un-operated controls (n=5), or a 3 cm silastic implant containing oestradiol (n=8) or empty (n=7) was sutured within the bursa of the ovary ipsilateral to the previously gravid uterine horn. Blood samples were collected daily for measurement of PGFM and acute phase proteins until 17 days postpartum when the ewes were slaughtered and the genital tract was collected. There was no consistent effect of treatment group on uterine involution determined by the collagen density, dry matter content, width, length, or weight of the genital tract. Furthermore, there was no evidence of a localised effect of oestradiol on involution as there were no significant differences between the previously gravid and non-gravid uterine horns. However, oestradiol-treated ewes had lower plasma concentrations of 15-keto-13,14-dihydro-prostaglandin F2alpha (P<0.01), alpha1-acid glycoprotein (P<0.05) and ceruloplasmin (P<0.001); but, not haptoglobin. These observations could reflect a direct effect of oestradiol on inflammatory mediator synthesis or secretion because, in the absence of parallel physical measurements, it is unlikely that these observations reflect a beneficial effect of treatment on uterine health.     

Defining postpartum uterine disease in cattle

Uterine function is often compromised in cattle by bacterial contamination of the uterine lumen after parturition, and pathogenic bacteria often persist, causing uterine disease, a key cause of infertility in cattle. However, the definition or characterization of uterine disease frequently lacks precision or varies among research groups. The aim of the present paper was to provide clear clinical definitions of uterine disease that researchers could adopt. Puerperal metritis should be defined as an animal with an abnormally enlarged uterus and a fetid watery red-brown uterine discharge, associated with signs of systemic illness (decreased milk yield, dullness or other signs of toxemia) and fever > 39.5 degrees C, within 21 days after parturition. Animals that are not systemically ill, but have an abnormally enlarged uterus and a purulent uterine discharge detectable in the vagina, within 21 days post partum, may be classified as having clinical metritis. Clinical endometritis is characterised by the presence of purulent (> 50% pus) uterine discharge detectable in the vagina 21 days or more after parturition, or mucuopurulent (approximately 50% pus, 50% mucus) discharge detectable in the vagina after 26 days post partum. In the absence of clinical endometritis, a cow with subclinical endometritis is defined by > 18% neutrophils in uterine cytology samples collected 21-33 days post partum, or > 10% neutrophils at 34-47 days. Pyometra is defined as the accumulation of purulent material within the uterine lumen in the presence of a persistent corpus luteum and a closed cervix. In conclusion, we have suggested definitions for common postpartum uterine diseases, which can be readily adopted by researchers and veterinarians.     

Bacterial complications of postpartum uterine involution in cattle

The bacterial contamination of the postpartum uterus is a frequent finding which by itself does not disturb the anatomical and histological restoration of tubular genital tract. The improper balance between uterine infection and the intrauterine antimicrobial self-defence mechanisms, however, often results in complications, such as puerperal metritis, clinical endometritis, pyometra and subclinical endometritis. After reviewing the bacteriology of uterine involution, and the predisposing factors for its bacterial complications, this paper defines the different clinical forms, and summarizes their pathology, furthermore, the recent progress in diagnostic considerations and principles of current treatments for these diseases of bovine genitals.     

Postpartum uterine infection in cattle

Postpartum uterine infections results from uterine contamination with bacteria during parturition. The prevalence of uterine infections varies considerably among studies. Uterine infection implies adherence of pathogenic organisms to the mucosa, colonization or penetration of the epithelium, and/or release of bacterial toxins that lead to establishment of uterine disease. The development of uterine disease depends on the immune response of the cow, as well as the species and number (load or challenge) of bacteria. The postpartum uterus has a disrupted surface epithelium in contact with fluid and tissue debris that can support bacterial growth. A variety of species of bacteria, both Gram-positive and Gram-negative aerobes and anaerobes, can be isolated from the early postpartum uterus. Most of these are environmental contaminants that are gradually eliminated during the first 6 weeks postpartum. A normal postpartum cow resolves uterine infection by rapid involution of the uterus and cervix, discharge of uterine content, and mobilization of natural host defenses, including mucus, antibodies and phagocytic cells. Clinical signs of uterine infection vary with the virulence of the causative organisms and the presence of factors that predispose to the disease. The treatment of endometritis and metritis in bovine should be directed towards improving fertility. The antibiotic should be active against the main uterine pathogens and should maintain its activity in the environment of the uterus. Also, should not inhibit the normal defense mechanisms and should be well tolerated and not induce irritation in the endometrium. Effective use of hormones in uterine infection requires knowledge of both normal reproductive endocrinology and the therapeutic characteristics of available hormonal preparations.     

Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection

Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and that the constitutively elevated uterine NO during pregnancy may help contain or even reduce the risk of infection-related complications.     

Effect of subclinical uterine infection on cervical and uterine involution, estrous activity and fertility in postpartum buffaloes

Nili-Ravi buffaloes (n=29) that calved normally between August and November and did not develop any clinical reproductive disorder after calving were studied for the incidence of sub-clinical bacterial infection of the uterus and its effects on postpartum reproductive efficiency. The incidence of subclinical uterine infection was 24% (7/29). Involution of the cervix and uterus was slower (P < 0.01) in the infected group than in the normal group (45.6 vs 31.1 days and 46.3 vs 35.8 days), respectively. The mean diameters of cervix and gravid horn on Day 12 post partum and on completion of involution did not differ between buffaloes of the two groups. However, the rate of involution of the cervix and the gravid horn was lower in buffaloes of the infected group (2.2 vs. 2.7 mm/day and 2.6 vs. 3.2 mm/day). The mean interval to first post partum ovulation was similar in buffaloes in the infected (35.5 days) and the normal group (33.8 days). The life span of corpus luteum formed after first ovulation was shorter (11 days) in buffaloes of both groups than that of a normal estrous cycle (15 to 17 days). The incidence of silent ovulation was apparently higher in buffaloes of the infected group (83 vs. 60%) but the difference was not significant. For the first four months after calving, the mean interval to first postpartum estrus was longer in buffaloes of the infected group (73.0 vs. 47.7 days; P < 0.01). Similarly, the average service period was longer in buffaloes of the infected group (91.0 vs. 64.8 days; P < 0.05). The overall pregnancy rate for the first four months after calving did not differ between buffaloes of the two groups. We conclude that subclinical bacterial infection of the postpartum uterus delays the cervical and uterine involution which can, in turn, delay the occurrence of first postpartum estrus and prolong the service period in buffaloes.     

Effect of vehicle on intrauterine absorption of gentamicin in cattle

An intrauterine (IU) infusion of 4 ml gentamicin solution (G) was administered in a water vehicle to 4 normal cycling and healthy cows and in a saline vehicle to 4 other cows during the diestrous phase (days 7–14) of the cycle. Infusion solution (IS) and blood samples were collected periodically postinfusion. G concentration was determined in plasma and IS by radioimmunoassay. Eighty-three and 18% of the infused G disappeared from the uterine lumen by 6 hours postinfusion on using water and saline vehicles, respectively.Total amounts of G reaching the blood stream were nearly the same during the 6 hours postinfusion period using water and saline vehicles. This suggested the possibility of retention of drug in uterine tissue using the distilled water vehicle.     

Effect of administration of eCG to postpartum cows on folliculogenesis in the ovary ipsilateral to the previously gravid uterine horn and uterine involution

This study tested the hypothesis that increased oestradiol secretion by large follicles in the ovary ipsilateral to the previously gravid uterine horn has a local effect to increase the rate of uterine involution. Cows were administered an i.m. water placebo (n = 19), 250 iu equine chorionic gonadotrophin (eCG) (n = 18) or 750 iu eCG (n = 20) 14 days post partum (day 0). Transrectal ultrasonography at the time of treatment and 2, 4 and 6 days later monitored uterine horn diameter and ovarian structures. Blood samples collected contemporaneously were assayed for 15-keto-13, 14-dihydro-prostaglandin F(2alpha) and oestradiol concentration. For control cows, accumulated diameter of the largest follicle in the ovary ipsilateral to the previously gravid uterine horn, compared with the contralateral ovary, was smaller on day 0 (P < 0.05) and days 2, 4 and 6 (P < 0.001). There were no significant differences in the eCG-treated animals. There were 12, 8 and 11 cows with a plasma oestradiol concentration < 1 pg ml(-1) on day 0 in the control, 250 and 750 iu eCG treatment groups, respectively. For control cows, the peripheral oestradiol concentrations were higher on day 6 compared with days 0, 2 and 4 (P < 0.05); for cows treated with 250 iu eCG, concentrations were higher on days 4 and 6 compared with day 0 (P < 0.05); and for cows treated with 750 iu eCG, concentrations were higher on days 2 and 4 compared with day 0 (P < 0.01). Treatment with eCG, or the presence of a follicle > 8 mm in diameter in the ovary ipsilateral to the previously gravid uterine horn, did not affect the rate of uterine involution or plasma 15-keto-13,14-dihydro-prostaglandin F(2alpha) concentration. In conclusion, administration of eCG to increase follicular growth and oestradiol production overcame the inhibition of follicular growth in the ovary ipsilateral to the previously gravid uterine horn, but did not affect uterine involution.     

Influence of intrauterine infections and follicular development on the response to GnRH administration in postpartum dairy cows

The effects of intrauterine infections and prior follicular development on the response to gonadotropin releasing hormone (GnRH) administration in postpartum dairy cows were studied. Fifty lactating Holstein cows were assigned at random to one of two groups after calving. Group I (control) consisted of 25 cows given a single intramuscular injection of saline on Day 15 postpartum. Group II (treated) consisted of 25 herdmates given a single i.m. injection of 100 mug of GnRH on Day 15 postpartum. Palpation per rectum and real-time ultrasonography were used to monitor ovarian activity, and endometrial swabs were cultured to determine the presence of uterine infection. Blood samples were collected for progesterone (P(4)) and luteinizing hormone (LH) analysis. Fourteen cows (control, n = 5; treated, n = 9) did not ovulate during the first 60 d postpartum. Ovaries in these cows contained 4 to 8-mm size follicles and both P(4) and LH remained at basal concentrations. Fourteen other cows (control, n = 6; treated, n = 8) ovulated by Day 15 postpartum. Follicles >/= 10 mm were demonstrable in the ovaries of these cows before or by Day 12 postpartum. GnRH treatment had no effect on the lifespan of the existing corpus luteum in these cows. In the remaining cows, 7 of 14 Control and all 8 Treated cows ovulated within 3 d of treatment. All cows ovulating within this period were free of uterine infection and the ovaries contained follicles 相似文献   

Steroidal regulation of uterine resistance to bacterial infection in livestock

Postpartum uterine infections reduce reproductive efficiency and have significant animal welfare and economic consequences. Postpartum uterine infections are classified as nonspecific, but Arcanobacterium pyogenes and Escherichia coli are usually associated with them in cattle and sheep. Pyometra is the most common type of uterine infection in dairy cattle, and it is detected almost exclusively in cows with active corpora lutea. Luteal progesterone typically down-regulates uterine immune functions and prevents the uterus from resisting infections. Progesterone also can down-regulate uterine eicosanoid synthesis. This seems to be a critical event in the onset of uterine infections, because eicosanoids can up-regulate immune cell functions in vitro. In addition, exogenous prostaglandin F2 alpha stimulates uterine secretion of prostaglandin F2 alpha and enhances immune functions in vivo. Thus, one may hypothesize that eicosanoids can override the negative effects of progesterone and that the up-regulatory effects of exogenous prostaglandin F2 alpha allow the uterus to resolve an infection, regardless of progesterone concentrations. Based on the results of studies to test that hypothesis, cows, sheep, and pigs in various physiological statuses are resistant to intrauterine infusions of Arcanobacterium pyogenes and Escherichia coli, unless progesterone concentrations are increased. In sheep and pigs, exogenous prostaglandin F2 alpha stimulates uterine production of prostaglandin F2 alpha and allows the uterus to resolve Arcanobacterium pyogenes-Escherichia coli-induced infections, even when progesterone is maintained at luteal phase concentrations before and after treatment. Prostaglandin F2 alpha is a proinflammatory molecule that stimulates the production of various proinflammatory cytokines, and it may enhance uterine production of leukotriene B₄. Proinflammatory cytokines and leukotriene B₄ enhance phagocytosis and lymphocyte functions. Even though there are clear associations among prostaglandin F2 alpha, leukotriene B4, proinflammatory cytokines, phagocytosis, and lymphocyte functions, the mechanism of action of exogenous prostaglandin F2 alpha in overriding the down-regulatory effects of progesterone and resolving uterine infections has not been elucidated. Defining this mechanism should yield new prevention and treatment strategies for uterine infections that do not rely on antibiotic and antimicrobial compounds.     

Effect of sometribove administration on LH concentration in dairy cattle

Sixteen lactating, normally cycling Holstein cows were used to study 1) the effects of sometribove (recombinant methionyl bST) administration on basal LH concentrations and 2) the pituitary response to a GnRH challenge during the breeding period. The cows received a 3-injection regimen of PGF2a for estrus synchronization between 40 and 50 d post partum, and were assigned to a control group or to sometribove treatment (25 mg/d), which began 54 to 59 d post partum. Duration of the bST treatment was 24 d. On Day 10 of the estrous cycle following the third PGF2a injection, blood samples were collected to determine basal concentrations of LH. Immediately following this collection period, a GnRH challenge (100 mug) was used to measure the responsiveness of the pituitary based on the subsequent LH peak. Milk production of sometribove-treated cows increased 7% (2.1 kg/d) above that of the controls. Sometribove did not affect basal or GnRH-induced LH concentrations. Plasma progesterone concentrations during the luteal phase were similar between treatments. Sometribove increased milk yield with no apparent effects on basal or GnRH-induced LH concentrations during the breeding period.     

Effect of postpartum intrauterine treatment with 2% polyvinyl-pyrrolidone-iodine solution on reproductive efficiency in cows

The effect of a routine postpartum intrauterine infusion of 50 to 100 ml 2 % polyvinylpyrrolidone (PVP) -iodine solution on the reproductive performance of dairy cows was investigated in field trials. At a regular herd visit, alternate cows (n = 531) at around one month after calving (maximum 50 and minimum 20) were treated in utero with PVP-iodine. Additional cows (n = 474) were left untreated or were infused in utero with physiological saline and served as controls. The first service conception rate, overall conception rate within 180 d after calving, and average interval in days from parturition to conception were 48.5 and 74.5 %, 98 ± 36 d in the treated group and 54.9 and 75.9 %, 90 ± 34 d in the controls. Thus, the routine postpartum treatment with 2 % PVP-iodine solution was not effective in improving the reproductive efficiency of cows. The results were nearly the same in all groups, across herd, year of trial, parity, interval from parturition to treatment and dose of PVP-iodine solution. Besides, for cows with endometritis, an intrauterine infusion of PVP-iodine solution was not only ineffective but it was detrimental to fertility.     

Protection of mice against bacterial infection by oral administration of bacterial lipopolysaccharide

The effect of orally administered bacterial lipopolysaccharide (LPS) on host resistance against bacterial infections was studied. LPS orally given for 5 consecutive days prior to infection caused no apparent toxic effect and protected mice against Pseudomonas aeruginosa and Listeria monocytogenes infections.     

Effect of intrauterine devices on uterine structure in goats. 3. Myometrial characteristics

This study investigated quantitative changes in myometrial characteristics that occur in the presence of IUDs in the ovariectomized goat uteri with and without exogenous ovarian steroid administration. The IUD alone reduced myometrial thickness and hormones increased the myometrium. IUDs significantly increased the thickness of the circular layer, while longitudinal muscle was reduced in the presence of the IUD. Both IUD and estrogen increased nuclear count per unit area in the circular muscle when acting separately and reduced the nuclear count when acting together.