A Transcriptome Analysis: Various Reasons of Adverse Pregnancy Outcomes Caused by Acute Toxoplasma gondii Infection

Abstract

Background: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite, which can affect the pregnancy outcomes in infected females by damaging the uterus, and the intrauterine environment as well as and the hypothalamus resulting in hormonal imbalance. However, the molecular mechanisms underlying the parasite-induced poor pregnancy outcomes and the key genes regulating these mechanisms remain unclear. Therefore, this study aimed to analyze the gene expression in the mouse's uterus following experimentally-induced acute infection with T. gondii RH strain. Three groups of female mice were intraperitoneally injected with tachyzoites as follow; 3 days before pregnancy (FBD6), after pregnancy (FAD6), and after implantation (FID8) as the experimental groups. Another corresponding three groups served as control, were injected with normal saline at the same time. Transcriptome analysis of the total RNA extracted from both infected and non-infected mouse uterus samples was performed using RNA sequencing (RNA-Seq).Results: The three experimental groups (FBD6, FAD6, and FID8) had a total of 4,561, 2,345, and 2,997 differentially expressed genes (DEGs) compared to the controls. The significantly upregulated and downregulated DEGs were 2,571 and 1,990 genes in FBD6, 1,042 and 1,303 genes in FAD6 and 1,162 and 1,835 genes in FID8 group, respectively. The analysis of GO annotation, and KEGG pathway showed that DEGs were mainly involved in anatomical structure development, transport, cell differentiation, embryo development, hormone biosynthetic process, signal transduction, immune system process, phagosome, pathways in cancer, and cytokine-cytokine receptor interaction pathways. Frontiers in Physiology | www.frontiersin.org February 2020 | Volume 11 | Article 115 Zhou et al. Adverse Pregnancy and T. gondii InfectionConclusion: T. gondii infection can induce global transcriptomic changes in the uterus that may cause pregnancy hypertension, destruct the intrauterine environment, and hinder the normal development of placenta and embryo. Our results may help to understand the molecular mechanisms of the acute T. gondii infection, which could promote the development of new therapeutics or prophylactics for toxoplasmosis in pregnancy.Abbreviations: CD6A, mice injected with normal saline (NS) 3 days after pregnancy; CD6B, mice injected with NS 3 days before pregnancy; CD8, mice injected with NS in the fifth day of pregnancy; DEGs, differentially expressed genes; FAD6, mice infected with T. gondii 3 days after pregnancy; FBD6, mice infected with T. gondii 3 days before pregnancy; FID8, mice infected with T. gondii on the fifth day of pregnancy.

Cluster analysis of splenocyte microRNAs in the pig reveals key signal regulators of immunomodulation in the host during acute and chronic Toxoplasma gondii infection

“…Nonetheless, H-subcluster-specific KEGG pathways related to immune responses against T. gondii infection were still found, especially in subcluster H2. As previously reported [ 30 , 55 , 56 ], cytokine–cytokine receptor interaction (ssc04060) was found to be involved in immunomodulation of the host during acute and chronic T. gondii infection in the current study. A total of 52 genes of the pathway involving chemokines including CC and CXC subfamilies, class I helical cytokines, class II helical IL10/28-like cytokines, IL1-like cytokines, IL17-like cytokines, TNF family, and TGF-β family were potentially targeted by 31 miRNAs in subcluster H2 (Additional file 17 : Table S16).…”

“…This indicates that the interactions amongst cytokines play a crucial role in the balance of the immune microenvironment during the different infection stages, such as preventing excessive immunity in acute infection and maintaining the level of inflammation to control the reactivation of T. gondii in chronic infection. In addition, several previous researchers found that the cytokine–cytokine receptor interaction pathway was also influenced by different T. gondii strains during challenge in various infection models including cat, mouse, and human cells [ 30 , 55 , 56 ], suggesting a common feature wherein interactions between cytokines and cytokine receptors have extremely important roles in the host immune responses against T. gondii , and are not strictly host-specific or strain-specific. Nonetheless, our analysis revealed that miRNAs in subcluster H2 involved in the cytokine–cytokine receptor interaction pathway may be the important immunomodulatory molecules of the host during T. gondii infection.…”

Transcriptomic Profiling of Mouse Brain During Acute and Chronic Infections by Toxoplasma gondii Oocysts

“…Data supporting this view are emerging from various "-omics"-based profiling of the brains of mice infected by T. gondii (Jia et al, 2013;Tanaka et al, 2013;Pittman et al, 2014;Zhou et al, 2015;Hu et al, 2018;Garfoot et al, 2019a;Ma et al, 2019). The magnitude of this challenge has increased the interest in understanding how T. gondii infection affects murine host at the transcriptional level in various tissues other than the brain, including the liver (He et al, 2016a), spleen (He et al, 2016b,c), peripheral lymphocytes (Jia et al, 2013), and the uterus (Zhou et al, 2020). Increased understanding of the brain transcriptomic signature associated with T. gondii infection can provide new testable hypotheses that may ultimately facilitate the development of new treatment interventions to control cerebral toxoplasmosis.…”

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

“…In this study, using the PubMed database [ 69 ], we compiled all the transcriptomes (that we could find) of hypertensive versus normotensive animals, as presented in Table 4 . The total number of DEGs was 4216 in 14 tissues of four animal species, as cited in the rightmost column of Table 4 [ 7 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ].…”

“…Parents of half of the hypertensive patients had hypertension, but all the known (>60) hypertension-related whole-genome human loci explained only 3% of this heritability of hypertension [ 25 ]. Maybe this is why mainstream transcriptome-profiling studies on hypertensive versus normotensive patients [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and animals [ 7 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ] are focused on the differentially expressed genes (DEGs) that are specific to gender, age, and the stage of hypertension development. This is needed in predictive preventive personalized participatory (4P) medicine [ 58 ] to estimate where, how, why, and when hypertension might occur in a given patient depending on his/her genetic background.…”