Animal Reproduction (AR)
Animal Reproduction (AR)
Congress Paper

Inflammation: friend or foe of bovine reproduction?

Sylvie Chastant, Marie Saint-Dizier

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Inflammation is not only the first line of defense of the organism but is also required in many reproductive processes such as ovulation, corpus luteum development, luteolysis, uterine clearance after insemination and post partum. Nevertheless, if excessive or persistent, inflammation can switch from a positive mechanism to a deleterious process, impairing oocyte quality and embryo development. Not only uterine but also non genital inflammatory sites can depreciate reproductive performances, with a carry over effect of 2 to 4 months. Since the metabolic challenges of the peripartum transition period make difficult for the cow to control inflammation, dairy cows are frequently in a pro-inflammatory stage, suggesting that inflammation, rather than infection, is a limiting factor of fertility in modern dairy cows. Within the first week after calving, cows have to mount an intense inflammatory response to the bacterial invasion of the uterine cavity with the challenge of being able to switch it off in no more than 5-6 weeks. The absence of neutrophils on endometrial smear is associated with the highest success rate at insemination. Since a fine tuning – rather than an absence - of inflammation is required along the reproductive cycle, anti-inflammatory drugs do not allow any improvement of pregnancy rate, except in the specific case of embryo transfer. Appropriate management of the transition period (especially nutritional) and in a long term perspective, genetic selection contribute to improve the aptitude of cows to controls the intensity of inflammatory process.


inflammation; ovulation; post partum; cytokines; neutrophils.


Aguiar TS, Araujo CV, Tirloni RR, Martins LR. 2013. Effect of meloxicam on pregnancy rate of recipient heifers following transfer of in vitro produced embryos. Reprod Domest Anim, 48:984-988.

Albaaj A, Foucras G, Raboisson D. 2017. High somatic cell counts and changes in milk fat and protein contents around insemination are negatively associated with conception in dairy cows. Theriogenology, 88:18-27.

Banerjee J, Sharma R, Agarwal A, Maitra D, Diamond MP, Abu-Soud HM. 2012. IL-6 and mouse oocyte spindle. PLoS One, 7(4):e35535.

Baravalle ME, Stassi AF, Velazquez MML, Belotti EM, Rodriguez FM, Ortega HH, Salvetti NR. 2015. Altered expression of proinflammatoru cytokines in ovarian follicles of cows with cystic ovarian disease. J Comp Pathol, 153:116-130.

Beagley JC, Whitman KJ, Baptiste KE, Scherzer J. 2010. Physiology and Treatment of Retained Fetal Membranes in Cattle. J Vet Intern Med, 24:261-268.

Bogado Pascottini O, Hostens M, Sys P, Vercauteren P, Opsomer G. 2016. Cytological endometritis at artificial insemination in dairy cows: Prevalence and effect on pregnancy outcome. J Dairy Sci, 100:588-597.

Britt JH. 1992. Impacts of early postpartum metabolism on follicular development and fertility. The Bovine Proceedings, 24:39-43.

Bromfield JJ, Sheldon IM. 2011. Lipopolysaccharide initiates inflammation in bovine granulosa cells via the TLR4 pathway and perturbs oocyte meiotic progression in vitro. Endocrinology, 152(12):5029-40.

Broom LJ, Kogut MH. 2018. Inflammation: friend or foe for animal production? Poult Sci, 97:510-514.

Cheong SH, Sa Filho OG, Absalon-Medina VA, Schneider A. Butler WR, Gilbert RO. 2017. Uterine and systemic inflammation influences ovarian and follicular function in postpartum dairy cows. PLos One, 12(5): e0177356.

Dadarwal D, Palmer C, Griebel P. 2017. Mucosal immunity of the postpartum bovine genital tract. Theriogenology ,104:62-71.

Danesh Mesgaran S, Gartner MA, Wagener K, Drillich M, Ehling-Schulz M, Einspanier R, Gabler C. 2018. Different inflammatory responses of bovine oviductal epithelial cells in vitro to bacterial species with distinct pathogenicity characteristics and passage number. Theriogenology, 106:237-246.

Davies CJ, Fisher PJ, Schlafer DH. 2000. Temporal and regional regulation of major histocompatibility complex class I expression at the bovine uterine/placental interface. Placenta, 21:194-202.

Deguillaume L. 2010. L’inflammation génitale post partum de la vache. PhD dissertation. AgroParisTech, Paris, France.

Diskin MG, Parr MH, Morris DG. 2011. Embryo death in cattle: an update. Reprod Fertil Dev, 24:244-251.

Drillich M, Tesfaye D, Rings F, Schellander K, Heuwieser W, Hoelker M. 2012. Effects of polymorphonuclear neutrophil infiltration into the endometrial environment on embryonic development in superovulated cows. Theriogenology, 77:570-578.

Duffy DM, Ko CM, Jo M, Brannstrom M, Curry Jr TE. 2019. Ovulation: parallels with inflammatory processes. Endocr Rev, 40:369-416.

Espey LL. 1980. Ovulation as an inflammatory reaction - a hypothesis. Biol Reprod, 22:73-106

Freeman SL, Green MJ, England GCW. 2013. Uterine fluid from bitches with mating-induced endometritis reduces the attachment of spermatozoa to the uterine epithelium. Vet J, 198:76-80.

Gilbert RO, Santos NR. 2016. Dynamics of postpartum endometrial cytology and bacteriology and their relationship to fertility in dairy cows. Theriogenology, 85:1367-74.

Gilbert RO. 2019. Mechanisms of disruption of fertility by infectious diseases of the reproductive tract. J Dairy Sci, 102:3754-3765.

Ginther OJ, Beg MA. 2012. The hour of transition into luteolysis in horses and cattle: A species comparison. Theriogenology, 77:1731-1740.

Hawk HW. 1987. Transport and fate of spermatozoa after insemination of cattle. J Dairy Sci, 70:1487-1503.

Heiser A, LeBlanc SJ, McDougall S. 2018. Pegbovigrastim treatment affects gene expression in neutrophils of pasture-fed, periparturient cows. J Dairy Sci, 101:1-14.

Herath S, Williams EJ, Lilly ST, Gilbert RO, Dobson H, Bryant CE, Sheldon IM. 2007. Ovarian follicular cells have innate immune capabilities that modulate their endocrine function. Reproduction, 134:683-693.

Herath S, Lilly ST, Santos NR, Gilbert RO, Goetze L, Bryant CE, White JO, Cronin J, Sheldon IM. 2009. Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reprod Biol Endocrinol, 7:55.

Heuwieser W, Iwersen M, Goetze L. 2011. Efficacy of carprofen on conception rates in lactating dairy cows after subcutaneous or intrauterine administration at the time of breeding. J Dairy Sci, 94:146-151.

Heuwieser, W, Grunert, E. 1987. Significance of chemotactic activity for placental expulsion in cattle. Theriogenology, 27: 907- 912.

Hill J, Gilbert R. 2008. Reduced quality of bovine embryos cultured in media conditioned by exposure to an inflamed endometrium. Aust Vet J, 86:312-316.

Huang Y, Chuan H, Haifeng Y, Ruichen L, Xinxin F, Xiaoyan L, Jian H, Weiyun C, Yuehui Z. 2019. Inflamm-Aging: a new mechanism affecting premature ovarian insufficiency. J Immunol Res, 1-7.

Jiemtaweeboon S, Shirasuna K, Nitta A, Kobayashi A, Schuberth HJ, Shimizu T, Miyamoto A. 2011. Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow. Reprod Biol Endocrinol, 9:79.

Katila T. 2012. Post mating inflammatory responses of the uterus. Reprod Domest Anim, 47(Suppl 5), 31-41.

Kaufmann TB, Drillich M, Tenhagen BA, Forderung D, Heuwieser W. 2009. Prevalence of bovine subclinical endometritis 4h after insemination and its effects on first service conception rate. Theriogenology, 71:385-91.

Kimura K, Goff JP, Kehrli ME, Reinhardt TA. 2002. Decreased neutrophil function as a cause of retained placenta in dairy cattle. J Dairy Sci, 85: 544- 550.

König S, May K. 2019. Phenotyping strategies and quantitative-genetic background of resistance, tolerance and resilience associated traits in dairy cattle. Animal, 13:897-908.

Korzekwa A, Murakami S, Wocławek-Potocka I, Bah MM, Okuda K, Skarzynski DJ. 2008. The influence of TNFalpha on the secretory function of bovine corpus luteum; TNF and its receptor expression during the estrous cycle. Reprod Biol, 8:245-262.

Kvidera SK, Horst EA, Abuajamieh M, Mayorga EJ, Fernandez MV, Baumgard LH. 2017. Glucose requirements of an activated immune system in lactating Holstein cows. J Dairy Sci, 100(3):2360-2374.

Lavon Y, Ezra E, Leitner G, Wolfenson D. 2011. Association of conception rate with pattern and level of somatic cell count elevation relative to time of insemination in dairy cows. J Dairy Sci, 94:4538-4535.

LeBlanc SJ. 2012. Interactions of Metabolism, Inflammation, and Reproductive Tract Health in the Postpartum Period in Dairy Cattle. Reprod Domest Anim, 47:18-30.

LeBlanc SJ. 2014. Reproductive tract inflammatory disease in postpartum dairy cows. Animal, 8(s1):54-63

Ling T, Hernandez-Jover M, Sordillo LM, Abuelo A. 2018. Maternal late-gestation metabolic stress is associated with changes in immune and metabolic responses of dairy calves. J Dairy Sci, 101:6568-6580.

Loeffler SH, de Vries MJ, Schukken YH. 1999. The effects of time of disease occurrence, milk yield, and body condition on fertility of dairy cows. J Dairy Sci, 82:2589-2604.

Lucy MC, Evans TJ, Pock SE. 2016. Lymphocytic foci in the endometrium of pregnant dairy cows: characterization and association with reduced placental weight and embryonic loss. Theriogenology, 86:1711-1719.

Machado Pfeifer LF, de Souza Andrade J, Moreira EM, Reis da Silva R, Araújo Neves PM, Moreira da Silva G, Lemos IC, Schneider A. 2018 Uterine inflammation and fertility of beef cows subjected to timed AI at different days post partum. Anim Reprod Sci,197:268-277.

Maj JG, Kankofer M. 1997. Activity of 72kDa and 92kDa matrix metalloproteinases in placental tissues of cows with and without retained fetal membranes. Placenta, 18: 683- 687.

Marey MA, Yousef MS, Kowsar R, Hambruch N. 2016. Local immune system in oviduct physiology and pathophysiology: attack or tolerance? Domest Anim Endocrinol, 56:S205-S211.

McDougall S, Abbeloos E, Piepers S, Rao AS, Astiz S, Van Verwen T, Statham J, Perez-Villalobos N. 2016. Addition of meloxicam to the treatment of clinical mastitis improves subsequent reproductive performance. J Dairy Sci, 99:1-17.

Mitchell JR, Senger PL, Rosenberger JL. 1985. Distribution and retention of spermatozoa with acrosomal and nuclear abnormalities in the cow genital tract. J Anim Sci, 61:956-967.

Miyamoto A, Shirasuna A, Hayashi KG, Kamada D, Kawashima C, Kaneko E, Acosta T, Matsui M. 2006. Potential use of color ultrasound as a tool for reproductive management: new observations using color ultrasound scanning that were not possible with imaging only in black and white. J Reprod Dev, 52:153-160.

Miyamoto A, Shirasuna K, Wijayagunawardane MP, Watanabe S, Hayashi M, Yamamoto D, Matsui M, Acosta TJ. 2005. Blood flow: a key regulatory component of corpus luteum function in the cow. Domest Anim Endocrinol, 29:329-39.

Murdoch WJ, Colgin DC, Ellis JA. 1997. Role of Tumor Necrosis Factor-alpha in the ovulatory mechanism of ewes. J Anim Sci, 75:1601-5.

Nelli RK, De Koster J, Roberts JN, De Souza J, Lock AL, Raphael W, Agnew D, Contreras GA. 2019. Impact of uterine macrophage phenotype on placental retention in dairy cows. Theriogenology, 127:145e152.

Neuvians TP, Schams D, Berisha B, Pfaffl MW. 2004. Involvement of proinflammatory cytokines, mediators of inflammation and basic Fibroblast Growth Factor in prostaglandin F2alpha - induced luteolysis in bovine corpus luteum. Biol Reprod, 70:473-480.

Perrin L, Bostelmann RW, Sheldon IM. 2007. Reduced conception rates associated with bovine mastitis during a «window of opportunity». Vet Rec,161:61-62.

Piersanti RL, Horlock AD, Block J, Santos JEP, Sheldon IM, Bromfield JJ. 2019 Persistent effects on bovine granulosa cell transcriptome after resolution of uterine disease. Reproduction, pii: REP-19-0037.R1.

Price JC, Sheldon IM. 2013. Granulosa cells from emerged antral follicles of the bovine ovary initiate inflammation in response to bacterial pathogen-associated molecular patterns via Toll-like receptor pathways. Biol Reprod, 89(5):119.

Pugliesi G, Khan F.A., Hannan M.A., Beg M.A., Carvalho G.R., Ginther OJ. 2012. Inhibition of prostaglandin biosynthesis during postluteolysis and effects on CL regression, prolactin, and ovulation in heifers. Theriogenology, 78: 443-454.

Ribeiro ES, Carvalho MR. 2017. Impact and mechanisms of inflammatory diseases on embryonic development and fertility in cattle. Anim Reprod, 14:589-600.

Ribeiro ES, Gomes G Greco LF, Cerri RLA, Vieira-Neto A, Monteiro PLJ Jr, Lima FS, Bisinotto RS, Thatcher WW, Santos JEP. 2016. Carryover effect of postpartum inflammatory diseases on developmental biology and fertility in lactating dairy cows. J Dairy Sci, 99:2201-2220.

Ruiz R, Tedeschi LO, Sepúlveda A. 2017. Investigation of the effect of pegbovigrastim on some periparturient immune disorders and performance in Mexican dairy herds. J Dairy Sci, 100:1-13.

Scenna FN, Hockett ME, Towns TM, Saxton AM, Rohrbach NR, Wehrman ME, Schrick FN. 2005. Influence of a prostaglandin synthesis inhibitor administered at embryo transfer on pregnancy rates of recipient cows. Prostaglandins Other Lipid Mediat, 8:38-45

Sheldon IM, Cronin JG, Bromfield JJ. 2019. Tolerance and innate immunity shape the development of postpartum uterine disease and the impact of endometritis in dairy cattle. Annu Rev Anim Biosci, 7:361-384.

Sheldon IM, Cronin JG, Pospiech M, Turner ML. 2018. Mechansisms linking metabolic stress with innate immunity in the endometrium. J Dairy Sci 101:3655-3664.

Sheldon IM, Lewis GS, LeBlanc S. Gilbert RO. 2006. Defining post-partum uterine disease in cattle. Theriogenology, 65:1516-1530.

Sheldon IM, Owens SE, Turner ML. 2017. Innate immunity and the sensing of infection, damage and danger in the female genital tract. J Reprod Immunol 119:67-73.

Shirasuna K, Jiemtaweeboon S, Raddatz S, Nitta A, Schuberth HJ, Bollwein H, Shimizu T, Miyamoto A. 2012a. Rapid accumulation of polymorphonuclear neutrophils in the corpus luteum during prostaglandin F2alpha-induced luteolysis in the cow. PlosOne, 7: e29054.

Shirasuna K, Nitta A, Sineenard J, Shimizu T, Bollwein H, Miyamoto A. 2012b. Vascular and immune regulation of corpus luteum development, maintenance and regression in the cow. Domest Anim Endocrinol, 43:198-211.

Silva Silveira PA, Butler WR, LaCount SE, Overton TR, Castilho Barros C, Schneider A. 2019. Polymorphisms in the anti-oxidant paraoxonase-1 (PON1) gene associated with fertility of post partum dairy cows. Theriogenology, 125:302-309.

Stassi AF, Baravalle ME, Belotti EM, Rey F, Gareis NC, Díaz PU, Rodríguez FM, Leiva CJ, Ortega HH, Salvetti NR. 2017. Altered expression of cytokines IL-1alpha, IL-6, IL-8 and TNFalpha in bovine follicular persistence. Theriogenology, 97:104-112.

Thompson-Crispi KA, Hine B, Quinton M, Miglior F, Mallard BA. 2012. Short communication: association of disease incidence and adaptive immune response in Holstein dairy cows. J Dairy Sci, 95:3888-3893.

Turner ML, Cronin JG, Healey GD, Sheldon IM. 2014. Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1, and TLR6. Endocrinology, 155(4):1453-65.

Walter I, Boos A. 2001. Matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitor-2 of matrix metalloproteinases (TIMP-2) in the placenta and interplacental uterine wall in normal cows and in cattle with retention of fetal membranes. Placenta, 22(5):473-83.

Yousef MS, Abd-Elhafeez HH, Talukder AK, Miyamoto A. 2019. Ovulatory follicular fluid induces sperm phagocytosis by neutrophils, but oviductal fluid around oestrus suppresses its inflammatory effect in the buffalo oviduct in vitro. Mol Reprod Dev, 86(7):835-846.

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