Search Results (40)

Microplastics constitute an emerging contaminant of major concern in Latin America, where human exposure predominantly occurs through ingestion of drinking water and marine/estuarine food chains. This review synthesises available evidence on occurrence, exposure pathways, toxicological mechanisms, and regional public health risks, while examining regulatory and monitoring limitations that constrain effective risk management. Reported concentrations in drinking water show a wide range (1–1194 particles/L), dominated by PET, PP, and PS, with fibres and fragments as the main morphotypes. In commercial marine species, prevalence reaches 70–100%, with burdens up to 44 particles/g in oysters and ~90 particles/250 g in mussels. Estimated Daily Intake is 2–5 times higher in children (e.g., Chile: 13.03 vs. 5.59 particles/day in adults). Toxicological mechanisms include oxidative stress, chronic inflammation (NF-κB pathway), endocrine disruption, intestinal dysbiosis, systemic translocation, and placental transfer, exacerbated by vectorization of local co-contaminants (Hg from mining, Cd/Pb from agriculture). Risk indices indicate extreme danger in Brazil, Chile, and Ecuador, where data are available. Significant geographic and methodological gaps persist, with Brazil dominating research (~50–60%). Multicenter biomonitoring, harmonised surveillance networks, and SDG-aligned policies are urgently needed to reduce exposure burdens, protect vulnerable populations, and advance toward comprehensive regional risk assessment. Full article

Background: Microplastics (MPs) have rapidly emerged as pervasive environmental contaminants with growing implications for human health. Evidence now shows that MP exposure may begin during pregnancy and extend into infancy. Foetal exposure to MP raises questions about MP presence within reproductive organs, maternal–foetal MP transfer and the potential impact of MP on women’s reproductive health. Objectives: To synthesise current evidence on the presence and distribution of microplastics in the female reproductive system and pregnancy-related organs. Methods: A systematic review of literature was conducted using Embase and Medline databases, supplemented by reference screening and manual searches. Studies were eligible if they examined MP in human female reproductive organs or pregnancy-related tissues and were published in English. Results: Eleven studies met the inclusion criteria. Across studies, MP detection varied substantially due to differences in sampling protocols, analytical techniques, and particle size detection thresholds. Cross-contamination and analytical method variability remained major methodological concerns. MP were consistently identified in follicular fluid, placental tissue, amniotic fluid, cord blood, and meconium. Conclusions: The presence of MP in both maternal and foetal compartments supports the possibility of in utero maternal-foetal MP transfer. A standardised protocol should be used to assess MP presence and MP’s impact on organs and tissues. The current variability of diagnostic tests, the lack of cofounding variables control and the reduced sample sizes limit the ability to determine how clinically relevant MP exposure is during pregnancy and to women’s reproductive health. Full article

The medical condition of pregnancy-associated breast cancer (PABC) requires oncologists to determine the best way to protect both the mother and the fetus during cancer treatment. The safety profile of taxanes, including paclitaxel and docetaxel, in the second and third trimesters of pregnancy remains unclear despite well-established anthracycline-based regimens (e.g., doxorubicin). High-risk breast cancer subtypes such as triple negative breast cancer (TNBC) and human epidermal growth factor receptor (HER2)-positive disease require taxane chemotherapy as standard treatment in nonpregnant patients. Objective: This paper aims to gather available data about the safety, timing and fetal outcomes related to taxane chemotherapy during PABC, focusing on pharmacological and clinical guidance. Methods: A targeted literature review of PubMed and Scopus databases was performed to identify case series, cohort studies, and clinical guidelines addressing taxane use during pregnancy. This was not conducted as a formal systematic review or meta-analysis, but as a comprehensive narrative synthesis of available data. Results: The pharmacological properties of paclitaxel and docetaxel limit their placental transfer. Paclitaxel has not been associated with increased congenital anomalies; however, the long-term developmental data remain limited. Similarly, docetaxel administration shows no increase in major malformations. The most common approach used in PABC is to administer anthracyclines first and taxanes after 16–18 weeks’ gestation. The adverse effects experienced by pregnant patients match those experienced by nonpregnant patients. Conclusions: Taxanes can be used with caution after the first trimester in patients with PABC, especially in high-risk cases following anthracycline treatment. The absence of randomized trials combined with limited developmental data highlight the need for more standardized treatment approaches, aligning with current guideline recommendations. Full article

Human chorionic gonadotropin (hCG) is a pregnancy biomarker, and five forms of this hormone are involved in female physiological regulation. β-core fragment hCG (bcf-hCG) is a fragment of hCG whose biological role in female reproduction has not been completely elucidated. This study aimed to investigate its role in embryo implantation and maintenance of a pregnancy-supportive environment. We analyzed the protein expression pattern of bcf-hCG in the intrauterine environment during early pregnancy by performing western blotting and immunohistochemistry with a monoclonal anti-bcf-hCG antibody. We performed a cell proliferation assay in the presence of bcf-hCG compared with intact hCG. We conducted an ex vivo study by performing intrauterine injection of bcf-hCG or intact hCG in mice. Endometrial thickness was measured using histological methods, and uterine gene and protein expression were analyzed following intrauterine injection of bcf-hCG. We evaluated the effect of bcf-hCG on embryo implantation in the uterus. bcf-hCG was highly abundant in the placenta and epithelial stromal glands of the uterine endometrium during early pregnancy and significantly induced proliferation of a stromal epithelial cell line. Intrauterine injection of bcf-hCG induced expression of specific genes and proteins, including homeobox A10, for embryo implantation and placental development. Upon embryo transfer, the implantation rate of bcf-hCG-treated embryos was higher than that of control embryos. In conclusion, bcf-hCG plays a role in the proliferation of glandular epithelial cells in the endometrium and placenta during early pregnancy. Therefore, bcf-hCG is an early-phase pregnancy biomarker that maintains the initial phase of pregnancy. Full article

From fertilisation to delivery, calcium must be transported into and within the foetoplacental unit for intracellular signalling. This requires very rapid, precisely located Ca²⁺ transfers. In addition, from around the eighth week of gestation, increasing amounts of calcium must be routed directly from maternal blood to the foetus for bone mineralisation through a flow-through system, which does not impact the intracellular Ca²⁺ concentration. These different processes are mediated by numerous membrane-sited Ca²⁺ channels, transporters, and exchangers. Understanding the mechanisms is essential to direct interventions to optimise foetal development and postnatal bone health and to protect the mother and foetus from pre-eclampsia. Ethical issues limit the availability of human foetal tissue for study. Our insight into the processes of placental Ca²⁺ handling is advancing rapidly, enabled by developing genetic, analytical, and computer technology. Because of their diverse sources, the reports of new findings are scattered. This review aims to pull the data together and to highlight areas of uncertainty. Areas needing clarification include trafficking, membrane expression, and recycling of channels and transporters in the placental microvilli; placental metabolism of vitamin D in gestational diabetes and pre-eclampsia; and the vascular effects of increased endothelial Orai expression by pregnancy-specific beta-1-glycoproteins PSG1 and PSG9. Full article

Vaccination in pregnancy is important to protect the mother and fetus from infectious diseases. The transfer of maternal antibodies across the placenta during pregnancy can continue to protect the neonate for several months after birth while the neonatal adaptive immune system develops. Several pathogens have been shown to impair the transplacental transfer of maternal antibodies, including human immunodeficiency virus, malaria, the severe acute respiratory syndrome coronavirus 2, and cytomegalovirus. This review discusses the mechanisms contributing to decreased transplacental antibody transfer in the setting of maternal infections, such as changes in antibody glycosylation profile, maternal hypergammaglobulinemia, and placental injury. The frequency of epidemics is increasing, and pregnant people are more likely to become exposed to novel pathogens now than they were in the past. Understanding the mechanisms by which infectious diseases impair maternal–fetal antibody transfer is important for pandemic preparedness to maximize the impact of maternal vaccination for child health. Full article

Phenols, parabens, and phthalates (PPPs) are suspected or known endocrine disruptors. They are used in consumer products that pregnant women and their progeny are exposed to daily through the placenta, which could affect offspring health. This review aims to compile data from cohort studies and in vitro and in vivo models to provide a summary regarding placental transfer, fetoplacental development, and the predisposition to adult diseases resulting from maternal exposure to PPPs during the gestational period. In humans, using the concentration of pollutants in maternal urine, and taking the offspring sex into account, positive or negative associations have been observed concerning placental or newborn weight, children’s BMI, blood pressure, gonadal function, or age at puberty. In animal models, without taking sex into account, alterations of placental structure and gene expression linked to hormones or DNA methylation were related to phenol exposure. At the postnatal stage, pollutants affect the bodyweight, the carbohydrate metabolism, the cardiovascular system, gonadal development, the age of puberty, sex/thyroid hormones, and gamete quality, but these effects depend on the age and sex. Future challenges will be to explore the effects of pollutants in mixtures using models and to identify the early signatures of in utero exposure capable of predicting the health trajectory of the offspring. Full article

Maternal vaccinations administered prior to conception or during pregnancy enhance the immune protection of newborn infants against many pathogens. A feasibility experiment was conducted to determine if monkeys can be used to model the placental transfer of maternal antibody against SARS-CoV-2. Six adult rhesus monkeys were immunized with adjuvanted recombinant-protein antigens comprised of receptor-binding domain human IgG1-Fc fusion proteins (RBD-Fc) containing protein sequences from the ancestral-Wuhan or Gamma variants. The female monkeys mounted robust and sustained anti-SARS-CoV-2 antibody responses. Blood samples collected from their infants after delivery verified prenatal transfer of high levels of spike-specific IgG, which were positively correlated with maternal IgG titers at term. In addition, an in vitro test of ACE2 neutralization indicated that the infants’ IgG demonstrated antigen specificity, reflecting prior maternal immunization with either Wuhan or Gamma-variant antigens. All sera showed stronger ACE2-RBD binding inhibition when variants in the assay more closely resembled the vaccine RBD sequence than with more distantly related variants (i.e., Delta and Omicron). Monkeys are a valuable animal model for evaluating new vaccines that can promote maternal and infant health. Further, the findings highlight the enduring nature and safety of the immune protection elicited by an adjuvanted recombinant RBD-Fc vaccine. Full article

Background: The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism. Methods: A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included. Results: During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects. Conclusions: Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects. Full article

The trophoblast cells are responsible for the transfer of nutrients between the mother and the foetus and play a major role in placental endocrine function by producing and releasing large amounts of hormones and growth factors. Syncytiotrophoblast cells (STB), formed by the fusion of mononuclear cytotrophoblasts (CTB), constitute the interface between the foetus and the mother and are essential for all of these functions. We performed transcriptome analysis of human placental samples from two control groups—live births (LB), and stillbirths (SB) with a clinically recognised cause—and from our study group, idiopathic stillbirths (iSB). We identified 1172 DEGs in iSB, when comparing with the LB group; however, when we compared iSB with the SB group, only 15 and 12 genes were down- and upregulated in iSB, respectively. An assessment of these DEGs identified 15 commonly downregulated genes in iSB. Among these, several syncytiotrophoblast markers, like genes from the PSG and CSH families, as well as ALPP, KISS1, and CRH, were significantly downregulated in placental samples from iSB. The transcriptome analysis revealed underlying differences at a molecular level involving the syncytiotrophoblast. This suggests that defects in the syncytial layer may underlie unexplained stillbirths, therefore offering insights to improve clinical obstetrics practice. Full article

Given the broad and intense use of plastic, society is being increasingly affected by its degradation and by-products, particularly by microplastics (MPs), fragments smaller than 5 mm in size, and nanoplastics (NPs), with sizes less than 1 µm. MPs and NPs may enter the body primarily through inhalation, consumption, and skin contact. Once ingested, MPs can penetrate tissues, deviating to other parts of the body and potentially affecting important cellular pathways such as nonconforming chemokine receptors that control the communication between the fetus and the mother. Consequently, the potential health harm induced via MP internalization is a major issue, evidenced by multiple studies demonstrating harmful consequences in diverse animal models and human cells. Here, an overview of the various modes of exposure to MPs and NPs is presented, including inhalation, placental transfer, ingestion, breastmilk consumption, and skin absorption, as well as placental and fetal toxicity due to plastic particles based on animal and in vitro studies. Though MPs in our environment are becoming more recognized, their developmental toxicity is still scarcely known. Besides negatively affecting pregnancy, MPs and NPs have been shown to potentially harm the developing fetus, given their ability to cross the placental barrier. Still, considerable gaps remain in our understanding of the dispersion and toxicity of these particles in the environment and the precise types of NPs and MPs bearing the greatest dangers. As a result, we advocate for larger-scale epidemiological investigations, the development of novel approaches for measuring NP and MP exposures, and the necessity of understanding the toxicity of various kinds of NPs to guide future research efforts. Full article

Introduction: Docosahexaenoic acid (DHA) is an n-3 long chain polyunsaturated fatty acid critical for fetal brain development that is transported to the fetus from the mother by the placenta. The lysophosphatidylcholine (LPC) transporter, Major Facilitator Superfamily Domain Containing 2a (MFSD2a), is localized in the basal plasma membrane of the syncytiotrophoblast of the human placenta, and MFSD2a expression correlates with umbilical cord blood LPC-DHA levels in human pregnancy. We hypothesized that placenta-specific knockdown of MFSD2a in pregnant mice reduces phospholipid DHA accumulation in the fetal brain. Methods: Mouse blastocysts (E3.5) were transduced with an EGFP-expressing lentivirus containing either an shRNA targeting MFSD2a or a non-coding sequence (SCR), then transferred to pseudopregnant females. At E18.5, fetuses were weighed and their placenta, brain, liver and plasma were collected. MFSD2a mRNA expression was determined by qPCR in the brain, liver and placenta and phospholipid DHA was quantified by LC-MS/MS. Results: MFSD2a-targeting shRNA reduced placental mRNA MFSD2a expression by 38% at E18.5 (n = 45, p < 0.008) compared with SCR controls. MFSD2a expression in the fetal brain and liver were unchanged. Fetal brain weight was reduced by 13% (p = 0.006). Body weight, placenta and liver weights were unaffected. Fetal brain phosphatidyl choline and phosphatidyl ethanolamine DHA content was lower in fetuses with placenta-specific MFSD2a knockdown. Conclusions: Placenta-specific reduction in expression of the LPC-DHA transporter MFSD2a resulted in reduced fetal brain weight and lower phospholipid DHA content in the fetal brain. These data provide mechanistic evidence that placental MFSD2a mediates maternal–fetal transfer of LPC-DHA, which is critical for brain growth. Full article

Twin pregnancy with a complete hydatidiform mole and coexisting fetus (CHMCF) is an exceedingly rare condition with an incidence of about 1 in 20,000–100,000 pregnancies. It can be detected by prenatal ultrasonography and an elevated maternal serum beta-human chorionic gonadotropin (BhCG) level. Herein, the author reports a case of CHMCF which was incidentally diagnosed through pathologic examination without preoperative knowledge. The 41-year-old woman, transferred due to preterm labor, delivered a female baby by cesarean section at 28 + 5 weeks of gestation. Clinically, the surgeon suspected placenta accreta on the surgical field, and the placental specimen was sent to the pathology department. On gross examination, focal vesicular and cystic lesions were identified separately from the normal-looking placental tissue. The pathologic diagnosis was CHMCF and considering the fact that placenta accreta was originally suspected, invasive hydatidiform mole was not ruled out. After radiologic work-up, metastatic lung lesions were detected, and methotrexate was administered in six cycles at intervals of every two weeks. The author presents the clinicopathological features of this unexpected CHMCF case accompanied by pulmonary metastasis, compares to literature review findings, and emphasizes the meticulous pathologic examination. Full article

Quantification of fetal drug exposure remains challenging since sampling from the placenta or fetus during pregnancy is too invasive. Currently existing in vivo (e.g., cord blood sampling) and ex vivo (e.g., placenta perfusion) models have inherent limitations. A placenta-on-a-chip model is a promising alternative. A systematic search was performed in PubMed on 2 February 2023, and Embase on 14 March 2023. Studies were included where placenta-on-a-chip was used to investigate placental physiology, placenta in different obstetric conditions, and/or fetal exposure to maternally administered drugs. Seventeen articles were included that used comparable approaches but different microfluidic devices and/or different cultured maternal and fetal cell lines. Of these studies, four quantified glucose transfer, four studies evaluated drug transport, three studies investigated nanoparticles, one study analyzed bacterial infection and five studies investigated preeclampsia. It was demonstrated that placenta-on-a-chip has the capacity to recapitulate the key characteristics of the human placental barrier. We aimed to identify knowledge gaps and provide the first steps towards an overview of current protocols for developing a placenta-on-a-chip, that facilitates comparison of results from different studies. Although models differ, they offer a promising approach for in vitro human placental and fetal drug studies under healthy and pathological conditions. Full article

Per- and polyfluoroalkyl substances (PFASs) are important and ubiquitous environmental contaminants worldwide. These novel contaminants can enter human bodies via various pathways, subsequently posing risks to the ecosystem and human health. The exposure of pregnant women to PFASs might pose risks to the health of mothers and the growth and development of fetuses. However, little information is available about the placental transfer of PFASs from mothers to fetuses and the related mechanisms through model simulation. In the present study, based upon a review of previously published literature, we initially summarized the exposure pathways of PFASs in pregnant women, factors affecting the efficiency of placental transfer, and mechanisms associated with placental transfer; outlined simulation analysis approaches using molecular docking and machine learning to reveal the mechanisms of placental transfer; and finally highlighted future research emphases that need to be focused on. Consequently, it was notable that the binding of PFASs to proteins during placental transfer could be simulated by molecular docking and that the placental transfer efficiency of PFASs could also be predicted by machine learning. Therefore, future research on the maternal–fetal transfer mechanisms of PFASs with the benefit of simulation analysis approaches is warranted to provide a scientific basis for the health effects of PFASs on newborns. Full article