Project description:Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 104 (0.66 × 104) and 2.09 × 104 (0.9 × 104) particles per mm3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers' residential BC exposure during pregnancy (0.63-2.42 µg per m3). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards.

| S-EPMC6748955 | biostudies-literature

Small non-coding RNAs transfer through mammalian placenta and directly regulate fetal gene expression.

Project description: Not available

| S-EPMC4444809 | biostudies-literature

Placental transfer of tofacitinib in the <i>ex vivo</i> dual-side human placenta perfusion model.

Project description:Tofacitinib is a small molecule Janus kinase (JAK) inhibitor, introduced to the European market in 2017, for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. In the treatment of women with autoimmune diseases, pregnancy is a relevant issue, as such diseases typically affect women in their reproductive years. Currently, there is limited data on the use of tofacitinib during pregnancy. To estimate the extent of placental transfer in the absence of clinical data, we conducted ex vivo dual-side perfused human placental cotyledon perfusions. Term placentas were perfused for 180 min with tofacitinib (100 nM, added to the maternal circuit) in a closed-closed configuration. At the end of the perfusions, drug concentrations in the maternal and fetal reservoirs were near equilibrium, at 35.6 ± 5.5 and 24.8 ± 4.7 nM, respectively. Transfer of tofacitinib was similar to that observed for the passive diffusion marker antipyrine (100 µg/mL, added to the maternal reservoir). Final antipyrine maternal and fetal concentrations amounted to 36.9 ± 3.0 and 36.7 ± 1.3 µg/mL, respectively. In conclusion, in the ex vivo perfused placenta tofacitinib traverses the placental barrier rapidly and extensively. This suggests that substantial fetal tofacitinib exposure will take place after maternal drug dosing.

| S-EPMC10825226 | biostudies-literature

Novel Insights into Concepts and Directionality of Maternal⁻Fetal Cholesterol Transfer across the Human Placenta.

Project description:Cholesterol is indispensable for cellular membrane composition and function. It is also a precursor for the synthesis of steroid hormones, which promote, among others, the maturation of fetal organs. A role of the ATP-binding-cassette-transporter-A1 (ABCA1) in the transport of maternal cholesterol to the fetus was suggested by transferring cholesterol to apolipoprotein-A-1 (apo-A1), but the directionality of the apoA-1/ABCA1-dependent cholesterol transport remains unclear. We isolated primary trophoblasts from term placentae to test the hypotheses that (1) apoA-1/ABCA1 dispatches cholesterol mainly towards the fetus to support fetal developmental maturation at term, and (2) differentiated syncytiotrophoblasts (STB) exert higher cholesterol transport activity than undifferentiated cytotrophoblasts (CTB). As experimental models, we used (1) trophoblast monolayers grown on Transwell® system consisting of apical (maternal-like) and basal (fetal-like) compartments, and (2) trophoblasts grown on conventional culture plates at CTB and STB stages. Surprisingly, apoA-1-mediated cholesterol efflux operated almost exclusively at the apical-maternal side, where ABCA1 was also localized by immunofluorescence. We found greater cholesterol efflux capacity in STB, which was increased by liver-X-receptor agonist treatment and decreased by ABCA1 inhibition. We conclude that at term the apoA-1/ABCA1 pathway is rather involved in cholesterol transport to the mother than in transfer to the fully developed fetus.

| S-EPMC6121295 | biostudies-literature

Argonaute immunoprecipitation reveals mis-annotation of human microRNAs

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-04-23 | GSE184535 | GEO

Cell fractionation reveals mis-annotation of human microRNAs

Project description:MicroRNAs (miRNAs) form the sequence recognition component of the RNA-induced silencing complex (RISC), bringing Argonaute (AGO) and other RISC-associated proteins to target transcripts where they mediate post-transcriptional gene silencing. High-throughput sequencing has helped to catalogue several thousand human miRNAs, as well as a plethora of other small RNAs derived from larger transcripts. Here, we take a closer inspection of sequencing data derived from cellular fractionation and AGO-RNA immunoprecipitation and find that a subset of small RNAs, despite being denoted as miRNAs, are in fact almost exclusively nuclear and do not associate with AGO. Experimental validation of a select number of these small RNAs also fails to show endogenous miRNA-like activity, suggesting they are degradation products from larger transcripts that have been mis-annotated. Despite this, the presumed miRNA functions of almost 20 of these have collectively been the subject of several hundred publications, emphasising the need to filter unlikely miRNA candidates from sequencing data and large miRNA-sequence repositories.

2025-04-23 | GSE183863 | GEO

Identification of maternally regulated fetal gene networks in the placenta with a novel embryo transfer system in mice.

Project description:The mechanisms for provisioning maternal resources to offspring in placental mammals involve complex interactions between maternally regulated and fetally regulated gene networks in the placenta, a tissue that is derived from the zygote and therefore of fetal origin. Here we describe a novel use of an embryo transfer system in mice to identify gene networks in the placenta that are regulated by the mother. Mouse embryos from the same strain of inbred mice were transferred into a surrogate mother either of the same strain or from a different strain, allowing maternal and fetal effects on the placenta to be separated. After correction for sex and litter size, maternal strain overrode fetal strain as the key determinant of fetal weight (P < 0.0001). Computational filtering of the placental transcriptome revealed a group of 81 genes whose expression was solely dependent on the maternal strain [P < 0.05, false discovery rate (FDR) < 0.10]. Network analysis of this group of genes yielded highest statistical significance for pathways involved in the regulation of cell growth (such as insulin-like growth factors) as well as those involved in regulating lipid metabolism [such as the low-density lipoprotein receptor-related protein 1 (LRP1), LDL, and HDL], both of which are known to play a role in fetal development. This novel technique may be generally applied to identify regulatory networks involved in maternal-fetal interaction and eventually help identify molecular targets in disorders of fetal growth.

| S-EPMC3092334 | biostudies-literature

Reply: Carbon Dioxide Narcosis or Sleep Deprivation?

Project description: Not available

| S-EPMC6543469 | biostudies-literature

Argonaute immunoprecipitation reveals mis-annotation of human microRNAs [miRNA-seq]

2025-04-23 | GSE184534 | GEO