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Antibody-like biopharmaceuticals cross the placenta by utilizing existing transport pathways (e.g., FcRn receptor). There are limited data evaluating this transfer during organogenesis in any species. Understanding placental transfer of antibody-like biopharmaceuticals can help to predict risk of developmental toxicity across species, including humans. To complement previously published placental transfer data in the rat with humanized IgGΔ2 (hIgG2), the timing and magnitude of transfer in the cynomolgus monkey and embryo/fetal biodistribution of maternally administered I-radiolabeled hIgG2 was quantified on gestation days (GD) 35, 40, 50, 70, and 140 using gamma counting and whole body autoradiography 24 hr following intravenous injection. Chorioallantoic placental tissues were collected at all time points for Western Blot analysis with anti-FcRn antibody. Maternally administered I-hIgG2 was found in embryo/fetal tissues at all time points, including organogenesis. Embryo/fetal plasma I-hIgG2 concentration increased during gestation, but only slightly up to GD 70 in embryo/fetal tissues, with hIgG2 tissue concentrations generally similar between GD70 and 140. The embryo/fetal:maternal I-hIgG2 plasma concentration ratio was approximately 2.3 fold higher on GD 140, in comparison to ratios on GD 40. Importantly, placental FcRn protein expression was confirmed at all timepoints. These data demonstrate placental transfer of hIgG2 in a nonhuman primate model, and at levels comparable to the rat model, raising the potential for adverse developmental outcomes by direct antibody binding to biological targets.
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http://dx.doi.org/10.1002/bdr2.1615 | DOI Listing |
Commun Med (Lond)
December 2024
Environmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
Background: Assisted reproductive technology (ART) has been associated with increased risks for growth disturbance, disrupted imprinting as well as cardiovascular and metabolic disorders. However, the molecular mechanisms and whether they are a result of the ART procedures or the underlying subfertility are unknown.
Methods: We performed genome-wide DNA methylation (EPIC Illumina microarrays) and gene expression (mRNA sequencing) analyses for a total of 80 ART and 77 control placentas.
Extracell Vesicles Circ Nucl Acids
June 2024
Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Host-bacteria and bacteria-bacteria interactions can be facilitated by extracellular vesicles (EVs) secreted by both human and bacterial cells. Human and bacterial EVs (BEVs) propagate and transfer immunogenic cargos that may elicit immune responses in nearby or distant recipient cells/tissues. Hence, direct colonization of tissues by bacterial cells is not required for immunogenic stimulation.
View Article and Find Full Text PDFJ Dairy Sci
December 2024
Department of Animal Sciences, University of Florida, Gainesville, 31608, USA. Electronic address:
The placenta plays a pivotal role in fetal development and the dam's subsequent lactation performance, as it facilitates nutrient transfer, heat dissipation, gas exchange with the growing fetus, and regulates key hormones essential for mammary gland development. Heat stress experienced during gestation and lactation can significantly reduce the placenta's capacity to perform these critical functions. To investigate the impact of heat stress, trials were conducted over the summer months of 2020, 2022, and 2023 in Florida.
View Article and Find Full Text PDFToxicol Res (Camb)
December 2024
National Institutes for Food and Drug Control, No. 31 of Huatuo road, Daxing district, Beijing 100260, PR China.
Plastics are the most frequently used materials in people's daily life, and the primary and secondary microplastics generated from them may harm the health of adults. This paper focuses on the summary of the existence of microplastics in many objects most closely related to people in daily life, the toxicological influences it causes in cultured human normal cells and organoids, and the prospects for future research directions. Micro- and nano-plastics (MNPs) are found in almost all of our everyday products, such as food, drink, and daily necessities, etc.
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