Abstract
Neospora caninum is a protozoan parasite which can infect a range of animals, including dogs, cattle, and sheep. Bovine neosporosis, which mainly causes abortion in cattle, results in substantial economic losses worldwide. To study the effects of N. caninum infection on the placenta, a pregnant mouse model for N. caninum infection was established. The litter size (8.6 ± 1.5) and the number of live pups (6.4 ± 1.8) of infected dams were significantly lower compared with those of non-infected dams. Trophoblast cell shrinkage and a large number of apoptosomes were detected in the placentas of the infected group. The parasite load in the placental tissue was significantly higher with time after infection. Likewise, apoptosis of placental trophoblast cells significantly increased with time after infection. Among the 66 apoptotic genes detected in this study, eight genes, including Bcl-2, were significantly differentially expressed by about > tenfold in infected and uninfected mice. The expression of BAX and tumor necrosis factor-alpha (TNF-α) was upregulated in the placental cells of the infected mice, whereas the expression of BCL-2 was downregulated. Enzyme-linked immunosorbent assays (ELISAs) showed that apoptotic protease caspase-3 level was significantly increased in placental cell suspension, and insulin-like growth factor (IGF)-2 level was significantly reduced. Acetylcholine (ACH) and placental prolactin (PL) levels were initially decreased but eventually increased. In summary, infection of mice with N. caninum caused apoptotic damage to the placental tissues, cells, and genes and affected the normal physiological functions of placenta, which may largely explain the adverse pregnancy outcomes caused by N. caninum infection in mice.
Similar content being viewed by others
Data availability
All data generated or analyzed during this study are included in this published article.
References
Abrahams VM, Kim YM, Straszewski SL, Romero R, Mor G (2004) Macrophages and apoptotic cell clearance during pregnancy: decidual macrophage function during pregnancy. Am J Reprod Immunol 51:275–282. https://doi.org/10.1111/j.1600-0897.2004.00156.x
Almería S, Serrano-Perez B, Darwich L, Domingoab M, Mur-Novalesc R et al (2016) Foetal death in naive heifers inoculated with Neospora caninum isolate Nc-Spain7 at 110 days of pregnancy. Exp Parasitol 168:62–69. https://doi.org/10.1016/j.exppara.2016.06.009
Amini L, Namavari M, Khodakaram-Tafti A, Divarc MR, Hosseinib SMH (2020) The evaluation of attenuated Neospora caninum by long-term passages on murine macrophage cell line in prevention of vertical transmission in mice. Vet Parasitol 283:109171. https://doi.org/10.1016/j.vetpar.2020.109171
Arranz-Solís D, Benavides J, Regidor-Cerrillo J, Horcajo P, Castaño P et al (2016) Systemic and local immune responses in sheep after Neospora caninum experimental infection at early, mid and late gestation. Vet Res 47:2. https://doi.org/10.1186/s13567-015-0290-0
Bartley PM, Guido S, Mason C, Stevenson H, Chianini F et al (2019) Detection of Neospora caninum DNA in cases of bovine and ovine abortion in the South-West of Scotland. Parasitology 146:979–982. https://doi.org/10.1017/S0031182019000301
Bjerkås I, Mohn SF, Presthus J (1984) Unidentified cyst-forming sporozoon causing encephalomyelitis and myositis in dogs. Z Parasitenkd 70:271–274. https://doi.org/10.1007/BF00942230
Botta C, Pellegrini G, Hässig M, Pesch T, Prähauser B et al (2019) Bovine fetal placenta during pregnancy and the postpartum period. Vet Pathol 56:248–258. https://doi.org/10.1177/0300985818806453
Cantón GJ, Katzer F, Maley SW, Bartley PM, Benavides-Silván J et al (2014) Inflammatory infiltration into placentas of Neospora caninum challenged cattle correlates with clinical outcome of pregnancy. Vet Res 45:11. https://doi.org/10.1186/1297-9716-45-11
Caspe SG, Moore DP, Leunda MR, Canoa DB, Lischinskya L et al (2012) The Neospora caninum-spain 7 isolate induces placental damage, fetal death and abortion in cattle when inoculated in early gestation. Vet Parasitol 189:171–181. https://doi.org/10.1016/j.vetpar.2012.04.034
Collantes-Fernandez E, Arrighi RBG, Álvarez-García G, Weidner JM, Regidor-Cerrillo J et al (2012) Infected dendritic cells facilitate systemic dissemination and transplacental passage of the obligate intracellular parasite Neospora caninum in mice. PLoS One 7:e32123. https://doi.org/10.1371/journal.pone.0032123
Debierre-Grockiego F, Hippe D, Schwarz RT, Lüder CGK (2007) Toxoplasma gondii glycosylphosphatidylinositols are not involved in T. gondii-induced host cell survival. Apoptosis 12:781–790. https://doi.org/10.1007/s10495-006-0038-4
Donahoe SL, Lindsay SA, Krockenberger M, Phalen D, Šlapeta J (2015) A review of neosporosis and pathologic findings of Neospora caninum infection in wildlife. Int J Parasitol Parasites Wildl 4:216–238. https://doi.org/10.1016/j.ijppaw.2015.04.002
Ferro EAV, Silva DAO, Bevilacqua E, Mineo JR (2002) Effect of Toxoplasma gondii infection kinetics on trophoblast cell population in Calomys callosus, a model of congenital toxoplasmosis. Infect Immun 70:7089–7094. https://doi.org/10.1128/IAI.70.12.7089-7094.2002
González-Warleta M, Castro-Hermida JA, Calvo C, Pérez V, Gutiérrez-Expósito D et al (2018) Endogenous transplacental transmission of Neospora caninum during successive pregnancies across three generations of naturally infected sheep. Vet Res 49:106. https://doi.org/10.1186/s13567-018-0601-3
Hemphill A, Aguado-Martínez A, Müller J (2016) Approaches for the vaccination and treatment of Neospora caninum infections in mice and ruminant models. Parasitology 143:245–259. https://doi.org/10.1017/S0031182015001596
Jia L, Xie S, Li J, Li H, Wang H et al (2020) Establishment of a model of Neospora caninum infection in pregnant mice. Parasitol Res 119:3829–3837. https://doi.org/10.1007/s00436-020-06903-0
Jia LJ, Zhang SF, Liu MM, Qian NC, Guo HP (2014) Isolation, identification, and pathogenicity of Neospora caninum China Yanbian strain. Iran J Parasitol 9:394–401
Juliano PB, Blotta MHSL, Altemani AMA (2006) ICAM-1 is overexpressed by villous trophoblasts in placentitis. Placenta 27:750–757. https://doi.org/10.1016/j.placenta.2005.07.008
Lagomarsino H, Scioli A, Rodríguez A, Armendano J, Fiorani F et al (2019) Controlling endemic Neospora caninum-related abortions in a dairy herd from argentina. Front Vet Sci 6:446. https://doi.org/10.3389/fvets.2019.00446
Lefkaditis M, Mpairamoglou R, Sossidou A, Spanoudis K, Tsakiroglou M (2020) Neospora caninum, a potential cause of reproductive failure in dairy cows from Northern Greece. Vet Parasitol: Reg Stud Rep 19:100365. https://doi.org/10.1016/j.vprsr.2019.100365
López-Pérez IC, Collantes-Fernández E, Aguado-Martínez A, Rodríguez-Bertosb A, Ortega-Mora LM (2008) Influence of Neospora caninum infection in BALB/c mice during pregnancy in post-natal development. Vet Parasitol 155:175–183. https://doi.org/10.1016/j.vetpar.2008.05.018
Nardoni S, Poli A, Varvaro I, Rocchigiani G, Ceccherelli R et al (2019) Detection of Neospora caninum DNA in wild birds from Italy. Pathogens 8:202. https://doi.org/10.3390/pathogens8040202
Nelson DM (1996) Apoptotic changes occur in syncytiotrophoblast of human placental villi where fibrin type fibrinoid is deposited at discontinuities in the villous trophoblast. Placenta 17:387–391. https://doi.org/10.1016/S0143-4004(96)90019-3
Nishikawa Y, Shimoda N, Fereig RM, Moritaka T, Umeda K et al (2018) Neospora caninum dense granule protein 7 regulates the pathogenesis of neosporosis by modulating host immune response. Appl Environ Microbiol 84:e01350-e1418. https://doi.org/10.1128/AEM.01350-18
Regidor-Cerrillo J, Gómez-Bautista M, Del Pozo I, Jiménez-Ruiz E, Aduriz G et al (2010) Influence of Neospora caninum intra-specific variability in the outcome of infection in a pregnant BALB/c mouse model. Vet Res 41:52. https://doi.org/10.1051/vetres/2010024
Shamas-Din A, Kale J, Leber B, Andrews DW (2013) Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol 5:a008714–a008714. https://doi.org/10.1101/cshperspect.a008714
Yue H-P (2012) Investigate on regulative impact of the hormone of the placenta infected with Toxoplasma gondii. Dissertation, Shanxi Medical University
Acknowledgements
We appreciate Galon Eloiza May’s help with the language during the development of this manuscript.
Funding
The research was supported by the National Natural Science Foundation of China (32160839), the Scientific Research and Innovation Team Project of Yanbian University, and the Leading Talents and Teams of Young and Middle-aged Technological Innovation in Jilin Province (20200301034RQ) and supported by the 111 Project (D20034).
Author information
Authors and Affiliations
Contributions
Conceptualization: Lijun Jia, Zeyu Tang, Hang Li, Suzhu Xie, Shaowei Zhao; methodology: Lijun Jia, Zeyu Tang; investigation: Lijun Jia, Hang Li, Suzhu Xie, Shaowei Zha; data analysis: Shuang Zhang, Hao Wang, Nanli Li, Xuancheng Zhang, Fanglin Zhao; writing-—original draft: Zeyu Tang, Hang Li, Suzhu Xie, Shaowei Zhao; writing—review and editing: All authors; project administration and supervision: Lijun Jia
Corresponding author
Ethics declarations
Ethics approval
All animal experimental procedures were approved by the Ethical Committee for the Experimental Use of Animals at Yanbian University (Yanji, China) in accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals of the Ministry of Science and Technology of China (approval no.: 20180301).
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Conflict of interest
The authors declare no competing interests.
Additional information
Handling Editor: Una Ryan
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Zeyu Tang, Hang Li, Suzhu Xie, and Shaowei Zhao have contributed equally to this work and share first authorship.
Supplementary Information
ESM 1
(PNG 110 kb)
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Tang, Z., Li, H., Xie, S. et al. A preliminary study on placental damage associated to experimental neosporosis in BALB/c mice. Parasitol Res 122, 781–788 (2023). https://doi.org/10.1007/s00436-022-07771-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-022-07771-6