bims-reprim 2022-01-16 papers

Issue of 2022–01–16
four papers selected by
Iva Filipovic, Karolinska Institutet

Sci Rep. 2022 Jan 12. 12(1): 601

The amniotic fluid proteome changes with gestational age in normal pregnancy: a cross-sectional study.

Gaurav Bhatti, Roberto Romero, Nardhy Gomez-Lopez, Tinnakorn Chaiworapongsa, Eunjung Jung, Francesca Gotsch, Roger Pique-Regi, Percy Pacora, Chaur-Dong Hsu, Mahendra Kavdia, Adi L Tarca.

The cell-free transcriptome in amniotic fluid (AF) has been shown to be informative of physiologic and pathologic processes in pregnancy; however, the change in AF proteome with gestational age has mostly been studied by targeted approaches. The objective of this study was to describe the gestational age-dependent changes in the AF proteome during normal pregnancy by using an omics platform. The abundance of 1310 proteins was measured on a high-throughput aptamer-based proteomics platform in AF samples collected from women during midtrimester (16-24 weeks of gestation, n = 15) and at term without labor (37-42 weeks of gestation, n = 13). Only pregnancies without obstetrical complications were included in the study. Almost 25% (320) of AF proteins significantly changed in abundance between the midtrimester and term gestation. Of these, 154 (48.1%) proteins increased, and 166 (51.9%) decreased in abundance at term compared to midtrimester. Tissue-specific signatures of the trachea, salivary glands, brain regions, and immune system were increased while those of the gestational tissues (uterus, placenta, and ovary), cardiac myocytes, and fetal liver were decreased at term compared to midtrimester. The changes in AF protein abundance were correlated with those previously reported in the cell-free AF transcriptome. Intersecting gestational age-modulated AF proteins and their corresponding mRNAs previously reported in the maternal blood identified neutrophil-related protein/mRNA pairs that were modulated in the same direction. The first study to utilize an aptamer-based assay to profile the AF proteome modulation with gestational age, it reveals that almost one-quarter of the proteins are modulated as gestation advances, which is more than twice the fraction of altered plasma proteins (~ 10%). The results reported herein have implications for future studies focused on discovering biomarkers to predict, monitor, and diagnose obstetrical diseases.

DOI: https://doi.org/10.1038/s41598-021-04050-9

Proteomics. 2022 Jan 11. e2100227

Elucidation of the protein composition of mouse seminal vesicle fluid.

Shannon P Smyth, Brett Nixon, Amanda L Anderson, Heather C Murray, Jacinta H Martin, Lily A MacDougall, Sarah A Robertson, David A Skerrett-Byrne, John E Schjenken.

The seminal vesicles are male accessory sex glands that contribute the major portion of the seminal plasma in which mammalian spermatozoa are bathed during ejaculation. In addition to conveying sperm through the ejaculatory duct, seminal vesicle secretions support sperm survival after ejaculation, and influence the female reproductive tract to promote receptivity to pregnancy. Analysis of seminal vesicle fluid (SVF) composition by proteomics has proven challenging, due to its highly biased protein signature with a small subset of dominant proteins and the difficulty of solubilizing this viscous fluid. As such, publicly available proteomics datasets identify only 85 SVF proteins in total. To address this limitation, we report new a preparative methodology involving sequential solubilization of mouse SVF in guanidine hydrochloride, acetone precipitation, and analysis by label-free mass spectrometry. Using this strategy, we identified 126 SVF proteins, including 83 previously undetected in SVF. Members of the seminal vesicle secretory protein family were the most abundant, accounting for 79% of all peptide spectrum matches. Functional analysis identified inflammation and formation of the vaginal plug as the two most prominent biological processes. Other notable processes included modulation of sperm function and regulation of the female reproductive tract immune environment. Together, these findings provide a robust methodological framework for future SVF studies and identify novel proteins with potential to influence both male and female reproductive physiology. This article is protected by copyright. All rights reserved.

Keywords: bioinformatics; proteomics; seminal vesicle fluid

DOI: https://doi.org/10.1002/pmic.202100227

J Matern Fetal Neonatal Med. 2022 Jan 10. 1-6

Concentration of vaginal and systemic cytokines obtained early in pregnancy and their impact on preterm birth.

Christopher Nold, Anastasia Barros, Caroline Rogi, Carsen Sulzer, Angela Quental, Sarah Reid, Mohaned Serdah, Anthony T Vella.

OBJECTIVE: A number of factors can lead to a maternal pro-inflammatory response resulting in a spontaneous preterm birth. However, it remains unknown if an upregulation in the maternal immune system early in pregnancy leads to an increase in pro-inflammatory cytokines and ultimately preterm birth. Therefore, we hypothesize an increase in vaginal and systemic pro-inflammatory cytokines early pregnancy is associated with an increased risk of preterm birth.
STUDY DESIGN: Patients initiating prenatal care prior to 14 weeks gestation were recruited for eligibility. A vaginal swab and serum sample was obtained at the first prenatal visit and these were then stored at -80 C. Patients were then followed for their gestational age at delivery. Five patients delivering preterm (cases) were matched with ten patients delivering at term (controls) based on age, BMI, smoking status and ethnicity. The serum and vaginal swabs from the cases and controls were then analyzed for the following cytokines using a multiplex cytokine assay: GM-CSF, IL-1b, IL-6, TNFα, and Rantes.
RESULTS: A total of 116 patients were screened for eligibility and 96 of these patients had samples obtained prior to 14 weeks gestation. Of these 96, 5 had a spontaneous preterm birth and these were matched to 10 controls. There was no difference detected in the cytokine concentrations of GM-CSF, IL-1b, IL-6, TNFα, and Rantes in the serum or cervicovaginal fluid between cases and controls.
CONCLUSION: This study demonstrates there is no difference in cytokine concentrations of several pro-inflammatory cytokines in the vagina or in the serum prior to 14 weeks gestation in patients delivering preterm. Therefore, the concentration of the cytokines analyzed in this study from the vagina and serum have little predictive value on the risk of preterm birth. Further research is needed to deepen our understanding of the mechanisms leading to preterm birth.

Keywords: Preterm birth; cytokines; inflammation

DOI: https://doi.org/10.1080/14767058.2022.2026916

Reproduction. 2022 Jan 01. pii: REP-21-0390.R1. [Epub ahead of print]

Pregnancy-specific glycoproteins: evolution, expression, functions, and disease associations.

Tom Moore, John M Williams, Maria Angeles Becerra-Rodriguez, Matthew Dunne, Robert Kammerer, Gabriela Dveksler.

Pregnancy-specific glycoproteins (PSGs) are members of the immunoglobulin superfamily and are closely related to the predominantly membrane-bound CEACAM proteins. PSGs are produced by placental trophoblasts and secreted into the maternal bloodstream at high levels where they may regulate maternal immune and vascular functions through receptor binding and modulation of cytokine and chemokine expression and activity. PSGs may have autocrine and paracrine functions in the placental bed, and PSGs can activate soluble and extracellular matrix bound TGF-β, with potentially diverse effects on multiple cell types. PSGs are also found at high levels in the maternal circulation, at least in human, where they may have endocrine functions. In a non-reproductive context, PSGs are expressed in the gastrointestinal tract and their deregulation may be associated with colorectal cancer and other diseases. Like many placental hormones, PSGs are encoded by multigene families and they have an unusual phylogenetic distribution, being found predominantly in species with hemochorial placentation, with the notable exception of the horse in which PSG-like proteins are expressed in the endometrial cups of the epitheliochorial placenta. The evolution and expansion of PSG gene families appears to be a highly active process, with significant changes in gene numbers and protein domain structures in different mammalian lineages, and reports of extensive copy number variation at the human locus. Against this apparent diversification, the available evidence indicates extensive conservation of PSG functions in multiple species. These observations are consistent with maternal-fetal conflict underpinning the evolution of PSGs.

DOI: https://doi.org/10.1530/REP-21-0390