Gebärmuttererkrankungen des Rindes: mikrobiologische, molekularbiologische und immunologische Aspekte

Widmung

Wir widmen diesen Artikel Herrn Univ.-Prof. Dr. Wolfgang Heuwieser zum 65. Geburtstag.

Zusammenfassung

Postpartale Gebärmutterentzündungen treten beim Rind in unterschiedlichen Ausprägungen als puerperale Metritis oder klinische Endometritis auf und können über 40 % der Kühe einer Herde betreffen. Unabhängig von ihrem klinischen Erscheinungsbild zählen sie zu den häufigsten Ursachen für Fruchtbarkeitsstörungen bei Rindern und verursachen erhebliche Einbußen in der Produktivität der Milchkühe und letztendlich in der Wirtschaftlichkeit der Betriebe. Obwohl Erkrankungen der Gebärmutter schon seit vielen Jahren Gegenstand der wissenschaftlichen Diskussion sind, fehlen weiterhin, trotz entsprechender Versuche zur Vereinheitlichung, einheitliche Definitionen der verschiedenen Ausprägungen uteriner Erkrankungen. Durch Anwendung neuer technischer Entwicklungen und Testverfahren konnte ein immenser Fortschritt hinsichtlich der Kenntnisse über physiologische Zusammenhänge und pathologische Mechanismen erreicht werden. Bovine (Endo)metritiden können als multifaktorielle Erkrankungen angesehen werden und resultieren aus dem Zusammenspiel einer mikrobiellen Infektion, einer Dysregulation des Immunsystems und einwirkenden Risikofaktoren. Dieses Zusammenspiel wird auf den Ebenen der Mikrobiologie und Molekularbiologie und auch mithilfe der Bioinformatik und Molekulargenetik intensiv erforscht. Im Ergebnis wurden unter anderem neue Bakterienspezies beschrieben, die zur Entstehung der Erkrankung beitragen können, Effekte von Entzündungsmediatoren erklärt sowie metabolische und genetische Einflüsse und Zusammenhänge zu nachfolgenden Fruchtbarkeitsstörungen beschrieben. Daraus ergeben sich nicht nur Grundlagen für mögliche neue Therapie- und Präventionsansätze, sondern auch Ansätze, die in der tierärztlichen Praxis heute schon genutzt werden können. Dieser Artikel soll eine Übersicht über den aktuellen Stand der Forschung zur bovinen Metritis und Endometritis mit einem Schwerpunkt auf mikrobiologischen, molekularbiologischen und immunologischen Studien liefern.

Abstract

Postpartum uterine diseases, such as puerperal metritis and clinical endometritis may affect over 40 % of cows in dairy farms. Regardless of their severity, these diseases are one of the main reasons for impaired fertility, causing declines in dairy cow productivity and hence, resulting in economic losses. Although uterine diseases have been the topic of scientific discussion for many years, until now it was not possible to agree on uniform definitions for the different kinds of manifestation. By including technical innovations and testing procedures, enormous scientific progress and a deeper knowledge of the physiology as well as the pathologic mechanisms have been achieved. Bovine metritis and endometritis may be regarded as multifactorial diseases caused by a combination of microbial infection, the dysregulation of the immune system, and additional risk factors. These interactions have been analyzed on microbial and molecular biological levels as well as by the use of bioinformatics and molecular genetics. As a result, new species of bacteria and inflammatory mediators possibly contributing to the development of uterine diseases have recently been described. Additionally, metabolic and genetic risk factors and their roles in leading to fertility impairment have been evaluated. In conclusion, it was possible to identify new approaches for possible therapeutic and preventive methods, a subset of which may already be implemented into daily practical routine. This article provides an overview of recent scientific results concerning bovine metritis and endometritis with a focus on microbial, microbiological and immunological studies.

Schlüsselwörter

Metritis - Endometritis - Fruchtbarkeit - Puerperium - Pathomechanismen

Key words

Metritis - endometritis - fertility - puerperium - mechanism of pathology

Publication History

Received: 31 March 2020

Accepted: 14 May 2020

Article published online:
21 August 2020

• Literatur

• 1 Gilbert RO, Shin ST, Guard CL. et al. Prevalence of endometritis and its effects on reproductive performance of dairy cows. Theriogenology 2005; 64: 1879-1888 doi:10.1016/j.theriogenology.2005.04.022
• 2 Sheldon IM, Lewis GS, LeBlanc S. et al. Defining postpartum uterine disease in cattle. Theriogenology 2006; 65: 1516-1530 doi:10.1016/j.theriogenology.2005.08.021
• 3 Dubuc J, Duffield TF, Leslie KE. et al. Definitions and diagnosis of postpartum endometritis in dairy cows. J Dairy Sci 2010; 93: 5225-5233 doi:10.3168/jds.2010–3428
• 4 Wagener K, Gabler C, Drillich M. A review of the ongoing discussion about definition, diagnosis and pathomechanism of subclinical endometritis in dairy cows. Theriogenology 2017; 94: 21-30 doi:10.1016/j.theriogenology.2017.02.005
• 5 LeBlanc SJ, Duffield TF, Leslie KE. et al. Defining and Diagnosing Postpartum Clinical Endometritis and its Impact on Reproductive Performance in Dairy Cows. J Dairy Sci 2002; 85: 2223-2236 doi:10.3168/jds.S0022–0302(02)74302–6
• 6 Gobikrushanth M, Salehi R, Ambrose DJ. et al. Categorization of endometritis and its association with ovarian follicular growth and ovulation, reproductive performance, dry matter intake, and milk yield in dairy cattle. Theriogenology 2016; 86: 1842-1849 doi:10.1016/j.theriogenology.2016.06.003
• 7 Mohammed ZA, Mann GE, Robinson RS. Impact of endometritis on post-partum ovarian cyclicity in dairy cows. Vet J 2019; 248: 8-13 doi:10.1016/j.tvjl.2019.03.008
• 8 Overton M, Fetrow J. Economics of postpartum uterine health. Dairy Cattle Reproduction Council Annual Meeting and Convention. 2008: 39-43
• 9 Pothmann H, Prunner I, Wagener K. et al. The prevalence of subclinical endometritis and intrauterine infections in repeat breeder cows. Theriogenology 2015; 83: 1249-1253 doi:10.1016/j.theriogenology.​2015.01.013
• 10 Tison N, Bouchard E, DesCôteaux L. et al. Effectiveness of intrauterine treatment with cephapirin in dairy cows with purulent vaginal discharge. Theriogenology 2017; 89: 305-317 doi:10.1016/j.theriogenology.2016.09.007
• 11 Sheldon IM. The postpartum uterus. Vet Clin North Am Food Anim Pract 2004; 20: 569-591 doi:10.1016/j.cvfa.2004.06.008
• 12 Prunner I, Wagener K, Pothmann H. et al. Risk factors for uterine diseases on small- and medium-sized dairy farms determined by clinical, bacteriological, and cytological examinations. Theriogenology 2014; 82: 857-865 doi:10.1016/j.theriogenology.2014.06.015
• 13 Giuliodori MJ, Magnasco M, Magnasco RP. et al. Purulent vaginal discharge in grazing dairy cows: Risk factors, reproductive performance, and prostaglandin F2α treatment. J Dairy Sci 2017; 100: 3805-3815 doi:10.3168/jds.2016–11373
• 14 Dohmen MJW, Joop K, Sturk A. et al. Relationship between intra-uterine bacterial contamination, endotoxin levels and the development of endometritis in postpartum cows with dystocia or retained placenta. Theriogenology 2000; 54 (07) 1019-1032 doi:10.1016/s0093–691x(00)00410–6
• 15 Dubuc J, Duffield TF, Leslie KE. et al. Risk factors for postpartum uterine diseases in dairy cows. J Dairy Sci 2010; 93: 5764-5771 doi:10.3168/jds.2010–3429
• 16 Amos MR, Healey GD, Goldstone RJ. et al. Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperella pyogenes to uterine disease in cattle. Biol Reprod 2014; 90: 54 doi:10.1095/biolreprod.113.115972
• 17 Bisinotto RS, Greco LF, Ribeiro ES. et al. Influences of nutrition and metabolism on fertility of dairy cows. Animal Reproduction (Belo Horizonte) 2012; 9: 260-272
• 18 Sheldon IM, Cronin JG, Pospiech M. et al. Symposium review: Mechanisms linking metabolic stress with innate immunity in the endometrium. J Dairy Sci 2018; 101: 3655-3664 doi:10.3168/jds.2017–13135
• 19 Turner ML, Cronin JG, Noleto PG. et al. Glucose Availability and AMP-Activated Protein Kinase Link Energy Metabolism and Innate Immunity in the Bovine Endometrium. PloS one 2016; 11: e0151416-e0151416 doi:10.1371/journal.pone.0151416
• 20 Bicalho ML, Marques EC, Gilbert RO. et al. The association of plasma glucose, BHBA, and NEFA with postpartum uterine diseases, fertility, and milk production of Holstein dairy cows. Theriogenology 2017; 88: 270-282 doi:10.1016/j.theriogenology.2016.09.036
• 21 Ceciliani F, Lecchi C, Urh C. et al. Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows. J Proteomics 2018; 178: 92-106 doi:10.1016/j.jprot.2017.10.010
• 22 Griffin JFT, Hartigan PJ, Nunn WR. Non specific uterine infections and bovine fertility I. Infection patterns and endometritis during the first 7 weeks post-partum. Theriogenology 1974; 3: 91-106 doi:10.1016/0093–691x(74)90052–1
• 23 Földi J, Kulcsár M, Pécsi A. et al. Bacterial complications of postpartum uterine involution in cattle. Animal Reproduction Science 2006; 96: 265-281 doi:10.1016/j.anireprosci.2006.08.006
• 24 Sheldon IM, Dobson H. Postpartum uterine health in cattle. Anim Reprod Sci 2004; 82–83: 295-306 doi:10.1016/j.anireprosci.​2004.04.006
• 25 Sheldon IM, Noakes DE, Rycroft AN. et al. Influence of uterine bacterial contamination after parturition on ovarian dominant follicle selection and follicle growth and function in cattle. Reproduction 2002; 123 (06) 837-845 doi:10.1530/rep.0.1230837
• 26 Bicalho MLS, Machado VS, Oikonomou G. et al. Association between virulence factors of Escherichia coli, Fusobacterium necrophorum, and Arcanobacterium pyogenes and uterine diseases of dairy cows. Vet Microbiol 2012; 157: 125-131 doi:10.1016/j.vetmic.2011.11.034
• 27 Werner A, Suthar V, Plöntzke J. et al. Relationship between bacteriological findings in the second and fourth weeks postpartum and uterine infection in dairy cows considering bacteriological results. J Dairy Sci 2012; 95: 7105-7114 doi:10.3168/jds.2012–5627
• 28 Sens A, Heuwieser W. Presence of Escherichia coli, Trueperella pyogenes, alpha-hemolytic streptococci, and coagulase-negative staphylococci and prevalence of subclinical endometritis. J Dairy Sci 2013; 96: 6347-6354 doi:10.3168/jds.2013–6646
• 29 Wagener K, Grunert T, Prunner I. et al. Dynamics of uterine infections with Escherichia coli, Streptococcus uberis and Trueperella pyogenes in post-partum dairy cows and their association with clinical endometritis. Vet J 2014; 202: 527-532 doi:10.1016/j.tvjl.2014.08.023
• 30 Bromfield JJ, Santos JEP, Block J. et al. Physiology and endocrinology symposium: Uterine infection: Linking infection and innate immunity with infertility in the high-producing dairy cow. J Anim Sci 2015; 93: 2021-2033 doi:10.2527/jas.2014–8496
• 31 Karsch FJ, Battaglia DF, Breen KM. et al. Mechanisms for ovarian cycle disruption by immune/inflammatory stress. Stress 2002; 5: 101-112 doi:10.1080/10253890290027868
• 32 Herath S, Williams EJ, Lilly ST. et al. Ovarian follicular cells have innate immune capabilities that modulate their endocrine function. Reproduction 2007; 134: 683-693 doi:10.1530/REP-07–0229
• 33 Price JC, Sheldon IM. 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 2013; 89 doi:10.1095/biolreprod.113.110965
• 34 Herath S, Lilly ST, Fischer DP. et al. Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2alpha to prostaglandin E2 in bovine endometrium. Endocrinology 2009; 150: 1912-1920 doi:10.1210/en.2008–1379
• 35 Sheldon IM, Rycroft AN, Dogan B. et al. Specific strains of Escherichia coli are pathogenic for the endometrium of cattle and cause pelvic inflammatory disease in cattle and mice. PLoS One 2010; 5: e9192 doi:10.1371/journal.pone.0009192
• 36 Prunner I, Pothmann H, Wagener K. et al. Dynamics of bacteriologic and cytologic changes in the uterus of postpartum dairy cows. Theriogenology 2014; 82: 1316-1322 doi:10.1016/j.theriogenology.​2014.08.018
• 37 Westermann S, Drillich M, Kaufmann TB. et al. A clinical approach to determine false positive findings of clinical endometritis by vaginoscopy by the use of uterine bacteriology and cytology in dairy cows. Theriogenology 2010; 74: 1248-1255 doi:10.1016/j.theriogenology.​2010.05.028
• 38 Ruder CA, Sasser RG, Williams RJ. et al. Uterine infections in the postpartum cow: II. Possible synergistic effect of Fusobacterium necrophorum and Corynebacterium pyogenes. Theriogenology 1981; 15: 573-580 doi:10.1016/0093–691X(81)90060–1
• 39 Olson JD, Ball L, Mortimer RG. et al. Aspects of bacteriology and endocrinology of cows with pyometra and retained fetal membranes. Am J Vet Res 1984; 45: 2251-2255
• 40 Williams EJ, Fischer DP, Pfeiffer DU. et al. Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle. Theriogenology 2005; 63: 102-117 doi:10.1016/j.theriogenology.2004.03.017
• 41 Wagener K, Drillich M, Baumgardt S. et al. Falsiporphyromonas endometrii gen. nov., sp. nov., isolated from the post-partum bovine uterus, and emended description of the genus Porphyromonas Shah and Collins 1988. Int J Syst Evol Microbiol 2014; 64: 642-649 doi:10.1099/ijs.0.057307–0
• 42 Wagener K, Prunner I, Pothmann H. et al. Diversity and health status specific fluctuations of intrauterine microbial communities in postpartum dairy cows. Vet Microbiol 2015; 175: 286-293 doi:10.1016/j.vetmic.2014.11.017
• 43 Grunert T, Wenning M, Barbagelata MS. et al. Rapid and reliable identification of Staphylococcus aureus capsular serotypes by means of artificial neural network-assisted Fourier transform infrared spectroscopy. J Clin Microbiol 2013; 51: 2261-2266 doi:10.1128/JCM.00581–13
• 44 Grunert T, Wenning M, Barbagelata MS. et al. Rapid and Reliable Identification of Staphylococcus aureus Capsular Serotypes by Means of Artificial Neural Network-Assisted Fourier Transform Infrared Spectroscopy. J Clin Microbiol 2013; 51: 2261 doi:10.1128/JCM.00581–13
• 45 Kaeberlein T, Lewis K, Epstein SS. Isolating “Uncultivable” Microorganisms in Pure Culture in a Simulated Natural Environment. Science 2002; 296: 1127 doi:10.1126/science.1070633
• 46 Karstrup CC, Klitgaard K, Jensen TK. et al. Presence of bacteria in the endometrium and placentomes of pregnant cows. Theriogenology 2017; 99: 41-47 doi:10.1016/j.theriogenology.2017.05.013
• 47 Santos TM, Gilbert RO, Bicalho RC. Metagenomic analysis of the uterine bacterial microbiota in healthy and metritic postpartum dairy cows. J Dairy Sci 2011; 94: 291-302 doi:10.3168/jds.2010–3668
• 48 Jeon SJ, Vieira-Neto A, Gobikrushanth M. et al. Uterine Microbiota Progression from Calving until Establishment of Metritis in Dairy Cows. Appl Environ Microbiol 2015; 81: 6324-6332 doi:10.1128/AEM.01753–15
• 49 Galvao KN, Bicalho RC, Jeon SJ. Symposium review: The uterine microbiome associated with the development of uterine disease in dairy cows. J Dairy Sci 2019; 102: 11786-11797 doi:10.3168/jds.2019–17106
• 50 Knudsen LRV, Karstrup CC, Pedersen HG. et al. Revisiting bovine pyometra – New insights into the disease using a culture-independent deep sequencing approach. Vet Microbiol 2015; 175: 319-324 doi:10.1016/j.vetmic.2014.12.006
• 51 Bicalho MLS, Lima S, Higgins CH. et al. Genetic and functional analysis of the bovine uterine microbiota. Part II: Purulent vaginal discharge versus healthy cows. J Dairy Sci 2017; 100: 3863-3874 doi:10.3168/jds.2016–12061
• 52 Santos TM, Bicalho RC. Diversity and succession of bacterial communities in the uterine fluid of postpartum metritic, endometritic and healthy dairy cows. PLoS One 2012; 7: e53048 doi:10.1371/journal.pone.0053048
• 53 Peter S, Gartner MA, Michel G. et al. Influence of intrauterine administration of Lactobacillus buchneri on reproductive performance and pro-inflammatory endometrial mRNA expression of cows with subclinical endometritis. Sci Rep 2018; 8: 5473 doi:10.1038/s41598–018–22856-y
• 54 Velazquez MML, Peralta MB, Angeli E. et al. Immune status during postpartum, peri-implantation and early pregnancy in cattle: An updated view. Anim Reprod Sci 2019; 206: 1-10 doi:10.1016/j.anireprosci.​2019.05.010
• 55 Sheldon IM, Cronin JG, Bromfield JJ. Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle. Annu Rev Anim Biosci 2019; 7: 361-384 doi:10.1146/annurev-animal-020518–115227
• 56 Sheldon IM, Molinari PCC, Ormsby TJR. et al. Preventing postpartum uterine disease in dairy cattle depends on avoiding, tolerating and resisting pathogenic bacteria. Theriogenology 2020; 150: 158-165 doi:10.1016/j.theriogenology.2020.01.017
• 57 Herath S, Lilly ST, Santos NR. et al. Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reprod Biol Endocrinol 2009; 7: 55 doi:10.1186/1477–7827–7-55
• 58 Gabler C, Drillich M, Fischer C. et al. Endometrial expression of selected transcripts involved in prostaglandin synthesis in cows with endometritis. Theriogenology 2009; 71: 993-1004 doi:10.1016/j.theriogenology.2008.11.009
• 59 Kim IH, Kang HG, Jeong JK. et al. Inflammatory cytokine concentrations in uterine flush and serum samples from dairy cows with clinical or subclinical endometritis. Theriogenology 2014; 82: 427-432 doi:10.1016/j.theriogenology.2014.04.022
• 60 Wagener K, Pothmann H, Prunner I. et al. Endometrial mRNA expression of selected pro-inflammatory factors and mucins in repeat breeder cows with and without subclinical endometritis. Theriogenology 2017; 90: 237-244 doi:10.1016/j.theriogenology.2016.12.013
• 61 Gabler C, Fischer C, Drillich M. et al. Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum. Reprod Biol Endocrinol 2010; 8: 152 doi:10.1186/1477–7827–8-152
• 62 Fischer C, Drillich M, Odau S. et al. Selected pro-inflammatory factor transcripts in bovine endometrial epithelial cells are regulated during the oestrous cycle and elevated in case of subclinical or clinical endometritis. Reprod Fertil Dev 2010; 22: 818-829 doi:10.1071/rd09120
• 63 Galvao KN, Santos NR, Galvao JS. et al. Association between endometritis and endometrial cytokine expression in postpartum Holstein cows. Theriogenology 2011; 76: 290-299 doi:10.1016/j.theriogenology.2011.02.006
• 64 Peter S, Michel G, Hahn A. et al. Puerperal influence of bovine uterine health status on the mRNA expression of pro-inflammatory factors. J Physiol Pharmacol 2015; 66 (03) 449-462
• 65 Alhussien MN, Dang AK. Potential roles of neutrophils in maintaining the health and productivity of dairy cows during various physiological and physiopathological conditions: a review. Immunol Res 2019; 67: 21-38 doi:10.1007/s12026–019–9064–5
• 66 Zerbe H, Schuberth HJ, Engelke F. et al. Development and comparison of in vivo and in vitro models for endometritis in cows and mares. Theriogenology 2003; 60: 209-223 doi:10.1016/S0093–691X(02)01376–6
• 67 Dhaliwal GS, Murray RD, Woldehiwet Z. Some aspects of immunology of the bovine uterus related to treatments for endometritis. Anim Reprod Sci 2001; 67: 135-152 doi:10.1016/S0378–4320(01)00124–5
• 68 Hammon DS, Evjen IM, Dhiman TR. et al. Neutrophil function and energy status in Holstein cows with uterine health disorders. Vet Immunol Immunopathol 2006; 113: 21-29 doi:10.1016/j.vetimm.2006.03.022
• 69 Galvao KN, Flaminio MJ, Brittin SB. et al. Association between uterine disease and indicators of neutrophil and systemic energy status in lactating Holstein cows. J Dairy Sci 2010; 93: 2926-2937 doi:10.3168/jds.2009–2551
• 70 Drillich M, Tesfaye D, Rings F. et al. Effects of polymorphonuclear neutrophile infiltration into the endometrial environment on embryonic development in superovulated cows. Theriogenology 2012; 77: 570-578 doi:10.1016/j.theriogenology.2011.08.033
• 71 Salasel B, Mokhtari A, Taktaz T. Prevalence, risk factors for and impact of subclinical endometritis in repeat breeder dairy cows. Theriogenology 2010; 74: 1271-1278 doi:10.1016/j.theriogenology.2010.05.033
• 72 Kasimanickam R, Kasimanickam V, Kastelic JP. Mucin 1 and cytokines mRNA in endometrium of dairy cows with postpartum uterine disease or repeat breeding. Theriogenology 2014; 81: 952-958e2 doi:10.1016/j.theriogenology.2014.01.018
• 73 Carson DD, Bagchi I, Dey SK. et al. Embryo Implantation. Development Biol 2000; 223: 217-237 doi:10.1006/dbio.2000.9767
• 74 Besenfelder U, Havlicek V, Kuzmany A. et al. Endoscopic approaches to manage in vitro and in vivo embryo development: use of the bovine oviduct. Theriogenology 2010; 73: 768-776 doi:10.1016/j.theriogenology.2009.07.003
• 75 Pothmann H, Havlicek V, Besenfelder U. et al. Different methods for in situ collection of samples from the bovine oviduct. In: 21st Annual Conference of the European-Society-for-Domestic-Animal-Reproduction (ESDAR), Bern, Switzerland, August 24–26, 2017.
• 76 Machado VS, Bicalho ML, de Souza Meira Junior EB. et al. Subcutaneous immunization with inactivated bacterial components and purified protein of Escherichia coli, Fusobacterium necrophorum and Trueperella pyogenes prevents puerperal metritis in Holstein dairy cows. PloS one 2014; 9: e91734-e91734 doi:10.1371/journal.pone.0091734
• 77 Pascottini OB, LeBlanc SJ. Modulation of immune function in the bovine uterus peripartum. Theriogenology 2020; 150: 193-200 doi:10.1016/j.theriogenology.2020.01.042
• 78 Canning P, Hassfurther R, TerHune T. et al. Efficacy and clinical safety of pegbovigrastim for preventing naturally occurring clinical mastitis in periparturient primiparous and multiparous cows on US commercial dairies. J Dairy Sci 2017; 100: 6504-6515 doi:10.3168/jds.2017–12583
• 79 Ruiz R, Tedeschi LO, Sepúlveda A. Investigation of the effect of pegbovigrastim on some periparturient immune disorders and performance in Mexican dairy herds. J Dairy Sci 2017; 100: 3305-3317 doi:10.3168/jds.2016–12003
• 80 Freick M, Zenker M, Passarge O. et al. Reducing the incidence of acute puerperal metritis in primiparous cows by application of pegbovigrastim in a Holstein dairy herd. Veterinární Medicína 2018; 63: 151-160 doi:10.17221/2/2018-vetmed
• 81 Zinicola M, Korzec H, Teixeira AGV. et al. Effects of pegbovigrastim administration on periparturient diseases, milk production, and reproductive performance of Holstein cows. J Dairy Sci 2018; 101: 11199-11217 doi:10.3168/jds.2018–14869
• 82 Zinicola M, Bicalho MLS, Santin T. et al. Effects of recombinant bovine interleukin-8 (rbIL-8) treatment on health, metabolism, and lactation performance in Holstein cattle II: Postpartum uterine health, ketosis, and milk production. J Dairy Sci 2019; 102: 10316-10328 doi:10.3168/jds.2019–16335
• 83 Bretzlaff K. Rationale for Treatment of Endometritis in the Dairy Cow. Vet Clin North Am: Food Anim Pract 1987; 3: 593-607 doi:10.1016/S0749–0720(15)31132–4
• 84 Grüssel T, Busch W. Behavioral response of cows after intrauterine application of disinfectants for treatment of endometritis. Tierarztl Prax Ausg G Grosstiere Nutztiere 1998; 26: 67-72
• 85 Nakao T, Moriyoshi M, Kawata K. Effect of postpartum intrauterine treatment with 2 % polyvinyl-pyrrolidone-iodine solution on reproductive efficiency in cows. Theriogenology 1988; 30: 1033-1043 doi:10.1016/0093–691X(88)90277–4
• 86 Haimerl P, Heuwieser W, Arlt S. Short communication: Meta-analysis on therapy of bovine endometritis with prostaglandin F2α – An update. J Dairy Sci 2018; 101: 10557-10564 doi:10.3168/jds.2018–14933
• 87 Kaniyamattam K, De Vries A, Tauer LW. et al. Economics of reducing antibiotic usage for clinical mastitis and metritis through genomic selection. J Dairy Sci 2020; 103: 473-491 doi:10.3168/jds.2018–15817