Comparative proteomic analysis of trophoblast cell models reveals their differential phenotypes, potential uses, and limitations

Szklanna, Paulina B.; Wynne, Kieran; Nolan, Marie T.; Egan, Karl; Áinle, Fionnuala Ní; Maguire, Patricia B.

doi:10.1002/pmic.201700037

Cited by 18 publications

(12 citation statements)

References 26 publications

(48 reference statements)

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“…In total, 1192 bovine proteins were identified and quantified. This number of identified and quantified proteins is comparable to that in other studies in trophoblastic cell lines [12]. We also identified and quantified 334 N. caninum proteins.…”

Section: Neospora Caninum and Bovine Trophoblast Cell Proteomessupporting

confidence: 83%

Proteomic Characterization of Host-Pathogen Interactions during Bovine Trophoblast Cell Line Infection by Neospora caninum

et al. 2020

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Despite the importance of bovine neosporosis, relevant knowledge gaps remain concerning the pathogenic mechanisms of Neospora caninum. Infection of the placenta is a crucial event in the pathogenesis of the disease; however, very little is known about the relation of the parasite with this target organ. Recent studies have shown that isolates with important variations in virulence also show different interactions with the bovine trophoblast cell line F3 in terms of proliferative capacity and transcriptome host cell modulation. Herein, we used the same model of infection to study the interaction of Neospora with these target cells at the proteomic level using LC-MS/MS over the course of the parasite lytic cycle. We also analysed the proteome differences between high- (Nc-Spain7) and low-virulence (Nc-Spain1H) isolates. The results showed that mitochondrial processes and metabolism were the main points of Neospora-host interactions. Interestingly, Nc-Spain1H infection showed a higher level of influence on the host cell proteome than Nc-Spain7 infection.

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Section: Neospora Caninum and Bovine Trophoblast Cell Proteomessupporting

confidence: 83%

Proteomic Characterization of Host-Pathogen Interactions during Bovine Trophoblast Cell Line Infection by Neospora caninum

et al. 2020

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“…Multiple studies have reported that HTR-8/SVneo cells retain key functional characteristics of extravillous trophoblasts such as invasive and proliferative capacities which change in response to stress and oxygen availability, expression of adhesion molecules and a mesenchymal proteomic phenotype (Kilburn et al , 2000; Hannan et al , 2010; Liu et al , 2016a; Szklanna et al , 2017). In addition, several studies have also shown that HTR-8/SVneo cells express specific markers that uniquely identify extravillous trophoblasts including cytokeratin 7 (CK7) and α5β1 integrin, and when grown on matrigel, histocompatibility antigen, class I, G (HLA-G) (Irving et al , 1995; Kilburn et al , 2000; Khan et al , 2011; Takao et al , 2011).…”

Section: Resultsmentioning

confidence: 99%

Trichloroethylene metabolite S-(1,2-dichlorovinyl)- l -cysteine induces lipid peroxidation-associated apoptosis via the intrinsic and extrinsic apoptosis pathways in a first-trimester placental cell line

Elkin

Harris

Loch‐Caruso

2018

Toxicology and Applied Pharmacology

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Trichloroethylene (TCE), a prevalent environmental contaminant, is a potent renal and hepatic toxicant through metabolites such as S-(1, 2-dichlorovinyl)-l-cysteine (DCVC). However, effects of TCE on other target organs such as the placenta have been minimally explored. Because elevated apoptosis and lipid peroxidation in placenta have been observed in pregnancy morbidities involving poor placentation, we evaluated the effects of DCVC exposure on apoptosis and lipid peroxidation in a human extravillous trophoblast cell line, HTR-8/SVneo. We exposed the cells in vitro to 10-100μM DCVC for various time points up to 24h. Following exposure, we measured apoptosis using flow cytometry, caspase activity using luminescence assays, gene expression using qRT-PCR, and lipid peroxidation using a malondialdehyde quantification assay. DCVC significantly increased apoptosis in time- and concentration-dependent manners (p<0.05). DCVC also significantly stimulated caspase 3, 7, 8 and 9 activities after 12h (p<0.05), suggesting that DCVC stimulates the activation of both the intrinsic and extrinsic apoptotic signaling pathways simultaneously. Pre-treatment with the tBID inhibitor Bl-6C9 partially reduced DCVC-stimulated caspase 3 and 7 activity, signifying crosstalk between the two pathways. Additionally, DCVC treatment increased lipid peroxidation in a concentration-dependent manner. Co-treatment with the antioxidant peroxyl radical scavenger (±)-α-tocopherol attenuated caspase 3 and 7 activity, suggesting that lipid peroxidation mediates DCVC-induced apoptosis in extravillous trophoblasts. Our findings suggest that DCVC-induced apoptosis and lipid peroxidation in extravillous trophoblasts could contribute to poor placentation if similar effects occur in vivo in response to TCE exposure, indicating that further studies into this mechanism are warranted.

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“…The complex is important for early embryo development and preimplantation in pigs and mice 107,108 . ARPC2 expression has been identified in the BeWo trophoblastic cell line used to investigate placental function 109 and is subject to RNA editing in placentas associated with intrauterine growth restriction/small for gestational age (SGA) 110 . Overall, genes associated with the variant rs10932774 ( PNKD, TMBIM1 and ARPC2 ) show long-term evolutionary conservation consistent with a signature of balancing selection and prior research suggests links to pregnancy through a variety of mechanisms.…”

Section: Resultsmentioning

confidence: 99%

Accounting for diverse evolutionary forces reveals the mosaic nature of selection on genomic regions associated with human preterm birth

LaBella

Abraham

Pichkar

et al. 2019

Preprint

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35Human pregnancy requires the coordinated function of multiple tissues in both mother and fetus and has 36 evolved in concert with major human adaptations. As a result, pregnancy-associated phenotypes and 37 related disorders are genetically complex and have likely been sculpted by diverse evolutionary forces. 38 However, there is no framework to comprehensively evaluate how these traits evolved or to explore the 39 relationship of evolutionary signatures on trait-associated genetic variants to molecular function. Here we 40develop an approach to test for signatures of diverse evolutionary forces, including multiple types of 41 selection, and apply it to genomic regions associated with spontaneous preterm birth (sPTB), a complex 42 disorder of global health concern. We find that sPTB-associated regions harbor diverse evolutionary 43 signatures including evolutionary sequence conservation (consistent with the action of negative selection), 44 excess population differentiation (local adaptation), accelerated evolution (positive selection), and 45 balanced polymorphism (balancing selection). Furthermore, these genomic regions show diverse 46 functional characteristics which enables us to use evolutionary and molecular lines of evidence to develop 47 54Mammalian pregnancy requires the coordination of multiple maternal and fetal tissues 1,2 and extensive 55 modulation of the maternal immune system so that the genetically distinct fetus is not immunologically 56 rejected 3 . Given this context, pregnancy-related phenotypes and disorders are likely to have experienced 57 diverse selective pressures. This is particularly likely on the human lineage where pregnancy has been 58 shaped by unique human adaptations such as bipedality and enlarged brain size 4-8 . One major disorder of 59 pregnancy is preterm birth (PTB), a complex multifactorial syndrome 9 that affects 10% of pregnancies in 60 the United States and more than 15 million pregnancies worldwide each year 10,11 . PTB leads to increased 61 infant mortality rates and significant short-and long-term morbidity [11][12][13][14] . Risk for PTB varies 62 substantially with race, environment, comorbidities, and genetic factors 15 . PTB is broadly classified into 63 iatrogenic PTB, when it is associated with medical conditions such as preeclampsia (PE) or intrauterine 64 growth restriction (IUGR), and spontaneous PTB (sPTB), which occurs in the absence of preexisting 65 medical conditions or is initiated by preterm premature rupture of membranes [16][17][18][19] . The biological 66 pathways contributing to sPTB remain poorly understood 9 , but diverse lines of evidence suggest that 67 maternal genetic variation is an important contributor 20-24 . 68The complexity of human pregnancy and association with unique human adaptations raise the hypothesis 69 that genetic variants associated with birth timing and sPTB have been shaped by diverse evolutionary 70 forces. Consistent with this hypothesis, several immune genes involved in pregnancy have signatures of 71 recent purifyin...

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Comparative proteomic analysis of trophoblast cell models reveals their differential phenotypes, potential uses, and limitations

Cited by 18 publications

References 26 publications

Proteomic Characterization of Host-Pathogen Interactions during Bovine Trophoblast Cell Line Infection by Neospora caninum

Proteomic Characterization of Host-Pathogen Interactions during Bovine Trophoblast Cell Line Infection by Neospora caninum

Trichloroethylene metabolite S-(1,2-dichlorovinyl)- l -cysteine induces lipid peroxidation-associated apoptosis via the intrinsic and extrinsic apoptosis pathways in a first-trimester placental cell line

Accounting for diverse evolutionary forces reveals the mosaic nature of selection on genomic regions associated with human preterm birth

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