Causes for pre-implantation embryo loss, which can be as high as 50% or more of fertilized embryos, are multifactorial and largely undescribed. Studies in cattle using mastitis as a model indicate that one cause of early embryonic loss is infectious disease or activation of immune responses at sites outside the reproductive tract. Infection of the mammary gland in dairy cattle is associated with a reduction in pregnancy rate (proportion of inseminated cows that become pregnant) and an increase in the number of inseminations required to establish pregnancy. Also, intravenous challenge with bacterial peptidoglycan and polysaccharide at approximately days 3-5 after breeding reduced subsequent pregnancy rate in sheep that had been previously immunized against the same material. The mechanism by which extrauterine activation of immune and inflammatory responses leads to embryonic loss is not clear although cytokines probably play a crucial role. Effects could be exerted at the level of the hypothalamic-pituitary axis, ovary, reproductive tract or embryo. Interferon (IFN)-alpha, for example, which can reduce pregnancy rate in cattle when injected around 13-19 days after breeding, increases body temperature, inhibits secretion of luteinizing hormone, and reduces circulating concentrations of progesterone. Other cytokines or products of cytokine activation could cause embryonic loss by causing hyperthermia (as elevated temperature blocks oocyte function and embryonic development), exerting toxic effects on the corpus luteum [for example, IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and prostaglandin F(2alpha)], stimulating endometrial prostaglandin synthesis [TNF-alpha and interleukin(IL)-1beta], reducing endometrial cell proliferation (IL-1beta), and interfering with oocyte maturation and embryonic development (TNF-alpha, nitric oxide, and prostaglandin F(2alpha)). Although largely neglected by reproductive immunologists, study of the involvement of the immune system in pre-implantation embryonic loss is likely to lead to new methods for enhancing fertility.

Results indicate that increased local concentrations of LPS, PGF2alpha, and NO can have deleterious consequences on oocyte function (LPS, PGF2alpha) and embryonic development (NO). Thus, these molecules are putative mediators of effects of infectious disease or inflammation, including mastitis, on fertility of cattle.

TNF-alpha can have deleterious actions on oocyte maturation that compromise development of the resultant embryo. While exposure of fertilized embryos to TNF-alpha did not inhibit development to the blastocyst stage, TNF-alpha increased the percentage of blastomeres undergoing apoptosis when exposure occurred for embryos > or = 9-cells. Increased blastomere apoptosis could conceivably compromise subsequent embryo survival.

During summer, 34 cows received daily injections of placebo or 25 mg of bST and were placed in a thermoregulated or a heat stress environment. Heat stress increased rectal temperatures, respiration rates, and plasma cortisol concentrations and decreased milk yield. Four of 9 bST-treated cows and none of 8 control cows became atactic on the 1st d of heat stress. When exposed to heat stress, cows treated with bST experienced higher rectal temperatures throughout the trials than cows treated with placebo. Nonetheless, bST increased milk yields in both environments. The major effect of heat stress on immune function was decreased migration of leukocytes to the mammary gland after chemotactic challenge. This effect of heat stress was not altered by bST. In summary, hyperthermia induced by heat stress and associated changes were greater for cows treated with bST. Detected effects of heat stress on the immune system were few and were not alleviated by bST. Use of bST during summer in subtropical climate zones requires careful management to avoid overexposure of bST-treated cows to heat stress.

Two methods of drying off cows, intermittent milking and abrupt cessation, were studied with data from 9254 quarters of cows on 36 New York dairy farms. Eighty percent of the cows were infused with nine different antibiotic preparations separately at drying off, and 20% served as controls. Cows dried off by intermittent milking has a similar number of quarters infected at drying off, had fewer spontaneous recoveries, had a higher rate of cure, and developed fewer new infections in control quarters in comparison with cows dried off by the stop method. Methods worked equally well in treated cows. However, intermittent milking resulted in fewer infections at subsequent calving than stop milking in nondry treated cows. Cows producing less than or equal to 4 kg of milk at drying off were more highly infected than higher producing cows. Hind quarters contained more infections at drying off, fewer responded to therapy, and more infections developed in the dry period. Cows with dry periods of less than or equal to 30 days had more infected quarters respond to therapy and had the fewest new infections in the dry period. The role of routine dry cow therapy in decreasing the number of infections in dairy herds by preventing new infections and removing old infections is demonstrated.