Mastitis and infertility are the two most common disease complexes in dairy cattle worldwide. Both are multifactorial in nature, are a major reason for culling and have profound negative effects on the profitability of a farm. Mastitis not only affects milk production and milk quality but also is an intensively researched animal welfare issue. Interestingly, a series of epidemiological studies performed in the past decade indicate that mastitis, clinical or subclinical, has negative effects on reproductive performance of dairy cows.
The objective of this paper is to review the current literature and to describe important factors such as type of mastitis (clinical, subclinical), time of occurrence of mastitis relative to artificial insemination (AI), and type of pathogen (gram-positive, gram-negative). Furthermore, the mechanisms by which mastitis can affect reproductive performance were summarized.
Type of mastitis
Mastitis is generally classified as clinical or subclinical depending on the degree of inflammation in the mammary gland. While subclinical mastitis is defined by the elevation of the somatic cell count (SCC) beyond a certain threshold (e.g. 100,000 cells/ml) clinical mastitis is characterized by visible abnormalities of the milk (e.g. watery milk, flakes, clots) and udder (e.g. swelling, hardness of the affected quarter, pain).
Several studies have demonstrated considerable negative effects of clinical mastitis on days to first insemination (up to 22 days more) and days to conception (up to 44 days more). Also clinical mastitis can alter the inter-estrus interval making estrus detection more difficult.
More interestingly an elevation of SCC, typical for subclinical mastitis, around AI is also associated with a significant reduction in the probability of conception. Compared with uninfected cows, newly and chronically infected cows around AI showed reduced conception rates (39.4% vs 32.9% and 31.5%, respectively). Furthermore, around 30% of cows with subclinical chronic mastitis have delayed ovulation, low concentrations of estradiol and a low or delayed pre-ovulatory surge of luteinizing hormone. In one study subclinical mastitis followed by clinical mastitis resulted in the most severe loss in reproductive performance.
Considering the nature of subclinical mastitis (not obvious and only detectable by testing or screening) and the high prevalence (up to 40 %) and the multitude of effects, these relationships require attention both in the field and in research.
Time of occurrence of mastitis relative to artificial insemination
It is well documented that the negative effect of mastitis on fertility varies with the timing of mastitis occurrence and AI. There are, however, inconsistent findings in the literature regarding the most susceptible period. In one study clinical mastitis occurring any time between 14 days before until 35 days after an AI was associated with a lower probability of conception and clinical mastitis occurring 0 to 7 days after AI was associated with the greatest reduction in probability of conception. In another study, reduced conception rates were observed in cows that suffered from clinical mastitis within the three weeks before insemination, but not at other times. An older study based on an extensive data set (i.e. 9,369 lactations) showed that the effects of some diseases on first service conception were strongly dependent on the interval since last disease occurrence. This was especially true for clinical mastitis, which had a small effect on conception when it occurred before AI and a much more pronounced effect (i.e. > 50% reduction in pregnancy risk) when it occurred after AI.
A single high elevation of SCC (> 106 cells/mL on only one milk test day) lowered the probability of conception by 23.6% when it occurred during the 10 days immediately before AI, but not when it occurred earlier. For 30 days after AI, the probability of conception was lowered by about 23%. Cows with clinical mastitis during the first 45 days of gestation were at 2.7 times higher risk of abortion (95% confidence interval: 1.3 to 5.6) within the next 90 days than were cows without mastitis.
Mechanisms by which mastitis can affect reproduction
There are several findings elucidating the mechanisms by which mastitis affects conception or maintenance of pregnancy. Briefly, mastitis-induced release of inflammation mediators such as cytokines, interleukins, and Prostaglandin F2α are involved in lowering fertility. Before breeding, mastitis can disrupt hormonal patterns (depression of estradiol production, delayed surge of luteinizing hormone) and delay ovulation. Around insemination, mastitis may affect oocyte maturation and fertilization. After insemination, mastitis may interfere with corpus luteum formation and regression, progesterone secretion, endometrial functions, and embryonic development.
Observations from experimental studies suggested that infusions of E. coli endotoxin involve a prolonged release of Prostaglandin F2α and subsequent stimulation of uterine smooth muscle contractions and luteolytic effect leading to a decline in the concentrations of progesterone. Interestingly, plasma concentrations of cortisol, a hormone related to stress, was also increased. Further research is warranted to better understand the exact mechanisms that account for mastitis-induced suppression of fertility considering time of occurrence relative to AI.
Types of pathogen
Different types of clinical mastitis (i.e., different pathogens) may have varying effects on reproduction. One classification method for clinical mastitis is by staining the causing pathogens to sort into gram-positive and gram-negative. Clinical signs, severity, and treatment protocols differ for gram-positive and gram-negative mastitis. Older studies did not find any differences between gram-positive and gram-negative clinical mastitis in their effect on reproduction. More recently, however, there is evidence that clinical mastitis caused by gram-negative pathogens was associated with larger decreases in probability of pregnancy compared to gram-positive pathogens. One of the very few prospective, controlled randomized trials investigated the efficacy of the J5 vaccine (i.e. a vaccine against the J5 core antigen of coliform bacteria) on milk production and reproductive performance. The probability of pregnancy was significantly reduced in cows if they had a case of clinical mastitis caused by Escherichia coli (42% pregnant) or Streptococcus spp. (38%) whereas 78% of healthy cows conceived.
More recently, a retrospective analysis based on 23,695 lactations considering the type of mastitis provided additional evidence. In general, clinical mastitis due to gram-negative bacteria had a more detrimental effect on probability of conception than did clinical mastitis caused by gram-positive bacteria or other organisms. The greatest effect was an 80% reduction associated with gram-negative clinical mastitis occurring in the week after AI.
Limitations of the studies
Based on a systematic assessment of 12 studies there is clear evidence that both subclinical and clinical mastitis negatively affect reproductive performance in dairy cows. However, most of these studies were retrospective and data had been collected over long periods of time (e.g. up to 7 or 11 years) without knowledge of a subsequent analysis. It is questionable whether relevant aspects of study design such as disease definitions, diagnostic methods, inclusion criteria, and treatments were handled consistently over such long periods. Plausible changes in management practices and treatment protocols over these periods and their effects were not reported or discussed. Furthermore, in some studies cows were enrolled multiple times thus introducing a certain bias; and in older studies statistical procedures were either inappropriate or were inadequately described.
Therefore more prospective and controlled randomized trials are necessary to provide further solid evidence of the relationship between mastitis and reproductive performance (considering plausible co-factors such as timing, treatment, and milk yield) and to suggest sound preventive measures.
Text: Prof. dr. Wolfgang Heuwieser – firstname.lastname@example.org
Photos: Twan Wiermans
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