Uterine serpin (<scp>SERPINA</scp> 14) correlates negatively with cytokine production at the foetal–maternal interface but not in the corpus luteum in pregnant dairy heifers experimentally infected with <i>Neospora caninum</i>

Serrano-Pérez, B.; Almerı́a, S.; Mur-Novales, R.; López-Helguera, I.; García-Ispierto, Irina; Alabart, J. L.; Darwich, Laila; López‐Gatius, F.

doi:10.1111/rda.12937

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…Neutrophil elastase in cervical secretions has been proposed to predict premature delivery [ 30 ]. In addition to protease inhibition, SERPINA1 family members prevent collagen breakdown, which triggers hypoxia [ 31 ]. Low serum levels of AAT are associated with spontaneous abortion and elevated proinflammatory cytokines [ 21 ], and SERPINA3 is a potential preeclampsia marker [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Human placental proteomics and exon variant studies link AAT/SERPINA1 with spontaneous preterm birth

Tiensuu

Haapalainen

Tissarinen

et al. 2022

BMC Med

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Background Preterm birth is defined as live birth before 37 completed weeks of pregnancy, and it is a major problem worldwide. The molecular mechanisms that lead to onset of spontaneous preterm birth are incompletely understood. Prediction and evaluation of the risk of preterm birth is challenging as there is a lack of accurate biomarkers. In this study, our aim was to identify placental proteins that associate with spontaneous preterm birth. Methods We analyzed the proteomes from placentas to identify proteins that associate with both gestational age and spontaneous labor. Next, rare and potentially damaging gene variants of the identified protein candidates were sought for from our whole exome sequencing data. Further experiments we performed on placental samples and placenta-associated cells to explore the location and function of the spontaneous preterm labor-associated proteins in placentas. Results Exome sequencing data revealed rare damaging variants in SERPINA1 in families with recurrent spontaneous preterm deliveries. Protein and mRNA levels of alpha-1 antitrypsin/SERPINA1 from the maternal side of the placenta were downregulated in spontaneous preterm births. Alpha-1 antitrypsin was expressed by villous trophoblasts in the placenta, and immunoelectron microscopy showed localization in decidual fibrinoid deposits in association with specific extracellular proteins. siRNA knockdown in trophoblast-derived HTR8/SVneo cells revealed that SERPINA1 had a marked effect on regulation of the actin cytoskeleton pathway, Slit–Robo signaling, and extracellular matrix organization. Conclusions Alpha-1 antitrypsin is a protease inhibitor. We propose that loss of the protease inhibition effects of alpha-1 antitrypsin renders structures critical to maintaining pregnancy susceptible to proteases and inflammatory activation. This may lead to spontaneous premature birth.

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Section: Introductionmentioning

confidence: 99%

Human placental proteomics and exon variant studies link AAT/SERPINA1 with spontaneous preterm birth

Tiensuu

Haapalainen

Tissarinen

et al. 2022

BMC Med

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“…It indicates changes in the metabolic pathways of protein degradation occurring during PE. In addition, family members of SERPINA1 prevent collagen breakdown, which triggers hypoxia [27]. In the culture of trophoblast cells under hypoxia, there is an increase in the expression of the SERPINA1 gene by three times [28].…”

Section: Discussionmentioning

confidence: 99%

SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity

Стародубцева

Nizyaeva

Baev

et al. 2020

IJMS

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Preeclampsia (PE) is a multisystem disorder associated with pregnancy and its frequency varies from 5 to 20 percent of pregnancies. Although a number of preeclampsia studies have been carried out, there is no consensus about disease etiology and pathogenesis so far. Peptides of SERPINA1 (α1-antitrypsin) in urine remain one of the most promising peptide markers of PE. In this study the diagnostic potential of urinary α1-antitrypsin peptides in PE was evaluated. The urinary peptidome composition of 79 pregnant women with preeclampsia (PE), chronic arterial hypertension (CAH), and a control group was investigated. Mann–Whitney U-test (p < 0.05) revealed seven PE specific SERPINA1 peptides demonstrating 52% sensitivity and 100% specificity. SERPINA1 in urine has been associated with the most severe forms of preeclampsia (p = 0.014), in terms of systolic hypertension (p = 0.01) and proteinuria (p = 0.006). According to Spearman correlation analysis, the normalized intensity of SERPINA1 urinary peptides has a similar diagnostic pattern with known diagnostic PE markers, such as sFLT/PLGF. SERPINA1 peptides were not urinary excreted in superimposed PE (PE with CAH), which is a milder form of PE. An increase in expression of SERPINA1 in the structural elements of the placenta during preeclampsia reflects a protective mechanism against hypoxia. Increased synthesis of SERPINA1 in the trophoblast leads to protein accumulation in fibrinoid deposits. It may block syncytial knots and placenta villi, decreasing trophoblast invasion. Excretion of PE specific SERPINA1 peptides is associated with syncytiotrophoblast membrane destruction degradation and increased SERPINA1 staining. It confirms that the placenta could be the origin of SERPINA1 peptides in urine. Significant correlation (p < 0.05) of SERPINA1 expression in syncytiotrophoblast membrane and cytoplasm with the main clinical parameters of severe PE proves the role of SERPINA1 in PE pathogenesis. Estimation of SERPINA1 peptides in urine can be used as a diagnostic test of the severity of the condition to determine further treatment, particularly the need for urgent surgical delivery.

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“…N. caninum infection in cattle has been associated with a decrease in SERPINA14 levels in pregnant cows resulting in abortion. SERPINA14 has a regulatory decrease of the immunosuppressive effect of progesterone in cases of pregnancy [201,202]. Although there is an unknown immunological role, host factors such as neurotropic proteins in rat tissues [203], cholesterol and lipoproteins in human and bovine cell lines [204], purine, acetylcholinesterase and butyrylcholinesterase in gerbil tissues and blood [205,206] seem to play a role in N. caninum infection in mentioned hosts because of marked altered levels among infected and non-infected hosts.…”

Section: Dendritic Cells and Macrophagesmentioning

confidence: 99%

From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts

Fereig

Nishikawa

2020

Pathogens

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Neospora caninum is an intracellular protozoan parasite affecting numerous animal species. It induces significant economic losses because of abortion and neonatal abnormalities in cattle. In case of infection, the parasite secretes numerous arsenals to establish a successful infection in the host cell. In the same context but for a different purpose, the host resorts to different strategies to eliminate the invading parasite. During this battle, numerous key factors from both parasite and host sides are produced and interact for the maintaining and vanishing of the infection, respectively. Although several reviews have highlighted the role of different compartments of the immune system against N. caninum infection, each one of them has mostly targeted specific points related to the immune component and animal host. Thus, in the current review, we will focus on effector molecules derived from the host cell or the parasite using a comprehensive survey method from previous reports. According to our knowledge, this is the first review that highlights and discusses immune response at the host cell–parasite molecular interface against N. caninum infection in different susceptible hosts.

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Uterine serpin (SERPINA 14) correlates negatively with cytokine production at the foetal–maternal interface but not in the corpus luteum in pregnant dairy heifers experimentally infected with Neospora caninum

Cited by 6 publications

References 10 publications

Human placental proteomics and exon variant studies link AAT/SERPINA1 with spontaneous preterm birth

Human placental proteomics and exon variant studies link AAT/SERPINA1 with spontaneous preterm birth

SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity

From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts

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