Increased Placental Cell Senescence and Oxidative Stress in Women with Pre-Eclampsia and Normotensive Post-Term Pregnancies
AuthorsScaife, Paula J.; email: firstname.lastname@example.org
Simpson, Amy; email: email@example.com
Kurlak, Lesia O.; email: firstname.lastname@example.org
Briggs, Louise V.; email: email@example.com
Gardner, David S.; email: David.firstname.lastname@example.org
Broughton Pipkin, Fiona; email: Fiona.email@example.com
Jones, Carolyn J. P.; orcid: 0000-0002-0026-9494; email: firstname.lastname@example.org
Mistry, Hiten D.; orcid: 0000-0003-2564-7348; email: email@example.com
MetadataShow full item record
AbstractUp to 11% of pregnancies extend to post-term with adverse obstetric events linked to pregnancies over 42 weeks. Oxidative stress and senescence (cells stop growing and dividing by irreversibly arresting their cell cycle and gradually ageing) can result in diminished cell function. There are no detailed studies of placental cell senescence markers across a range of gestational ages, although increased levels have been linked to pre-eclampsia before full term. This study aimed to determine placental senescence and oxidative markers across a range of gestational ages in women with uncomplicated pregnancies and those with a diagnosis of pre-eclampsia. Placentae were obtained from 37 women with uncomplicated pregnancies of 37–42 weeks and from 13 cases of pre-eclampsia of 31+2–41+2 weeks. The expression of markers of senescence, oxidative stress, and antioxidant defence (tumour suppressor protein p16INK4a, kinase inhibitor p21, interleukin-6 (IL-6), NADPH oxidase 4 (NOX4), glutathione peroxidases 1, 3, and 4 (GPx1, GPx3, and GPx4), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)) genes was measured (quantitative real-time PCR). Protein abundance of p16INK4a, IL-6, NOX4, 8-hydroxy-2′-deoxy-guanosine (8-OHdG), and PlGF was assessed by immunocytochemistry. Placental NOX4 protein was higher in post-term than term deliveries and further increased by pre-eclampsia (p 0.05 for all). P21 expression was higher in post-term placentae (p = 0.012) and in pre-eclampsia (p = 0.04), compared to term. Placental P16INK4a protein expression was increased post-term, compared to term (p = 0.01). In normotensive women, gestational age at delivery was negatively associated with GPx4 and PlGF (mRNA and protein) (p 0.05 for all), whereas a positive correlation was seen with placental P21, NOX4, and P16INK4a (p 0.05 for all) expression. Markers of placental oxidative stress and senescence appear to increase as gestational age increases, with antioxidant defences diminishing concomitantly. These observations increase our understanding of placental health and may contribute to assessment of the optimal gestational age for delivery.
CitationInternational Journal of Molecular Sciences, volume 22, issue 14, page e7295
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-07-02, pub-electronic 2021-07-07
Publication status: Published
Funder: British Heart Foundation; Grant(s): FS/15/32/31604
Showing items related by title, author, creator and subject.
Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid SequencesChauhan, Veeren M.; orcid: 0000-0002-2067-4630; email: firstname.lastname@example.org; Elsutohy, Mohamed M.; email: email@example.com; McClure, C. Patrick; orcid: 0000-0002-1710-1049; email: firstname.lastname@example.org; Irving, William L.; orcid: 0000-0002-7268-3168; email: email@example.com; Roddis, Neil; email: firstname.lastname@example.org; Aylott, Jonathan W.; email: email@example.com (MDPI, 2021-07-14)Enteroviruses are ubiquitous mammalian pathogens that can produce mild to life-threatening disease. We developed a multimodal, rapid, accurate and economical point-of-care biosensor that can detect nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and oligonucleotides to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral nucleic acid sequence (23 bases), which was identified through in silico screening. Oligonucleotides were designed to demonstrate specific complementarity towards the target enteroviral nucleic acid to produce aggregated gold–oligonucleotide nanoconstructs. The conserved target enteroviral nucleic acid sequence (≥1 × 10−7 M, ≥1.4 × 10−14 g/mL) initiates gold–oligonucleotide nanoconstruct disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow assays that utilise gold–oligonucleotide nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (60 s), and could be interpreted with a bespoke software and hardware electronic interface. We anticipate that our methodology will translate in silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave the way forward in the clinical evaluation of disease and complement existing strategies to overcome antimicrobial resistance.
Selective Inhibition of Heparan Sulphate and Not Chondroitin Sulphate Biosynthesis by a Small, Soluble Competitive InhibitorMaciej-Hulme, Marissa L.; orcid: 0000-0001-5615-4197; email: firstname.lastname@example.org; Dubaissi, Eamon; email: email@example.com; Shao, Chun; email: Chun.Shao@bms.com; Zaia, Joseph; orcid: 0000-0001-9497-8701; email: firstname.lastname@example.org; Amaya, Enrique; orcid: 0000-0002-1805-8548; email: email@example.com; Flitsch, Sabine L.; email: Sabine.Flitsch@manchester.ac.uk; Merry, Catherine L. R.; orcid: 0000-0002-3490-2809; email: firstname.lastname@example.org (MDPI, 2021-06-29)The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds provide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole organisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?Park, JooYong; email: email@example.com; Choi, Ji-Yeob; email: firstname.lastname@example.org; Choi, Jaesung; email: email@example.com; Chung, Seokang; email: firstname.lastname@example.org; Song, Nan; orcid: 0000-0002-9182-1060; email: email@example.com; Park, Sue K.; orcid: 0000-0001-5002-9707; email: firstname.lastname@example.org; Han, Wonshik; email: email@example.com; Noh, Dong-Young; email: firstname.lastname@example.org; Ahn, Sei-Hyun; email: email@example.com; Lee, Jong Won; email: firstname.lastname@example.org; et al. (MDPI, 2021-05-14)In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.