Sex differences in DNA methylation across gestation: a large scale, cross-cohort, multi-tissue analysis.

Biological sex is a key variable influencing many physiological systems. Disease prevalence as well as treatment success can be modified by sex. Differences emerge already early in life and include pregnancy complications and adverse birth outcomes. The placenta is a critical organ for fetal development and shows sex-based differences in the expression of hormones and cytokines. Epigenetic regulation, such as DNA methylation (DNAm), may underlie the previously reported placental sexual dimorphism. We associated placental DNAm with fetal sex in three cohorts. Individual cohort results were meta-analyzed with random-effects modelling. CpG-sites differentially methylated with sex were further investigated regarding pathway enrichment, overlap with methylation quantitative trait loci (meQTLs), and hits from phenome-wide association studies (PheWAS). We evaluated the consistency of findings across tissues (CVS, i.e. chorionic villus sampling from early placenta, and cord blood) as well as with gene expression. We identified 10,320 epigenome-wide significant sex-differentially methylated probes (DMPs) spread throughout the epigenome of the placenta at birth. Most DMPs presented with lower DNAm levels in females. DMPs mapped to genes upregulated in brain, were enriched for neurodevelopmental pathways and significantly overlapped with meQTLs and PheWAS hits. Effect sizes were moderately correlated between CVS and placenta at birth, but only weakly correlated between birth placenta and cord blood. Sex differential gene expression in birth placenta was less pronounced and implicated genetic regions only marginally overlapped with those associated with differential DNAm. Our study provides an integrative perspective on sex-differential DNAm in perinatal tissues underscoring the possible link between placenta and brain.

Placental metastasis from maternal NUT carcinoma: diagnostic pitfalls and challenges.

We report a young pregnant woman with large midline thoracic mass and markedly elevated serum alpha-fetoprotein (AFP) levels. Initially suspected as a germ cell tumour (GCT) due to age, site, and high AFP levels, a biopsy unveiled a high-grade malignant tumour characterised by undifferentiated monotonous cells. Although tumour cells exhibited positive AFP, the overall immunoprofile did not provide additional evidence to support GCT. Further work-up showed positive for NUT (nuclear protein in testis) immunostaining and the presence of BRD4-NUT1 fusion, confirming the diagnosis of NUT carcinoma. On radiology, there were extensive metastases to lungs, liver, vertebrae, and placenta. Despite aggressive chemotherapy, radiotherapy and immunotherapy, she did not respond to the therapies. Fortunately, her child was not affected by the carcinoma. This is the first case highlighting that thoracic lung primary NUT carcinoma can spread to the placenta and manifest with elevated serum AFP levels, potentially leading to misdiagnosis as GCT both clinically and pathologically.

Prospective study of malaria in pregnancy, placental and congenital malaria in Northwest Colombia.

BACKGROUND: Pregnancy Associated Malaria (PAM) include malaria in pregnancy (MiP), placental malaria (PM), and congenital malaria (CM). The evidence available in Colombia on PAM focuses on one of the presentations (MiP, PM or CM), and no study longitudinally analyses the infection from the pregnant woman, passing through the placenta, until culminating in the newborn. This study determined the frequency of MiP, PM, and CM caused by Plasmodium vivax, Plasmodium falciparum, or mixed infections, according to Thick Blood Smear (TBS) and quantitative Polymerase Chain Reaction (qPCR). Identifying associated factors of PAM and clinical-epidemiological outcomes in northwestern Colombia. METHODS: Prospective study of 431 pregnant women, their placenta, and newborns registered in the data bank of the research Group "Salud y Comunidad César Uribe Piedrahíta" which collected information between 2014 and 2020 in endemic municipalities of the departments of Córdoba and Antioquia. The frequency of infection was determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Student t-test, prevalence ratios, and control for confounding variables by log-binomial regression. RESULTS: The frequency of MiP was 22.3% (4.6% using TBS), PM 24.8% (1.4% using TBS), and CM 11.8% (0% using TBS). Using TBS predominated P. vivax. Using qPCR the proportions of P. vivax and P. falciparum were similar for MiP and PM, but P. falciparum predominated in CM. The frequency was higher in nulliparous, and women with previous malaria. The main clinical effects of PAM were anaemia, low birth weight, and abnormal APGAR score. CONCLUSIONS: The magnitude of infections was not detected with TBS because most cases were submicroscopic (TBS-negative, qPCR-positive). This confirmed the importance of improving the molecular detection of cases. PAM continue being underestimated in the country due to that in Colombia the control programme is based on TBS, despite its outcomes on maternal, and congenital health.

Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report.

BACKGROUND: Intrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management. CASE PRESENTATION: We report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells. CONCLUSION: This case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

The relationship between cervical length and area measurements evaluated by MRI and the amount of hemorrhage in PAS cases.

BACKGROUND: Placenta accreta spectrum often leads to massive hemorrhage and even maternal shock and death. This study aims to identify whether cervical length and cervical area measured by magnetic resonance imaging correlate with massive hemorrhage in patients with placenta accreta spectrum. METHODS: The study was conducted at our hospital, and 158 placenta previa patients with placenta accreta spectrum underwent preoperative magnetic resonance imaging examination were included. The cervical length and cervical area were measured and evaluated their ability to identify massive hemorrhage in patients with placenta accreta spectrum. RESULTS: The cervical length and area in patients with massive hemorrhage were both significantly smaller than those in patients without massive hemorrhage. The results of multivariate analysis show that cervical length and cervical area were significantly associated with massive hemorrhage. In all patients, a negative linear was found between cervical length and amount of blood loss (r =-0.613), and between cervical area and amount of blood loss (r =-0.629). Combined with cervical length and cervical area, the sensitivity, specificity, and the area under the curve for the predictive massive hemorrhage were 88.618%, 90.209%, and 0.890, respectively. CONCLUSION: The cervical length and area might be used to recognize massive hemorrhage in placenta previa patients with placenta accreta spectrum.

Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator-activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.

The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions.

CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside of a CD4+ T cells and with the Src kinase, LCK, on the inside. Previously, we reported that the CD4 transmembrane GGXXG and cytoplasmic juxtamembrane (C/F)CV+C motifs found in eutherian (placental mammal) CD4 have constituent residues that evolved under purifying selection (Lee et al., 2022). Expressing mutants of these motifs together in T cell hybridomas increased CD4-LCK association but reduced CD3ζ, ZAP70, and PLCγ1 phosphorylation levels, as well as IL-2 production, in response to agonist pMHCII. Because these mutants preferentially localized CD4-LCK pairs to non-raft membrane fractions, one explanation for our results was that they impaired proximal signaling by sequestering LCK away from TCR-CD3. An alternative hypothesis is that the mutations directly impacted signaling because the motifs normally play an LCK-independent role in signaling. The goal of this study was to discriminate between these possibilities. Using T cell hybridomas, our results indicate that: intracellular CD4-LCK interactions are not necessary for pMHCII-specific signal initiation; the GGXXG and (C/F)CV+C motifs are key determinants of CD4-mediated pMHCII-specific signal amplification; the GGXXG and (C/F)CV+C motifs exert their functions independently of direct CD4-LCK association. These data provide a mechanistic explanation for why residues within these motifs are under purifying selection in jawed vertebrates. The results are also important to consider for biomimetic engineering of synthetic receptors.

RNA-seq analysis-based study on the effects of gestational diabetes mellitus on macrosomia.

Background: Both the mother and the infant are negatively impacted by macrosomia. Macrosomia is three times as common in hyperglycemic mothers as in normal mothers. This study sought to determine why hyperglycemic mothers experienced higher macrosomia. Methods: Hematoxylin and Eosin staining was used to detect the placental structure of normal mother(NN), mothers who gave birth to macrosomia(NM), and mothers who gave birth to macrosomia and had hyperglycemia (DM). The gene expressions of different groups were detected by RNA-seq. The differentially expressed genes (DEGs) were screened with DESeq2 R software and verified by qRT-PCR. The STRING database was used to build protein-protein interaction networks of DEGs. The Cytoscape was used to screen the Hub genes of the different group. Results: The NN group's placental weight differed significantly from that of the other groups. The structure of NN group's placenta is different from that of the other group, too. 614 and 3207 DEGs of NM and DM, respectively, were examined in comparison to the NN group. Additionally, 394 DEGs of DM were examined in comparison to NM. qRT-PCR verified the results of RNA-seq. Nucleolar stress appears to be an important factor in macrosomia, according on the results of KEGG and GO analyses. The results revealed 74 overlapped DEGs that acted as links between hyperglycemia and macrosomia, and 10 of these, known as Hub genes, were key players in this process. Additionally, this analysis believes that due of their close connections, non-overlapping Hubs shouldn't be discounted. Conclusion: In diabetic mother, ten Hub genes (RPL36, RPS29, RPL8 and so on) are key factors in the increased macrosomia in hyperglycemia. Hyperglycemia and macrosomia are linked by 74 overlapping DEGs. Additionally, this approach contends that non-overlapping Hubs shouldn't be ignored because of their tight relationships.

The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns.

Introduction: Inflammation of the placenta is harmful to both the fetus and the mother. Inflammation is strongly associated with diabetes, a common complication of pregnancy. Hofbauer cells (HBCs), unique immune system cells of fetal origin in the placenta, play complex roles, including growth of placental villi and their branching, stromal remodelling, and angiogenesis. Methods: Our study investigated the expression of IL-1ß, IL-10, CYP2C8, CYP2C9, CYP2J2 and sEH in HBCs from patients with type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM) compared to healthy controls using immunohistochemistry. We also assessed the structure of the villus stroma using Masson´s trichrome. Results: In T1DM, HBCs showed inflammatory activation characterised by increased IL-1ß and decreased CYP epoxygenase expression compared to normal placentas. Conversely, significant inflammation in HBCs appeared less likely in GDM, as levels of IL-1ß and CYP epoxygenases remained stable compared to normal placentas. However, GDM showed a significant increase in sEH expression. Both types of diabetes showed delayed placental villous maturation and hypovascularisation, with GDM showing a more pronounced effect. Conclusion: The expression profiles of IL-1ß, CYP epoxygenases and sEH significantlly differ between controls and diabetic placentas and between T1DM and GDM. These facts suggest an association of the CYP epoxygenase-EETs-sEH axis with IL-1ß expression as well as villous stromal hypovascularisation. Given the stable high expression of IL-10 in both controls and both types of diabetes, it appears that immune tolerance is maintained in HBCs.

Intra-horn insemination in the alpaca Vicugna pacos: Copulatory wounding and deep sperm deposition.

Alpacas (Vicugna pacos) are reported to be the rare mammal in which the penis enters the uterus in mating. To date, however, only circumstantial evidence supports this assertion. Using female alpacas culled for meat, we determined that the alpaca penis penetrates to the very tips of the uterine horns, abrading the tract and breaking fine blood vessels. All female alpacas sacrificed one hour or 24 hours after mating showed conspicuous bleeding in the epithelium of some region of their reproductive tract, including the hymen, cervix and the tips of each uterine horn, but typically not in the vagina. Unmated females showed no evidence of conspicuous bleeding. Histological examination of mated females revealed widespread abrasion of the cervical and endometrial epithelium, injuries absent in unmated females. Within one hour of mating, sperm were already present in the oviduct. The male alpaca's cartilaginous penis tip with a hardened urethral process is likely responsible for the copulatory abrasion. The entire female reproductive tract interacts with the penis, functioning like a vagina. Alpacas are induced ovulators, and wounding may hasten delivery of the seminal ovulation-inducing factor beta-NGF into the female's blood stream. There is no evidence of sexual conflict in copulation in alpaca, and thus wounding may also be one of a variety of mechanisms devised by mammals to induce a beneficial, short-term inflammatory response that stimulates blastocyst implantation, the uterine remodeling associated with placental development, and thus the success of early pregnancy.

Utah flouts FDA with new placental stem cell law.

Measure declares that patients can be given unapproved treatments.

Causes and Effects of COVID-19 Vaccine Hesitancy Among Pregnant Women and its Association with Adverse Maternal, Placental, and Perinatal Outcomes.

Populations identified to be severely affected by COVID-19, such as pregnant patients, require special consideration in vaccine counseling, access, and provider education. Maternal infection with COVID-19 poses a significant risk to the maternal-fetal dyad with known adverse placenta destruction [1-5]. Despite the widespread access and availability of vaccinations, vaccine hesitancy continues to persist and is highly prevalent in pregnant populations [6-9]. Addressing the multitude of social ecological factors surrounding vaccine hesitancy can aid in providing holistic counseling [10]. However, such factors are foremost shaped by maternal concern over possible fetal effects from vaccination. While changes in policy can help foster vaccine access and acceptance, increasing global provider education and incorporation of motivational interviewing skills are the first steps towards increasing maternal acceptance.

Efficacy and safety of prophylactic balloon occlusion in the management of placenta accreta spectrum disorder: a retrospective cohort study.

OBJECTIVE: Placenta accreta spectrum disorder (PAS) is a serious obstetric complication associated with significant maternal morbidity and mortality. Prophylactic balloon occlusion (PBO), as an intravascular interventional therapies, has emerged as a potential management strategy for controlling massive hemorrhage in patients with PAS. However, current evidence about the clinical application of PBO in PAS patients are still controversial. This study aimed to evaluate the effectiveness and safety of PBO in the management of PAS. METHODS: A retrospective cohort study including PAS patients underwent cesarean delivery was conducted in a tertiary hospital from January 2015 to March 2022. Included PAS patients were further divided into balloon and control groups by whether PBO was performed. Groups were compared for demographic characteristics, intraoperative and postoperative parameters, maternal and neonatal outcomes, PBO-related complication and follow up outcomes. Additionally, multivariate-logistic regression analysis was performed to determine the definitive associations between PBO and risk of massive hemorrhage and hysterectomy. RESULTS: A total of 285 PAS patients met the inclusion criteria were included, of which 57 PAS patients underwent PBO (PBO group) and 228 women performed cesarean section (CS) without PBO (control group). Irrespective of the differences of baseline characteristics between the two groups, PBO intervention did not reduce the blood loss, hysterectomy rate and postoperative hospital stay, but it prolonged the operation time and increased the cost of hospitalization (All P < 0.05) Additionally, there were no significant differences in postoperative complications, neonatal outcomes, and follow-up outcomes(All P > 0.05). In particular, patients undergoing PBO were more likely to develop the venous thrombosis postoperatively (P = 0.001). However, multivariate logistic regression analysis showed that PBO significantly decreased the risk of massive hemorrhage (OR 0.289, 95%CI:0.109-0.766, P = 0.013). The grade of PAS and MRI with S2 invasion were the significant risk factors affecting massive hemorrhage(OR:6.232 and OR:5.380, P<0.001). CONCLUSION: PBO has the potential to reduce massive hemorrhage in PAS patients undergoing CS. Obstetricians should, however, be aware of potential complications arising from the PBO. Additionally, MRI with S2 invasion and PAS grade will be useful to identify PAS patients who at high risk and may benefit from PBO. In brief, PBO seem to be a promising alternative for management of PAS, yet well-designed randomized controlled trials are needed to convincingly demonstrate its benefits and triage the necessity of PBO.

[Genetic origin analysis of regions of homozygosity in three cases].

OBJECTIVE: To explore the genetic characteristics of three fetuses with regions of homozygosity (ROH). METHODS: Three fetuses with ROH diagnosed at Nanjing Drum Tower Hospital on December 2, 2020, March 19, 2021, and May 27, 2022, respectively were selected as the study subjects. Clinical data of the fetuses were collected. Chromosomal microarray analysis (CMA) was used to detect the ROH, and tandem repeat sequences (STR)-based multiplex PCR assay was used to identify the mosaicism status in fetus 1. RESULTS: Partial maternal isodisomy (iUPD) (16) was found in fetus 1, for which trisomy rescue may be accountable. Meanwhile, the fetus also has confined placental mosaicism (CPM) but not true mosaicism. The formation mechanism of ROH for fetus 2 was identity by descent. Partial maternal iUPD (7) was found in fetus 3, which may be due to gametic recombination. CONCLUSION: The ROH of the three fetuses were inherited from both parents or the mother. Above findings suggested that it is justified to detect ROH on imprinting disorder-related chromosomes when potential uniparental disomy is suspected.

Characteristics and treatment for severe postpartum haemorrhage in different midwifery hospitals in one district of Beijing in China: an institution-based, retrospective cohort study.

OBJECTIVE: To identify the characteristics and treatment approaches for patients with severe postpartum haemorrhage (SPPH) in various midwifery institutions in one district in Beijing, especially those without identifiable antenatal PPH high-risk factors, to improve regional SPPH rescue capacity. DESIGN: Retrospective cohort study. SETTING: This study was conducted at 9 tertiary-level hospitals and 10 secondary-level hospitals in Haidian district of Beijing from January 2019 to December 2022. PARTICIPANTS: The major inclusion criterion was SPPH with blood loss ≥1500 mL or needing a packed blood product transfusion ≥1000 mL within 24 hours after birth. A total of 324 mothers with SPPH were reported to the Regional Obstetric Quality Control Office from 19 midwifery hospitals. OUTCOME MEASURES: The pregnancy characteristics collected included age at delivery, gestational weeks at delivery, height, parity, delivery mode, antenatal PPH high-risk factors, aetiology of PPH, bleeding amount, PPH complications, transfusion volume and PPH management. SPPH characteristics were compared between two levels of midwifery hospitals and their association with antenatal PPH high-risk factors was determined. RESULTS: SPPH was observed in 324 mothers out of 106 697 mothers in the 4 years. There were 74.4% and 23.9% cases of SPPH without detectable antenatal PPH high-risk factors in secondary and tertiary midwifery hospitals, respectively. Primary uterine atony was the leading cause of SPPH in secondary midwifery hospitals, whereas placental-associated disorders were the leading causes in tertiary institutions. Rates of red blood cell transfusion over 10 units, unscheduled returns to the operating room and adverse PPH complications were higher in patients without antenatal PPH high-risk factors. Secondary hospitals had significantly higher rates of trauma compared with tertiary institutions. CONCLUSION: Examining SPPH cases at various institutional levels offers a more comprehensive view of regional SPPH management and enhances targeted training in this area.

Placental ontogeny in the Yucca Night Lizard, Xantusia vigilis.

Squamate placentas support physiological exchange between mothers and embryos. Uterine and embryonic epithelial cells provide sites for transporting mechanisms and extraembryonic membranes provide the scaffolding for embryonic epithelial cells and vascular systems. Diversity in placental structure involves variation in extraembryonic membrane development as well as epithelial cell specializations. Variation in placental ontogeny is known to occur and, although lineage specific patterns have been described, phylogenetic distribution of specific patterns is poorly understood. Xantusia vigilis is a viviparous lizard in a monophyletic clade, Xantusiidae, of predominantly viviparous species. Xantusiidae is one of two viviparous lineages within the clade Scincoidea that provides an important outgroup comparison for Scincidae, which includes the largest number of independent origins of viviparity among Squamata. Previous reports contain brief descriptions of placental structure of X vigilis but the developmental pattern is unknown including relevant details for comparison with skinks. We studied placental ontogeny in X. vigilis to address two hypotheses: (1) the pattern of development of placental architecture is similar to species of Scincidae and, (2) placental epithelial cell specializations are similar to species of Scincidae. The terminal placental stage of X. vigilis is similar to skinks in that it includes a chorioallantoic placenta and an omphaloplacenta. The chorioallantoic placenta is richly vascularized with thin, squamous epithelial cells separating the two vascular systems. This morphology differs from the elaborate epithelial cell specializations as occur in some skink species, but is similar to many species. Epithelial cells of the omphaloplacenta are enlarged, as they are in scincids, yet development of the omphaloplacenta includes a vascular pattern known to occur only in gerrhonotine lizards. Histochemical staining properties of the epithelium of the omphalopleure of the omphaloplacenta indicate the potential for protein transport, a function not previously reported for lizards.

Exercise FITT-V during pregnancy: Association with birth outcomes.

BACKGROUND: Prenatal exercise improves birth outcomes, but research into exercise dose-response effects is limited. METHODS: This study is a retrospective, secondary analysis of pooled data from three blinded, prospective, randomized controlled trials. Prenatal exercise frequency, intensity, type, time, and volume (FITT-V) were assessed in supervised sessions throughout pregnancy. Gestational age (GA), neonatal resting heart rate (rHR), morphometrics (body circumferences, weight-to-length and ponderal index) Apgar and reflex scores, and placental measures were obtained at birth. Stepwise regressions and Pearson correlations determined associations between FITT-V and birth outcomes. RESULTS: Prenatal exercise frequency reduces ponderal index (R2 = 0.15, F = 2.76, p = .05) and increased total number of reflexes present at birth (R2 = 0.24, F = 7.89, p < .001), while exercise intensity was related to greater gestational age and birth length (R2 = 0.08, F = 3.14; R2 = 0.12, F = 3.86, respectively; both p = .04); exercise weekly volume was associated with shorter hospital stay (R2 = 0.24, F = 4.73, p = .01). Furthermore, exercise type was associated with placenta size (R2 = 0.47, F = 3.51, p = .01). CONCLUSIONS: Prenatal exercise is positively related to birth and placental outcomes in a dose-dependent manner.

Methylation profiles at birth linked to early childhood obesity.

Childhood obesity represents a significant global health concern and identifying its risk factors is crucial for developing intervention programs. Many "omics" factors associated with the risk of developing obesity have been identified, including genomic, microbiomic, and epigenomic factors. Here, using a sample of 48 infants, we investigated how the methylation profiles in cord blood and placenta at birth were associated with weight outcomes (specifically, conditional weight gain, body mass index, and weight-for-length ratio) at age six months. We characterized genome-wide DNA methylation profiles using the Illumina Infinium MethylationEpic chip, and incorporated information on child and maternal health, and various environmental factors into the analysis. We used regression analysis to identify genes with methylation profiles most predictive of infant weight outcomes, finding a total of 23 relevant genes in cord blood and 10 in placenta. Notably, in cord blood, the methylation profiles of three genes (PLIN4, UBE2F, and PPP1R16B) were associated with all three weight outcomes, which are also associated with weight outcomes in an independent cohort suggesting a strong relationship with weight trajectories in the first six months after birth. Additionally, we developed a Methylation Risk Score (MRS) that could be used to identify children most at risk for developing childhood obesity. While many of the genes identified by our analysis have been associated with weight-related traits (e.g., glucose metabolism, BMI, or hip-to-waist ratio) in previous genome-wide association and variant studies, our analysis implicated several others, whose involvement in the obesity phenotype should be evaluated in future functional investigations.

Implication of viruses in the etiology of preeclampsia.

Preeclampsia is one of the most common disorders that poses threat to both mothers and neonates and a major contributor to perinatal morbidity and mortality worldwide. Viral infection during pregnancy is not typically considered to cause preeclampsia; however, syndromic nature of preeclampsia etiology and the immunomodulatory effects of viral infections suggest that microbes could trigger a subset of preeclampsia. Notably, SARS-CoV-2 infection is associated with an increased risk of preeclampsia. Herein, we review the potential role of viral infections in this great obstetrical syndrome. According to in vitro and in vivo experimental studies, viral infections can cause preeclampsia by introducing poor placentation, syncytiotrophoblast stress, and/or maternal systemic inflammation, which are all known to play a critical role in the development of preeclampsia. Moreover, clinical and experimental investigations have suggested a link between several viruses and the onset of preeclampsia via multiple pathways. However, the results of experimental and clinical research are not always consistent. Therefore, future studies should investigate the causal link between viral infections and preeclampsia to elucidate the mechanism behind this relationship and the etiology of preeclampsia itself.

Special Issue "Physiology and Pathophysiology of the Placenta".

The placenta is a transient but essential organ for normal in utero development, playing several essential functions in normal pregnancy [...].