Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis
S. CasaroJ.G. PrimT. D. GonzalezFederico CunhaA.C.M. SilvaHerbert YuR.S. BisinottoR.C. ChebelJ.E.P. SantosCorwin D. NelsonSoo Jin JeonR.C. BicalhoJohn P. DriverKlibs N. Galvão
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Keywords:
Metabolome
Metritis
Endometritis
Dysbiosis
The aim of research was to investigate the frequency of metritis and endometritis, also the efficacy of ozone spray treatment in Holstein cows. The cows (n = 91) ranged from 2 to 7 years of age and were housed in two commercial dairy farms in the north-western region of Croatia. The study was conducted over the course of 1 year. The cows were divided into the three groups based on uterine findings and diagnosis (metritis, endometritis and control). The first group comprised cows suffering from metritis diagnosed on days 5 and/or 15 following parturition. The second group included cows diagnosed with endometritis on days 25 and/or 45 after parturition. The third group included animals without clinical signs of uterine in flammation. In cases when metritis or endometritis was established, ozone foam (Riger spray G) was inserted into the uterus. Ozone was applied by means of a vial containing ozonated foam under pressure for 5 seconds. The time to the first postpartal insemination was shorter for controls compared to the metritis and endometritis groups (P<0.05). The days open until pregnancy was the longest (133 days) in cows with endometritis (n = 28). In the control group (n = 41) the days open until pregnancy was 125 days and in the group of cows treated for metritis (n = 22) was 120 days. Conception rates for the first, second and third groups were 1.86, 2.21 and 1.90, respectively. The intrauterine ozone flush therefore has potential to alleviate metritis and endometritis as an effi cacious and cost-effective treatment option with an overall positive effect on fertility and the host regarding tissues in Holstein cows.
Metritis
Endometritis
Vaginal discharge
Ceftiofur
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Since a few decades, dairy cows have shown a steep increase in milk production, which is unfortunately accompanied by a dramatic decline in reproductive performance. In these high yielding cows there are more puerperal problems than in low yielding cows, such as retained placenta, acute metritis and abnormal vaginal discharge. Cows affected by retained placenta and/or acute metritis are furthermore at a significantly higher risk of other typical 'dairy cow diseases' as acetonaemia, left displaced abomasum and cystic ovarian disease.
Therefore it is important that puerperal metritis is treated properly with broadspectrum antibiotics both parenterally and intra-uterine during 1 - 3 days depending on the severity of the symptoms. Cows with chronic endometritis need no treatment before 30 days post partum. From day 30 on they should be treated twice with prostaglandins at an interval of 14 days.
A challenge for the future is to clearly determine all risk factors for uterine disease. One of the major risk factors is a retained placenta. Correct nutrition during the dry off period and a normal calving process under hygienic conditions are the paramount factors in the prevention of this risk factor.
Metritis
Endometritis
Retained placenta
Milk fever
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Since a few decades, dairy cows have shown a steep increase in milk production, which is unfortunately accompanied by a dramatic decline in reproductive performance. In these high yielding cows there are more puerperal problems than in low yielding cows, such as retained placenta, acute metritis and abnormal vaginal discharge. Cows affected by retained placenta and/or acute metritis are furthermore at a significantly higher risk of other typical ‘dairy cow diseases’ as acetonaemia, left displaced abomasum and cystic ovarian disease. Therefore it is important that puerperal metritis is treated properly with broadspectrum antibiotics both parenterally and intra-uterine during 1 – 3 days depending on the severity of the symptoms. Cows with chronic endometritis need no treatment before 30 days post partum. From day 30 on they should be treated twice with prostaglandins at an interval of 14 days. A challenge for the future is to clearly determine all risk factors for uterine disease. One of the major risk factors is a retained placenta. Correct nutrition during the dry off period and a normal calving process under hygienic conditions are the paramount factors in the prevention of this risk factor.
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Reproduction is one of the key pillars of production in many herds and individual animals. In female animals, reproduction can be affected by uterine diseases including metritis and endometritis. The objective of this review is to understand metritis and endometritis, diagnosis and treatment approaches, and the economic impact of uterine inflammations. Metritis is inflammation of the wall of the uterus, whereas endometritis is inflammation of the functional lining of the uterus, called the endometrium. Clinically, they are characterized by an enlarged uterus containing a watery red-brown fluid to viscous off-white purulent uterine discharge, which often has a fetid odor within 10 to 14-days after postpartum period in clinical metritis whereas clinical endometritis can also be observed its clinical signs after 21-days postpartum period. The risk factors for the occurrence of clinical metritis and endometritis include extrinsic factors include calving season and nutrition whereas intrinsic factors include retained fetal membrane (RFM), dystocia, metabolic disturbance, negative energy balance (NEB) and other non-specific diseases. These factors disturbing the normal physiology and weaken the immune system of dairy cattle. The factors favor the multiplication of pathogenic bacteria and cause inflammation of the uterus and results in metritis and endometritis. This result in increased conception interval increase the number of inseminations, loss of milk and meat production, marked drop in fertility and increase the cost of treatment. Clinical metritis and endometritis can be diagnosed by clinical symptoms and cytological examinations. Clinical metritis and endometritis can be treated by anti-inflammatory drugs flunixin meglumine, antibiotics (pens-trip and long-acting oxytetracycline), intrauterine infusion by using saline or iodine tincture solutions. Clinical metritis and endometritis are the most frequent uterine disorders in dairy cows causing decreased fertility leading to high economic losses. Therefore, management of these production diseases can be achieved by early diagnosis and treatment, supplementation of balanced feed containing minerals, vitamins, appropriate proteins and carbohydrates, good quality management during and after calving of the female animals.
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Endometritis
Metritis
Ceftiofur
Puerperal Infection
Cephradine
Retained placenta
Cefalexin
Cervicitis
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Uterine diseases in dairy cows can be classified as puerperal metritis, clinical metritis, clinical endometritis, and subclinical endometritis. These diseases are highly prevalent (affect between 20 and 30% of dairy cows) in high producing dairy cows and have been associated with decreased pregnancy per artificial insemination (AI), extended interval to pregnancy, increased culling, and economic losses. Puerperal metritis is characterized by the presence of an abnormally enlarged uterus, a fetid watery red-brownish uterine discharge associated with signs of systemic illness, and fever (>39.5 o C) within 21 days in milk (DIM). Animals without systemic signs but with an enlarged uterus and a fetid uterine discharge within 21 DIM may be classified as having clinical metritis. Clinical endometritis is characterized by the presence of purulent (>50%) uterine discharge after 21 DIM or mucopurulent (50% pus, 50% mucus) after 26 DIM. In the absence of clinical endometritis, subclinical endometritis is defined by the presence of >18% neutrophils (PMN) in uterine cytology samples collected between 21 and 33 DIM or >10% PMN between 34 and 47 DIM. The main risk factors are dystocia, twins, retained placenta, stillbirth, abortion, prolapsed uterus, and ketosis. Metritis can be successfully treated either by systemic or intrauterine antibiotic treatment. Ceftiofur hydrochloride (Excenel ® ) intramuscularly or ceftiofur crystalline-free acid (Excede ® ) subcutaneously are effective in treating metritis, and oxytetracycline intrauterine is effective in abrogating the negative effects of metritis on milk yield and fertility. Intrauterine administration of cephapirin benzathine (Metricure ® ) is an effective treatment for clinical and subclinical endometritis, although not approved in the United States. Administration of PGF2α does not seem effective for the treatment of clinical or subclinical endometritis.
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Retained placenta
Pyometra
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Metritis and endometritis are the very common postpartum uterine infections that results into infertility in dairy cattle, production loss and economical losses to the farmer. As postpartum uterus favors bacterial growth so it is frequently found in almost of unhygienic environment reared animals. Breaching of birth canal during dystocia, retention of placenta, wet environment during winter season and immunosuppression due to many reasons are the risk factors for the bacteria invasion to uterus. Although in normal condition these infections are eliminated in animals by uterine involution, passage of lochia, and through the mobilization of immune defense system within few weeks after parturition. Bacterial products causes inflammation, suppress pituitary LH secretion, and postpartum ovarian follicular growth and function, which disrupts ovulation, makes cattle infertile and can cause some severe systemic illness, even death of animal. Metritis and endometritis generally treated with the systemic antibiotics. As many study suggested that there is not so significant beneficial effect of intrauterine antibiotic infusions but not to be negated as some found positive effect. Neomycin is only labeled drug for intrauterine preparations. Ceftiofur and oxytetracycline parentally are good choice for the treatment of metritis and endometritis. Thus, metritis and endometritis affected animal having lower conception rates, increased intervals from calving to first service or conception.
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Retained placenta
Cervicitis
Vaginal discharge
Pelvic inflammatory disease
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In a decreasing order, the main three disorders that result in an increased percentage of dairy cow culling are hoof diseases, clinical mastitis and the puerperal pathologies of the genital sphere. The latter are mostly represented by placenta retention, acute or chronic cervicitis, toxic acute metritis, clinical metritis, clinical and subclinical endometritis. The repeat breeding syndrome is a difficult problem for practitioners because endometritis are one of the causes of this syndrome. Often, cows suffering from endometrial inflammation may have clinical signs and sometimes do not. It cannot be a key to success in endometritis diagnosis, but by bringing in better monitoring of the puerperium, and applying certain managerial and diagnostic measures, we can achieve satisfying reproductive results in close correlation with nutrition and climatic factors.
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Metritis
Cervicitis
Culling
Subclinical infection
Retained placenta
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