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A. Rowson, DVM and D. Kirk, Ph.D., PAS
Phibro Animal Health Corporation, Quincy, IL

Impaired reproductive performance of dairy cows can have significant impact on the profitability of dairy operations.  The immune system has been shown to play a role in dairy cow reproduction, both indirectly, through the effects of mastitis, metritis, retained placenta, and metabolic diseases; and directly, through actions of immune cells upon the ovary.  A properly-functioning immune system may help improve reproductive performance of dairy cattle by reducing occurrence of diseases affecting fertility, and improving immune cell activity.


The cow’s estrous cycle is approximately 21 days long.  It is divided into two phases which are characterized by changes on the ovary.  The follicular phase makes up 20% of the cycle.  During this phase the pre-ovulatory follicle on the ovary, which contains the oocyte (or egg), produces estrogen.  When estrogen concentrations are high enough, a surge of luteinizing hormone (LH) is released, initiating ovulation. The luteal phase begins after ovulation, when the follicle transforms into a corpus luteum (CL) which produces progesterone to maintain pregnancy.  This phase makes up the remaining 80% of the estrous cycle.


Reproductive performance is monitored using several metrics:
Calving Interval   Period between calvings
Days Open   Period between calving and confirmed conception
Services Per Conception   Total services per total number of pregnant cows
Heat Detection Rate   Percent of eligible cows that are bred
Conception Rate   Percent of cows bred that are pregnant
Pregnancy Rate   Percent of cows eligible to become pregnant that are confirmed pregnant during a given period (usually 21 days)


Reproductive performance is affected by both breeding success and pregnancy loss. Typically, gestation lasts 280 days. Up to 40% of pregnancies are lost in first 17 days of gestation. Early embryonic loss occurs from 0 to 15 days of gestation, and is usually not detected since pregnancy loss at this stage does not delay estrus. Late embryonic loss occurs at 16 to 41 days of gestation, and will delay ovulation and thus extend the estrous cycle. Embryonic losses usually occur before pregnancy is confirmed. Abortion occurs between 42 to 260 days of gestation, and stillbirths occur from 260 days of gestation through birth. “Normal” abortion rates are 3% to 5% per year.


Mastitis is associated with: increased Days Open1,2; greater Services/Conception2; reduced Conception Rate3,1; reduced Pregnancy Rate4,1; higher incidence of Early Embryonic Death5,6; and greater risk of abortion7,1. Infection of the udder affects the structure and function of the ovaries8 and has also been associated with altered patterns of reproductive hormone secretion4. These effects may be linked to a systemic response by cytokines9 (molecules released by cells that affect actions of other cells, particularly immune cells) which may also lead to pregnancy loss10.

Retained placenta can also have indirect effects upon fertility, including: reduced Conception Rate3; lower Pregnancy Rate11; more Services per Conception12; and increased Days Open13. Retained placenta is associated with reduced neutrophil function and lower blood concentrations of interleukin-814 (IL-8, a cytokine that attracts immune cells to sites of infection), and may alter activities of the CL15.

Uterine disease, which includes metritis (inflammation of the entire uterus) and endometritis (inflammation of the uterine lining), is associated with: lower Conception Rate16; reduced Pregnancy Rate11; and increased Days Open17. Uterine disease appears to have the greatest impact on fertility by reducing ovulation rate18 and CL size19 during the first post-partum estrous cycle. Cows with uterine disease also have smaller follicles and lower blood estrogen concentrations20. Cows that develop uterine disease experience reduced neutrophil function around the time of calving21,22.

Metabolic diseases are also associated with impaired reproductive performance.

  • Milk fever increases Days to 1st Service11
  • Subclinical hypocalcemia reduces 1st Service Conception Rate23
  • Ketosis increases Days to 1st Service & decreases 1st Service Conception Rate11
  • Mastitis combined with other diseases has greater negative impact on reproduction than any one disease alone24

Immune cells, primarily neutrophils, macrophages, and T-lymphocytes, are required by the ovary for normal ovulation and CL function25. Activities of these immune cells are regulated by the luteal environment, and result in both CL development and regression26. Neutrophils migrate into the early CL (day 1 to 4 of the estrous cycle), in response to IL-8 produced by the CL. Neutrophil numbers and IL-8 concentrations are low at the mid- and late-luteal phase but IL-8 is high at luteal regression. Interestingly, cortisol (a potent, immunosuppressive hormone released in response to stress) acts to block the release and peak of LH from the pituitary gland, which can prevent ovulation.

The immune system has both direct and indirect effects upon reproduction in dairy cows. Reproductive performance may be improved with a properly-functioning immune system.

1Santos, J. E. P., R. L. A. Cerri, M. A. Ballou, G. E. Higginbotham, J. H. Kirk. 2004. Effect of timing of first clinical mastitis occurrence on lactational and reproductive performance of Holstein dairy cows. Animal Reproduction Science 80:31–45.

2Schrick, F. N., M. E. Hockett, A. M. Saxton, M. J. Lewis, H. H. Dowlen, and S. P. Oliver. 2001. Influence of subclinical mastitis during early lactation on reproductive parameters. J. Dairy Sci. 84:1407–1412.

3Hertl, J. A., Y. T. Gröhn, J. D. G. Leach, D. Bar, G. J. Bennett, R. N. González, B. J. Rauch,
F. L. Welcome, L. W. Tauer, and Y. H. Schukken. 2010. Effects of clinical mastitis caused by gram-positive and gram-negative bacteria and other organisms on the probability of conception in New York State Holstein dairy cows. J. Dairy Sci. 93:1551–1560.

4Hockett, M. E., R. A. Almeida, N. R. Rohrbach, S. P. Oliver, H. H. Dowlen, and F. N. Schrick. 2005. Effects of Induced Clinical Mastitis During Preovulation on Endocrine and Follicular Function. J. Dairy Sci. 88:2422–2431.

5Chebel, R. C., J. E. P. Santos, J. P. Reynolds, R. L. A. Cerri, S. O. Juchem, and M. Overton. 2004. Factors affecting con- ception rate after artificial insemination and pregnancy loss in lactating dairy cows. Anim. Reprod. Sci. 84:239.

6Moore, D. A., M. W. Overton, R. C. Chebel, M. L. Truscott, and R. H. BonDurant. 2005. Evaluation of factors that affect embryonic loss in dairy cattle. J. Am. Vet. Med. Assoc. 226:1112.

7Risco, C. A., G. A. Donovan, and J. Hernandez. 1999. Clinical mastitis associated with abortion in dairy cows. J Dairy Sci. 82:1684–1689.

8Rahman, M. M., M. Mazzilli, G. Pennarossa, T. A. L. Brevini, A. Zecconi, and F. Gandolfi. 2012. Chronic mastitis is associated with altered ovarian follicle development in dairy cattle. J. Dairy Sci. 95:1885–1893.

9Chebel, R. C. 2007. Mastitis effects on reproduction. NMC Regional Meeting Proc. (2007):43–55.

10Soto, P., R.P. Natzke, and P.J. Hansen. 2003. Identification of possible mediators of embryonic mortality cause by mastitis: actions of lipopolysaccharide, prostaglandin F2α, and the nitric oxide generator, sodium
nitroprusside dihydrate, on oocyte maturation and embryonic development in cattle. Am. J. Reprod. Immunol. 50:263.

11Fourichon, C., H Seegers, and X. Malher. 2000. Effect of disease on reproduction in the dairy cow: a meta-analysis. Theriogenology 53:1729–1759.

12Joosten, I., J. Stelwagen, A. A. Dijkhuizen. 1988. Economic and reproductive consequences of retained placenta in dairy cattle. Veterinary Record 123, 53–57.

13Yeon-Kyung, H and K. Ill-Hwa. 2005. Risk factors for retained placenta and the effect of retained placenta on the occurrence of postpartum diseases and subsequent reproductive performance in dairy cows. J. Vet. Sci. 6(1), 53–59.

14Kimura, K., J. P. Goff, M. E. Kehrli, Jr. and T. A. Reinhardt. 2002. Decreased Neutrophil Function as a Cause of Retained Placenta in Dairy Cattle. J. Dairy Sci. 85:544–550.

15Holt, L. C., W. D. Whittier, F. C. Gwazdaukas, and W. E. Vinson. 1989. Early Postpartum Reproductive Profiles in Holstein Cows with Retained Placenta and Uterine Discharges. J. Dairy Sci. 72:533–539.

16Dubuc, J., T. F. Duffield, K. E. Leslie, J. S. Walton, and S. J. LeBlanc. 2011. Effects of postpartum uterine diseases on milk production and culling in dairy cows. J. Dairy Sci. 94:1339–1346.

17Giuliodori, M. J., R. P. Magnasco, D. Becu-Villalobos, I. M. Lacau-Mengido, C. A. Risco, and R. L. de la Sota. 2013. Metritis in dairy cows: Risk factors and reproductive performance. J. Dairy Sci. 96:3621–3631.

18Herath, S., H. Dobson, C. E. Bryant, and I. M. Sheldon. 2006. Use of the cow as a large animal model of uterine infection and immunity. Journal of Reproductive Immunology 69 (2006) 13–22.

19Strüve, K., K. Herzog, F. Magata, M. Piechotta, K. Shirasuna, A. Miyamoto and H. Bollwein. 2013. The effect of metritis on luteal function in dairy cows. BMC Veterinary Research 9:244–252.

20Sheldon, I. M., E. J. Williams, A. N. A. Miller, D. M. Nash, S. Herath. 2008. Uterine diseases in cattle after parturition. The Veterinary Journal 176:115–121.

21Cai, T. Q., P. G. Weston, L. A. Lund, B. Brodie, D. J. McKenna, and W. C. Wagner. 1994. Association between neutrophil functions and periparturient disorders in cows. Am. J. Vet. Res. 55:934–943.

22Hammon, D. S., I. M. Evjen, T. R. Dhiman, J. P. Goff, and J. L. Walters. 2006. Neutrophil function and energy status in Holstein cows with uterine health disorders. Vet. Immunol. Immunopath. 113:21–29.

23Chapinal, N., M. E. Carson, S. J. LeBlanc, K. E. Leslie, S. Godden, M. Capel, J. E. P. Santos, M. W. Overton, and T. F. Duffield. 2012. The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance. J. Dairy Sci. 95:1301–1309.

24Ahmadzadeh, A., M. A. McGuire, J. C. Dalton. 2010. Interaction between Clinical Mastitis, Other Diseases and Reproductive Performance in Dairy Cows. WCDS Advances in Dairy Technology Volume 22:83–95.

25Walusimbi, S. S., and J. L. Pate. 2013. Physiology and Endocrinology Symposium: Role of immune cells in the corpus luteum. J. Animal Sci., 91:1650-1659.

26Jiemtaweeboon, S., K. Shirasuna, A. Nitta, A. Kobayashi, H. J. Schuberth, T. Shimizu and A. Miyamoto. 2011. Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow. Reproductive Biology and Endocrinology 9:79–88.


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