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STUDY QUESTION Is exposure to environmental chemicals associated with modifications of placental morphology and function? SUMMARY ANSWER Phthalates, a class of ubiquitous chemicals, showed an association with altered placental weight, placental vascular resistance (PVR), and placental efficiency. WHAT IS KNOWN ALREADY Only a few epidemiological studies have assessed the effects of phenols and phthalates on placental health. Their results were affected by exposure measurement errors linked to the rapid excretion of these compounds and the reliance on a limited number of spot urine samples to assess exposure. STUDY DESIGN, SIZE, DURATION A prospective mother–child cohort, with improved exposure assessment for non-persistent chemicals, recruited participants between 2014 and 2017. Sample size ranged between 355 (placental parameters measured at birth: placental weight and placental-to-fetal weight ratio (PFR): a proxy for placental efficiency) and 426 (placental parameters measured during pregnancy: placental thickness and vascular resistance). PARTICIPANTS/MATERIALS, SETTING, METHODS Phenols (four parabens, two bisphenols, triclosan, and benzophenone-3), 13 phthalate metabolites, and two non-phthalate plasticizer metabolites were measured in within-subject pools of repeated urine samples collected during the second and third trimesters of pregnancy (median = 21 samples/trimester/woman). Placental thickness and PVR were measured during pregnancy. The placenta was weighed at birth and the PFR was computed. Both adjusted linear regression and Bayesian Kernel Machine Regression were used to evaluate associations between phenols and phthalates (alone or as a mixture) and placental parameters. Effect modification by child sex was also investigated. MAIN RESULTS AND THE ROLE OF CHANCE Several phthalate metabolites were negatively associated with placental outcomes. Monobenzyl phthalate (MBzP) concentrations, during the second and third trimesters of pregnancy, were associated with a decrease in both placental weight at birth (β = −20.1 g [95% CI: −37.8; −2.5] and β = −17.4 g [95% CI: −33.2; −1.6], for second and third trimester, respectively) and PFR (β = −0.5 [95% CI: −1, −0.1] and β = −0.5 [95% CI: −0.9, −0.1], for the second and third trimester, respectively). Additionally, MBzP was negatively associated with PVR during the third trimester (β = −0.9 [95% CI: −1.8; 0.1]). Mono-n-butyl phthalate (MnBP), was negatively associated with PVR in both trimesters (β = −1.3, 95% CI: [−2.3, −0.2], and β = −1.2, 95% CI: [−2.4, −0.03], for the second and third trimester, respectively). After stratification for child sex, Σ diisononyl phthalate (DiNP) (either second or third-trimester exposures, depending on the outcomes considered) was associated with decreased PVR in the third trimester, as well as decreased placental weight and PFR in males. No associations were observed for phenol biomarkers. LIMITATIONS, REASONS FOR CAUTION False positives cannot be ruled out. Therefore, chemicals that were associated with multiple outcomes (MnBP and DiNP) or reported in existing literature as associated with placental outcomes (MBzP) should be considered as the main results. WIDER IMPLICATIONS OF THE FINDINGS Our results are consistent with in vitro studies showing that phthalates target peroxisome proliferator-activated receptor γ, in the family of nuclear receptors involved in key placental development processes such as trophoblast proliferation, migration, and invasion. In addition to placental weight at birth, we studied placental parameters during pregnancy, which could provide a broader view of how environmental chemicals affect maternal–fetal exchanges over the course of pregnancy. Our findings contribute to the increasing evidence indicating adverse impacts of phthalate exposure on placental health. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the French Research Agency—ANR (MEMORI project ANR-21-CE34-0022). The SEPAGES cohort was supported by the European Research Council (N°311765-E-DOHaD), the European Community's Seventh Framework Programme (FP7/2007-206—N°308333-892 HELIX), the European Union's Horizon 2020 research and innovation programme (N° 874583 ATHLETE Project, N°825712 OBERON Project), the French Research Agency—ANR (PAPER project ANR-12-PDOC-0029-01, SHALCOH project ANR-14-CE21-0007, ANR-15-IDEX-02 and ANR-15-IDEX5, GUMME project ANR-18-CE36-005, ETAPE project ANR-18-CE36-0005—EDeN project ANR-19-CE36-0003-01), the French Agency for Food, Environmental and Occupational Health & Safety—ANSES (CNAP project EST-2016-121, PENDORE project EST-2016-121, HyPAxE project EST-2019/1/039, PENDALIRE project EST-2022-169), the Plan Cancer (Canc'Air project), the French Cancer Research Foundation Association de Recherche sur le Cancer—ARC, the French Endowment Fund AGIR for chronic diseases—APMC (projects PRENAPAR, LCI-FOT, DysCard), the French Endowment Fund for Respiratory Health, the French Fund—Fondation de France (CLIMATHES—00081169, SEPAGES 5–00099903, ELEMENTUM—00124527). N.J. was supported by a doctoral fellowship from the University Grenoble Alpes. V.M. was supported by a Sara Borrell postdoctoral research contract (CD22/00176), granted by Instituto de Salud Carlos III (Spain) and NextGenerationEU funds. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT02852499. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite its involvement in several human pathophysiological processes, the cellular prion protein (PrPC) remains enigmatic. During the last ten years, PrPC has also been reported to be implicated in several human cancers, the molecular mechanisms of which are under investigation. In some tumors, elevated expression of PrPC protein is associated with poor patient prognosis. At the cellular level, high PrPC expression in tumor cells is associated with the acquisition of stemness1-like characteristics, metastatic and invasive process, and resistance to chemotherapy. This review explores PrPC's expression in different types of cancer and addresses its potential as a target for their treatment. The cellular prion protein (PrPC) is a glycoprotein anchored to the cell surface by glycosylphosphatidylinositol (GPI). PrPC is expressed both in the brain and in peripheral tissues. Investigations on PrPC's functions revealed its direct involvement in neurodegenerative and prion diseases, as well as in various physiological processes such as anti-oxidative functions, copper homeostasis, trans-membrane signaling, and cell adhesion. Recent findings have revealed the ectopic expression of PrPC in various cancers including gastric, melanoma, breast, colorectal, pancreatic, as well as rare cancers, where PrPC promotes cellular migration and invasion, tumor growth, and metastasis. Through its downstream signaling, PrPC has also been reported to be involved in resistance to chemotherapy and tumor cell apoptosis. This review summarizes the variance of expression of PrPC in different types of cancers and discusses its roles in their development and progression, as well as its use as a potential target to treat such cancers. [ABSTRACT FROM AUTHOR]

Background: The placenta performs crucial physiological functions to ensure normal fetal development. Few epidemiological studies investigated placental weight sensitivity to phthalates and phenols. Objective: Our goal was to explore whether maternal exposure to select phthalates and phenols is associated with changes in placental weight at birth and in placental-to-birth weight ratio (PFR). Methods: Placental weight and birth weight were available for 473 mother-son pairs in the EDEN (Etude des Determinants pre et postnatals du developpement et de la sante de l'Enfant) cohort for whom 9 phenols (4 parabens, 2 dichlorophenols, triclosan, benzophenone-3, bisphenol A) and 11 phthalate metabolites were measured in spot urine samples collected between weeks 23 and 29 of gestation. We used adjusted Elastic Net penalized regression models (ENET) to select biomarkers associated with placental weight, birth weight and PFR. Unpenalized effect estimates were then obtained by fitting linear regression models simultaneously adjusted for the ENET-selected biomarkers and a priori chosen confounders. Results: The multipollutant ENET model for placental weight retained four biomarkers: triclosan and monocarboxy-isononyl phthalate (MCNP), which were negatively associated with placental weight, and benzophenone-3 and the sum of parabens, which were positively associated with this outcome. The ENET model for PFR retained two phthalate metabolites [MCNP and monocarboxy-isooctyl phthalate (MCOP)], which were negatively associated with this outcome. Discussion: The positive association between the sum of parabens and placental weight was consistent with results of a previous study among 49 male births. Our results provide preliminary evidence of possible associations between other compounds such as triclosan, benzophenone-3, MCNP, and MCOP and both placental weight and PFR. These associations were not reported in previous studies and should be seen as hypothesis generating. Studies relying on repeated assessments of exposure in prospective mother-child cohorts are needed to substantiate the plausibility of the hypotheses generated by our results. https://doi.org/10.1289/EHP3523, Introduction Placental Weight and Placental Efficiency The placenta is the main interface between the mother and the fetus. This organ performs crucial physiological functions such as nutrient, oxygen, and waste [...]