The cytotrophoblast of human placenta transitions into an outer multinucleated syncytiotrophoblast (STB) layer that covers chorionic villi which are in contact with maternal blood in the intervillous space. During pregnancy, the Zika virus (ZIKV) poses a serious prenatal threat. STB cells are resistant to ZIKV infections, yet placental cells within the mesenchyme of chorionic villi are targets of ZIKV infection. We seek to determine whether ZIKV can open the paracellular pathway of STB cells. This route is regulated by tight junctions (TJs) which are present in the uppermost portion of the lateral membranes of STB cells. We analyzed the paracellular permeability and expression of E-cadherin, occludin, JAMs –B and –C, claudins -1, -3, -4, -5 and -7, and ZO-1, and ZO-2 in the STB of placentae from ZIKV-infected and non-infected women. In ZIKV-infected placentae, the pattern of expression of TJ proteins was preserved, but the amount of claudin-4 diminished. Placentae from ZIKV-infected women were permeable to ruthenium red, and had chorionic villi with a higher mean diameter and Hofbauer hyperplasia. Finally, ZIKV added to the basolateral surface of a trophoblast cell line reduced the transepithelial electrical resistance. These results suggest that ZIKV can open the paracellular pathway of STB cells.
Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributors to perinatal morbidity and mortality. These pregnancy disorders are associated with placental dysfunction and share similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lncRNAs from pregnant women from four study groups: PE, IUGR, PE-IUGR, and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP (n = 461; 314 mRNAs: 252 up-regulated and 62 down-regulated; 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP (n = 39), including 9 lncRNAs with a high correlation degree (p < 0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification, and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of PE and IUGR.
Controversy remains surrounding vitamin D routine supplementation in healthy pregnancy, and the doses are unclear. The aim of this study was to describe maternal vitamin D status throughout pregnancy in a group of Mexican women and evaluate the effect of frequently prescribed doses of vitamin D3 on longitudinal 25-OH-D concentrations, adjusting for obesity, season, and other factors. We conducted a cohort study (Instituto Nacional de Perinatología-INPer) (2017–2020)) of healthy pregnant women without complications. Pregestational overweight/obesity (body mass index ≥ 25), vitamin D3 supplementation (prescribed by physician; 0–250, 250–400, and >400 IU/day), and serum 25-OH-D concentrations (ELISA) were evaluated in each trimester of pregnancy. Vitamin D deficiency or insufficiency was computed (<20 and <30 ng/mL, respectively). We studied 141 adult women; 58.5% had pregestational obesity or overweight. In the first trimester, 45.8% of the women were supplemented with vitamin D3; 51.4% had vitamin D insufficiency and 37.3%, deficiency. In the third trimester, 75.4% of the women were supplemented, and 20% of them still had deficiency. The final general mixed linear model showed that 25-OH-D significantly increased throughout pregnancy (p < 0.001); the highest increase was observed in the third trimester in women with doses >400 IU/day of vitamin D3 (+4 ng/mL, 95% CI: 1.72–8.11 ng/mL). In winter/autumn, 25-OH-D concentrations were also lower (p ≤ 0.05). In this group of pregnant Mexican women, the prevalence of vitamin D deficiency and insufficiency was high. A higher increase in 25-OH-D concentrations during pregnancy was observed when the women were supplemented with >400 IU/day. Common supplementation doses of 250–400 IU/day were insufficient for achieving an adequate maternal vitamin D status.
In this work, a novel multimodal learning approach for early prediction of birth weight is presented. Fetal weight is one of the most relevant indicators in the assessment of fetal health status. The aim is to predict early birth weight using multimodal maternal–fetal variables from the first trimester of gestation (Anthropometric data, as well as metrics obtained from Fetal Biometry, Doppler and Maternal Ultrasound). The proposed methodology starts with the optimal selection of a subset of multimodal features using an ensemble-based approach of feature selectors. Subsequently, the selected variables feed the nonparametric Multiple Kernel Learning regression algorithm. At this stage, a set of kernels is selected and weighted to maximize performance in birth weight prediction. The proposed methodology is validated and compared with other computational learning algorithms reported in the state of the art. The obtained results (absolute error of 234 g) suggest that the proposed methodology can be useful as a tool for the early evaluation and monitoring of fetal health status through indicators such as birth weight.
Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2′-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R2 = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2′-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.
Adolescent pregnancy is a significant public health concern, with maternal and fetal risks compounded by pregnancy-related anatomical, hormonal, and urinary changes that predispose to urinary tract infections (UTIs). Alterations in the urinary microbiome may further influence infection susceptibility, yet little is known about its role during adolescent pregnancy. This study analyzed the urinary microbiome of adolescent pregnant patients and its association with UTI and recurrent UTI (rUTI) across gestation. Healthy adolescents were enrolled in the first trimester and followed through subsequent trimesters, with urine samples collected at each visit for microbiological diagnosis. Patients were classified as healthy (34 samples), single UTI (22 samples), or rUTI (31 samples), and oxford-nanopore 16S rRNA sequencing was used to assess taxonomic composition, microbial diversity, and operational taxonomic units. Distinct trimester-specific patterns were observed, with Lactobacillus iners progressively increasing and L. kitasatonis emerging as a dominant taxon during adolescent pregnancy. Interestingly, rUTI cases showed persistent E. coli, reduced L. kitasatonis and L. ultunensis in the second trimester, and the appearance of Fannyhessea vaginae (Atopobium vaginae) in the third. These findings suggest a potential microbial signature of rUTI in adolescent pregnancy, underscoring the need for personalized preventive strategies and the establishment of microbiome-based clinical cutoffs.