Placental Research Articles

Placental microphysiological systems: new advances on promising platforms that mimic the microenvironment of the human placenta.

One of the most complex human physiological processes to study is pregnancy. Standard animal models, as well as two-dimensional models, lack the complexity and biological relevance required to accurately study such a physiological process. Recent studies have focused on the development of three-dimensional models based on microfluidic systems, designated as placental microphysiological systems (PMPSs). PMPS devices provide a model of the placental barrier through culturing relevant cell types in specific arrangements and media to mimic the in vivo environment of the maternal-fetal circulation. Here, recent developments of PMPS models for embryo uterine implantation, preeclampsia evaluation, and toxicological screening are presented. Studies that use bioprinting techniques are also discussed. Lastly, recent developments in endometrium microphysiological systems are reviewed. All these presented models showed their superiority compared to standard models in recapitulating the biological environment seen in vivo. However, several limitations regarding the types of cells and materials used for these systems were also widely reported. Despite the need for further improvements, PMPS models contribute to a better understanding of the biological mechanisms surrounding pregnancy and the respective pathologies.

Immunoregulation role of the erythroid cells.

Erythroid cells are the most abundant cells in the human body. In addition to their established function in gas-transportation, erythroid cells at various stages of differentiation have recently been shown to have immunomodulatory roles. Red blood cells may serve as modulators of innate and adaptive immunity, while their immature counterparts, CD71+ erythroid cells (CECs) have important immunomodulatory functions in various contexts. CECs are abundant in human cord blood and placenta, where they contribute to fetomaternal tolerance. CECs also accumulate in patients with infections, tumors, and anemia, and effectively suppress T cells by producing high levels of arginase, reactive oxygen species, programmed death-ligand 1, transforming growth factor β, and/or interleukin-10. Here, we systematically summarize the immunomodulatory functions of erythroid cells and propose some potential therapeutic applications based on their characteristics.

Targeted lipid nanoparticles to prevent trans-placental passage in the ex vivo human placental cotyledon perfusion model.

Medication use during pregnancy poses risks to both the mother and the fetus. These risks include an elevated potential for fetotoxicity due to placental drug transport. Nanomedicines offer a promising solution by potentially preventing trans-placental passage. Targeted nanomedicines could enhance safety and efficacy in treating maternal or placental pathophysiology. Our study investigates placental transfer kinetics of targeted lipid nanoparticles (LNPs) in an ex vivo human placenta cotyledon perfusion model. We collected human placentas for dual-side ex vivo placental perfusions. Targeted LNPs with a fluorescence tag were introduced into the maternal circuit of each placenta. To establish if there was trans-placental passage of LNPs to the fetal circuit, we collected samples from maternal and fetal circuits throughout the six hours of the perfusion. We determined the fluorescence signal using a multi-mode microplate reader and Multiphoton microscopy to localize the LNPs in the placenta tissue. Data from perfused placenta tissue showed no significant transfer of the fluorescently labeled LNPs across the placental barrier to the fetal circuit. Localization of targeted LNPs in tissue samples is mainly observed in the maternal blood space of the placenta. Our results suggest that targeted LNPs present a promising strategic approach to prevent trans-placental passage to the fetus. Our future perspectives involve investigating the efficacy of targeted LNPs as well as loading targeted LNPs with nucleic acid-based therapeutics to investigate their therapeutic potential.

Trypanosoma cruzi-derived exovesicles contribute to parasite infection, tissue damage, and apoptotic cell death during ex vivo infection of human placental explants.

Trypanosoma cruzi, the causative agent of Chagas disease, can be congenitally transmitted by crossing the placental barrier. This study investigates the role of T. cruzi-derived exovesicles (TcEVs) in facilitating parasite infection and the consequent tissue damage and apoptotic cell death in human placental explants (HPEs). Our findings demonstrate that TcEVs significantly enhance the parasite load and induce tissue damage in HPEs, both in the presence and absence of the parasite. Through histopathological and immunohistochemical analyses, we show that TcEVs alone can disrupt the placental barrier, affecting the basal membrane and villous stroma. The induction of apoptotic cell death is evidenced by DNA fragmentation, caspase 8 and 3, and p18 fragment immunodetection. This damage is exacerbated when TcEVs are combined with T. cruzi infection. These findings suggest that TcEVs play a critical role in the pathogenesis of congenital Chagas disease by disrupting the placental barrier and facilitating parasite transmission to the fetus. This study provides new insights into the mechanisms of transplacental transmission of T. cruzi and highlights the potential of targeting TcEVs as a therapeutic strategy against congenital Chagas disease.

Efficacy of Clindamycin in Preventing Abortion and Vertical Transmission of Toxoplasma gondii (PRU Strain) Infection in Pregnant BALB/c Mice

Background: Toxoplasma gondii transmission can occur during pregnancy if the mother contracts the infection for the first time. Treatment strategies include the use of antimicrobial medications and providing supportive care. Spiramycin is commonly used to treat toxoplasmosis in pregnant women and to hinder the disease's transmission. However, its ability to treat the fetus is questionable due to its limited capacity to cross the placental barrier. Additionally, economic constraints and sanctions may impede access to this medication. Objectives: Consequently, in search of an effective treatment, for the first time in Iran, the effectiveness of clindamycin in preventing abortion and vertical transmission of the PRU strain of T. gondii infection in pregnant mice was evaluated. Methods: On the twelfth day of gestation, pregnant mice were exposed to T. gondii and subsequently received treatment with either clindamycin or spiramycin. This resulted in the establishment of four distinct groups: A normal control group, an infected group without treatment, an infected group treated with clindamycin, and another infected group treated with spiramycin. Following these interventions, a series of parasitological evaluations (including microscopic examination and real-time PCR), histopathological evaluations, and immunological assessments were conducted. Results: The findings showed a significant reduction in the number of cysts in the eye and brain (ranging from 77.32% to 90.72%) among the groups treated with clindamycin and spiramycin compared to the control group. Furthermore, treatment with clindamycin, like treatment with spiramycin, was able to suppress inflammatory changes, prevent cell death, and reduce vascular cuffs in the brain, as well as decrease bleeding, placental thrombosis, and the accumulation of inflammatory cells in the placenta. Clindamycin was also effective in diminishing retinal folds, tiny retinal bleeds, and cell vacuolation in eye tissues. Immunologically, treatment in both the spiramycin and clindamycin groups resulted in a decrease in the level of the cytokine TNF-α, indicating an increase in the cellular immune response. In addition, increased levels of IL-10 in the treated infected groups could contribute to the reduction of TNF-α production. Conclusions: Typically, spiramycin is the first choice for treating congenital toxoplasmosis, but clindamycin can be a useful substitute or additional treatment when resistance to primary medications occurs, when there is intolerance, or when access to the main drugs is restricted.

Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation.

Throughout evolution, the placenta has diversified in both structure and cellular composition while maintaining its fundamental function. Trophoblasts are fetal-derived cells responsible for nourishing and protecting the developing fetus and are a universal component of all placentas. While primate placentas exhibit many shared morphological features, species-specific differences in gene expression remain largely unexplored, primarily due to the lack of suitable in vitro models. To address this gap, we developed organoids from rhesus macaque placentas, including trophoblast and maternal-derived decidua types, and compared them with organoids derived from human placentas. We performed comparative single-cell RNA sequencing to delineate shared and distinct transcriptional signatures between rhesus macaque and human trophoblasts. We further defined the differentiation trajectories leading to the multinucleated syncytiotrophoblast, highlighting both shared and unique transcriptional signatures between rhesus macaque and human placentas. This work establishes novel in vitro models of the non-human primate placenta and characterizes distinct trophoblast gene profiles in rhesus macaques and humans, providing insights into interspecies variations in placental biology.

Early-life exposure to polystyrene micro- and nanoplastics disrupts metabolic homeostasis and gut microbiota in juvenile mice with a size-dependent manner

Early-life exposure to different sizes of micro- and nanoplastics (MNPs) affects biotoxicity, which is related not only to the dose but also directly to particle size. In this study, pregnant ICR mice received drinking water containing 5 μm polystyrene microplastics (5 μm PS-MPs) or 0.05 μm polystyrene nanoplastics (0.05 μm PS-NPs) from pregnancy to the end of lactation. Histopathological and molecular biological detection, 16s rRNA sequencing for intestinal flora analysis, and targeted metabolomics analysis were used to look into how early-life exposure to MNPs of various sizes affects young mice's growth and development, gut flora, and metabolism. The outcomes showed that 0.05 μm and 5 μm PS-MNPs can pass through the placental and mammary barriers, and MNPs accumulating in various organs were size-dependent: the greater the accumulation in organs, the smaller the particle size. Further studies found that the larger 5 μm PS-MPs caused only small accumulation in organs, with the main health hazard being the disruption of intestinal barrier and liver function, indirectly causing gut dysbiosis and metabolic disorders. In contrast, the smaller 0.05 μm PS-NPs caused excessive accumulation in organs, not only impaired the function of the intestine and liver, but also caused direct mechanical damage to physical tissues, and ultimately resulted in more severe intestinal and metabolic disorders. Our findings underline the size-dependent risks associated with micro- and nanoplastics exposure early in life and highlight the necessity for tailored approaches to address health damages from early MNPs exposure.

Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring.

Prenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17A's action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated a transfer of transgenic IL-17A across the placental barrier, which triggered the development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.

KLF4 regulates trophoblast function and associates with unexplained recurrent spontaneous abortion

BackgroundRecurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions before 20 weeks with the same spouse [1]. However, approximately 50% of RSA cases of unknown cause are classified as unexplained recurrent spontaneous abortion (URSA). Potential factors include decreased trophoblast cell migration and invasion, leading to impaired placental implantation and maintenance of the normal maternal-fetal interface. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the potential role and mechanism of KLF4 in regulating URSA by influencing the invasion and migration ability of trophoblast cells.MethodsWe firstly identified 817 differentially expressed genes by performing a difference analysis of the dataset GSE121950 [2] related to recurrent abortion, and intersected the top 10 genes obtained respectively by the three algorithms: DMNC, MNC, and EPC using Venn Diagram.To detect the expression levels of core genes, villi samples were obtained from normal pregnant women and patients with URSA. RT-qPCR analysis revealed a significant difference in KLF4 mRNA expression and KLF4 was then analyzed. Trophoblast cell lines HTR8 and JEG3 were used to investigate the effect of KLF4 on trophoblastic function. Wound healing and transwell assays was performed to detect the invasion and migration of trophoblast cells. The expression of epithelial-mesenchymal transition(EMT) molecules were detected by RT-qPCR and western blot. Promoter detection and epigenetic modification were detected by chromatin immunoprecipitation (ChIP) assay. Molecular nuclear localization was detected by immunofluorescence and subcellular fractionation. Miscarried mice model was used to study the effects of KLF4 on URSA induced by reduced trophoblast invasion and migration.ResultsKLF4 is highly expressed in the villi of patients with URSA. KLF4 inhibits the expression level of H3R2ME2a in trophoblast cells by regulating the transcriptional level and nuclear translocation of PRMT6, thereby inhibiting the possible regulatory mechanism of trophoblastic invasion and providing a potential treatment strategy for URSA in vivo.ConclusionsThe KLF4/PRMT6/H3R2ME2a axis regulates mechanisms associated with unexplained recurrent spontaneous abortion by regulating trophoblast function.

Parallel Spectral Tuning of a Cone Visual Pigment Provides Evidence for Ancient Deep-Sea Adaptations in Cetaceans.

Dichromatic color vision is mediated by two cone visual pigments in many eutherian mammals. After reentry into the sea, early cetaceans lost their violet-sensitive visual pigment (short wavelength-sensitive 1) independently in the baleen and toothed whale ancestors and thus obtained only monochromatic cone vision. Subsequently, losses of the middle/long wavelength-sensitive (M/LWS) pigment have also been reported in multiple whale lineages, leading to rhodopsin (RH1)-mediated rod monochromatic vision. To further elucidate the phenotypic evolution of whale visual pigments, we assessed the spectral tuning of both M/LWS and RH1 from representative cetacean taxa. Interestingly, although the coding sequences for M/LWS are intact in both the pygmy right whale and the Baird's beaked whale, no spectral sensitivity was detected in vitro. Pseudogenization of other cone vision-related genes is observed in the pygmy right whale, suggesting a loss of cone-mediated vision. After ancestral sequence reconstructions, ancient M/LWS pigments from cetacean ancestors were resurrected and functionally measured. Spectral tuning of M/LWS from the baleen whale ancestor shows that it is green sensitive, with a 40-nm shift in sensitivity to a shorter wavelength. For the ancestor of sperm whales, although no spectral sensitivity could be recorded for its M/LWS pigment, a substantial sensitivity shift (20 to 30 nm) to a shorter wavelength may have also occurred before its functional inactivation. The parallel phenotypic evolution of M/LWS to shorter wavelength sensitivity might be visual adaptations in whales allowing more frequent deep-sea activities, although additional ecological differentiations may have led to their subsequent losses.

PUS6 in pseudorabies virus participates in the process of inhibiting antigen presentation by inhibiting the assembly of peptide loading complex.

Pseudorabies virus (PRV) can establish lifelong latent infection in peripheral nervous ganglion, and persistent infections in peripheral blood lymphocytes. Establishing an infection in the lymphocytes does not only enable the PRV to escape host immune surveillance but pass through the placental barrier, leading to fetal death and abortion. Due to the pathogenicity of the PRV, it poses a huge challenge in its prevention and control. The PRV escapes host immunity through downregulation of swine leukocyte antigen class I (SLA I) molecules on infected cells. However, data on the molecular mechanisms of the SLA I suppression remains scant. Here, in order to verify the effect of candidate proteins PRV pUL44 and pUS6 on PRV immune escape related molecules SLA I and peptide loading complex (PLC), we detected the expression of SLA I and PLC components after expressing PRV pUL44 and pUS6. The effects of pUS6 and pUL44 on SLA I and PLC were analyzed by qRT-PCR and Western blot at mRNA and protein level, respectively. Cells expressing pUS6 or pUL44 genes showed a significantly suppressed expression of surface and total SLA I molecules. In addition, unlike UL44, the US6 gene was shown to downregulate the transporter associated with antigen processing 1 (TAP1), TAP2 and Tapasin molecules. The results show that PRV pUS6 may participate in virus immune escape by directly regulating the SLA I, TAP dimer and Tapasin molecules, thus blocking the transportation of TAP-bound peptides to the ER to bind SLA I molecules. We provide a theoretical basis on the mechanism of TAP mediated immune escape by the PRV.

Genetic characteristics and pathogenicity of variant porcine parvovirus 1 in northern China

Porcine parvovirus type 1 (PPV1) can lead to reproductive disorders in pregnant sows, including stillbirth, mummification, embryonic death, and infertility (SMEDI syndrome). In this study, we isolated and identified 10 PPV1 strains in northern China, with genomes around 5 kb long and minor deletions in the 127-nt repeat region. The sequence analysis results showed that compared with strain NADL-2 (Reference strain), eight amino acid substitutions on the NS1 protein and fourteen amino acid substitutions on the VP2 protein were found in the ten isolates. Because the JX strain exhibited reduced neutralizing activity induced by commercially available vaccines in vitro, it was selected for challenge experiments in sows at 35 days of gestation. Mutant strain JX not only caused viremia, but also mild edema and mild inflammation in the trachea, lungs, lymph nodes, reproductive organs, and some intestines of the pregnant sows. Strain JX also caused fetal congestion and organ infection after penetrating the placental barrier. In conclusion, this study focused on the variation and evolution of PPV1 in northern China, screened a strain with reduced neutralizing activity, and determined that it has a certain degree of pathogenicity.

The extension of mammalian pregnancy required taming inflammation: Independent evolution of extended placentation in the tammar wallaby.

In the first live-bearing mammals, pregnancy was likely short and ended with a brief period of inflammatory maternal-fetal interaction. This mode of reproduction has been retained in many marsupials. While inflammation is key to successful implantation in eutherians, a key innovation in eutherians is the ability to switch off this inflammation after it has been initiated. This extended period, in which inflammation is suppressed, likely allowed for an extended period of placentation. Extended placentation has evolved independently in one lineage of marsupials, the macropodids (wallabies and kangaroos), with placentation lasting beyond the 2 to 4 d seen in other marsupial taxa, which allows us to investigate the role of inflammation response after attachment in the extension of placentation in mammals. By comparing gene expression changes at attachment in three marsupial species, the tammar wallaby, opossum, and fat-tailed dunnart, we show that inflammatory attachment is an ancestral feature of marsupial implantation. In contrast to eutherians, where attachment-related (quasi-) inflammatory reaction is even involved in epitheliochorial placentation (e.g., pig), this study found no evidence of a distinct attachment-related reaction in wallabies. Instead, only a small number of inflammatory genes are expressed at distinct points of gestation, including IL6 before attachment, LIF throughout placentation, and prostaglandins before birth. During parturition, a more distinct inflammatory reaction is detectable, likely involved in precipitating the parturition cascade similar to eutherians. We suggest that in wallaby, extended gestation became possible by avoiding an inflammatory attachment reaction, which is a different strategy than seen in eutherians.

MCM proteins are up-regulated in placentas of women with reduced insulin sensitivity.

In the first trimester of pregnancy the human placenta grows rapidly, making it sensitive to changes in the intrauterine environment. To test whether exposure to an environment in utero often associated with obesity modifies placental proteome and function, we performed untargeted proteomics (LC-MS/MS) in placentas from 19 women (gestational age 35-48 days, i.e. 5+0-6+6 weeks). Maternal clinical traits (body mass index, leptin, glucose, C-peptide and insulin sensitivity) and gestational age were recorded. DNA replication and cell cycle pathways were enriched in the proteome of placentas of women with low maternal insulin sensitivity. Driving these pathways were the minichromosome maintenance (MCM) proteins MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7 (MCM-complex). These proteins are part of the pre-replicative complex and participate in DNA damage repair. Indeed, MCM6 and γH2AX (DNA-damage marker) protein levels correlated in first trimester placental tissue (r = 0.514, P<0.01). MCM6 and γH2AX co-localized to nuclei of villous cytotrophoblast cells, the proliferative cell type of the placenta, suggesting increased DNA damage in this cell type. To mimic key features of the intrauterine obesogenic environment, a first trimester trophoblast cell line, i.e., ACH-3P, was exposed to high insulin (10 nM) or low oxygen tension (2.5% O2). There was a significant correlation between MCM6 and γH2AX protein levels, but these were independent of insulin or oxygen exposure. These findings show that chronic exposure in utero to reduced maternal insulin sensitivity during early pregnancy induces changes in the early first trimester placental proteome. Pathways related to DNA replication, cell cycle and DNA damage repair appear especially sensitive to such an in utero environment.

Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study.

Micro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. The Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. In this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. In the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. As plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. DERR1-10.2196/63176.

Maternal infection with SARS-CoV-2 during early pregnancy induces hypoxia at the maternal-fetal interface.

The coronavirus disease 2019 (COVID-19) pandemic increases the risk of adverse fetal outcomes during pregnancy. Maternal infection during pregnancy, particularly with cytomegalovirus (CMV), hepatitis B and C virus, and human immunodeficiency virus can have detrimental effects on both mother and fetus, potentially leading to adverse outcomes such as spontaneous abortion or neonatal infection. However, the impact of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection on the maternal-fetal interface remains poorly understood. In this study, we initially utilised immunofluorescence and immunohistochemical to investigate placental samples from pregnant women who were infected with SARS-CoV-2 during the first trimester. Our data indicate that infection in the first trimester induces an upregulation of hypoxia inducible factor (HIF) levels at the maternal-fetal interface. Subsequently, single-cell RNA sequencing and metabolomics sequencing analyses reveal alterations in maternal-fetal interface. Remarkably, immune cells exhibited low expression levels of HIF possibly associated with immune activation. Furthermore, our findings demonstrate a gradual reduction in transcriptome and metabolic changes as gestation progressed beyond 12-16 weeks compared to samples obtained at 6-8 weeks gestation. Overall, our study suggests that early-stage SARS-CoV-2 infection during the first trimester leads to severe hypoxia and aberrant cell metabolism at the maternal-fetal interface which gradually resolves as pregnancy progresses. Nevertheless, these abnormal changes may have long-term implications for maternal-fetal interface development.

Common tenrecs (Tenrec ecaudatus) reduce oxygen consumption in hypoxia and in hypercapnia without concordant changes to body temperature or heart rate.

Common tenrecs (Tenrec ecaudatus) are fossorial mammals that use burrows during both active and hibernating seasons in Madagascar and its neighboring islands. Prevailing thought was that tenrecs hibernate for 8-9months individually, but 13 tenrecs were removed from the same sealed burrow 1m deep from the surface. Such group hibernation in sealed burrows presumably creates a hypoxic and/or hypercapnic environment and suggests that this placental mammal may have an increased tolerance to hypoxia and hypercapnia. Higher tolerances to hypoxia and hypercapnia have been documented for other mammals capable of hibernation and to determine if this is the case for tenrecs, we exposed them to acute hypoxia (4h of 16 or 7% O2), progressive hypoxia (2h of 16, 10 and 4% O2), or progressive hypercapnia (2h of 2, 5 and 10% CO2) at cold (16°C) or warm (28°C) ambient temperatures (Ta). Oxygen equilibrium curves were also constructed on the whole blood of tenrecs at 10, 25, and 37°C to determine if hemoglobin (Hb)-O2 affinity contributes to hypoxia tolerance. In animals held at 16°C, normoxic and normocapnic levels of oxygen consumption rate ( ), body temperature (Tb), and heart rate (HR) were highly variable between individuals. This inter-individual variation was greatly reduced in animals held at 28°C for oxygen consumption rate and body temperature. Both hypoxia (acute and progressive) and progressive hypercapnia led to decreases in as well as the variation in between animals held at 16°C. The fall in oxygen consumption rate in 7% O2 independent of changes in body temperature in tenrecs held at 16°C is unique and not consistent with the typical hypoxic metabolic response seen in other hibernating species that depends on concomitant falls in Tb. In animals held at 28°C, exposure to O2 levels as low as 4% and CO2 levels as high as 10% had no significant effect on , HR, or Tb, indicative of high tolerance to both hypoxia and hypercapnia. High variation in heart rate remained between individuals in all gas compositions and at all temperatures. Tenrec Hb-O2 affinity was similar to other homeothermic placental mammals and likely does not contribute to the increased hypoxia tolerance. Ultimately, our results suggest changes in Ta dictate physiological responses to hypoxia or hypercapnia in tenrecs, responses more characteristic of reptiles than of most placental mammals. Given that numerous anatomical and physiological characteristics of tenrecs suggest that they may be representative of an ancestral placental mammal, our findings suggest the typical hypoxic metabolic response evolved later in mammalian evolution.

DRUG PRESCRIPTION FOR PREGNANT WOMEN IN DENTISTRY: Literature review

The development of medications was a great achievement for humanity, however, it is necessary to prescribe and use them with caution, especially in certain patients who require special attention, such as pregnant women, for whom medication is generally not recommended. prescription of medications due to the numerous adverse effects that exist and the possibility of these crossing the placental barrier, however, in certain situations it is necessary to prescribe medications even if the patient is pregnant. This work aims to create an information cluster about the prescription of medications for pregnant women by dental surgeons, which can serve as an information source for both dentistry students and professionals who have already graduated. A review of the narrative literature was carried out regarding the prescription of medications for pregnant patients by dental surgeons with the general objective of presenting how the dental therapeutic methods are for pregnant women, taking into account the dangers and advantages of the use of medications during pregnancy and breastfeeding. Specifically: to analyze the prevalence of oral diseases in pregnant women and the relationship with dental treatments during pregnancy; to investigate the main recipes and difficulties of dental professionals and students. Scientific articles related to the proposed topic were used to compose the bibliographic base of this work, available in the online databases BVSalud, PUBMed, Lilacs, Scielo and Google Scholar, presented in Portuguese and published between the years 2020 and 2024. At the end of this work, it is concluded that drug therapy in pregnant and breastfeeding women requires a meticulous assessment of the risks involved. Therefore, it is essential that dentists write prescriptions carefully and responsibly, with the aim of preventing unwanted effects related to the use of medications, ensuring that the treatment is safe and effective for patients. A careful approach contributes to oral health and general well-being.

Fabrication and characterization of nanohydroxyapatite/chitosan/decellularized placenta scaffold for bone tissue engineering applications

Novel biomaterials are necessary to fabricate biomimetic scaffolds for bone tissue engineering. In the present experiment, we aimed to fabricate and evaluate the osteogenic properties of nanohydroxyapatite/chitosan/decellularized placenta (nHA.Cs.dPL) composite scaffolds. The human placenta was decellularized (dPL), characterized, and digested in pepsin to form the hydrogel. nHA.Cs.dPL scaffolds were fabricated using salt leaching/freeze drying and evaluated for their morphology, chemical composition, swelling, porosity, degradation, mechanical strength, and biocompatibility. Saos-2 cells were seeded on scaffolds, and their osteogenic properties were investigated by evaluating alkaline phosphatase (ALP), osteocalcin (OCN), collagen type 1 (COL I) expression, and calcium deposition under osteogenic differentiation. The dPL was prepared with minimized DNA content and a well-preserved porous structure. Scaffolds were highly porous with interconnected pores and exhibited appropriate swelling and degradation rates supporting saos-2 cell attachment and proliferation. dPL improved scaffold physicochemical features and increased cell proliferation, ALP, OCN, COL I expression, and calcium deposition under osteogenic differentiation induction. nHA.Cs.dPL composite scaffolds provide a 3D microenvironment with superior physicochemical features that support saos-2 cell adhesion, proliferation, and osteogenic differentiation.

Comparative Analyses Reveal Conserved and Modified Steps in the Testis Descent and Scrotum Development in Mouse and Opossum.

In many mammals, the testes descend from its abdominal position on the mesonephric kidney and are housed in the scrotum. It has been speculated that metatherians and eutherians might have acquired the scrotal testis independently because metatherians have the scrotum cranially to the phallus, while eutherians, such as humans and mice, possess it caudally. Rather, recent studies based on sequence comparisons of testis-descent-related genes indicate that the metatherian-eutherian common ancestor might already possess the descent mechanisms. To further elucidate the path of scrotal testis evolution, it is informative to compare the processes of the descent and scrotum development between metatherian and eutherian model animals. In this study, we histologically and molecularly compare these processes in gray short-tailed opossum (Monodelphis domestica), the most commonly used metatherian experimental model, and compare them with those in mouse. Our observations indicate that, while transabdominal phase of the descent appears to be largely similar, scrotal phase differs due to their distinct scrotum positions. Our cell-labeling analyses and dynamic expression of Gsc1 reveal extensive cell/tissue rearrangements in murine scrotal development. In contrast, Gsc1 is not expressed in the developing genitalia and scrotal primordium of the opossum. Our results suggest recruitment of new regulatory pathways for the scrotum development and the scrotal phase of the testis descent during the evolution of eutherian mammals.