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Psychedelic and psychedelic-adjacent substances, including 3,4-methylenedioxymethamphetamine (MDMA) and classic serotonergic hallucinogens, are undergoing renewed therapeutic investigation and remain in non-medical use. Inadvertent exposure during early, unrecognized pregnancy is clinically plausible, yet pregnancy-specific safety evidence is limited. To map and synthesize the extent, characteristics, and limitations of primary human evidence on prenatal exposure to MDMA, psilocybin, and classic hallucinogens (lysergic acid diethylamide (LSD), mescaline/peyote, and N,N-dimethyltryptamine (DMT)/ayahuasca), and to identify clinically relevant evidence gaps for perinatal counseling and pharmacovigilance. Peer-reviewed primary human studies (cohort, case-control, cross-sectional, case series, case reports, and brief reports) describing prenatal exposure with reported maternal, obstetric, neonatal, congenital anomaly, or child neurodevelopmental outcomes were included. Animal and preconception-only studies were excluded. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library were searched from inception to March 2025. Supplementary methods included Google Scholar screening and citation tracking. Data were charted in duplicate using a standardized form and synthesized descriptively by substance and outcome domain. Consistent with scoping methodology, no formal risk-of-bias assessment or meta-analysis was undertaken. Twenty-three primary human sources (1968-2020) met inclusion criteria: MDMA (n = 11), LSD (n = 11), and mescaline/peyote (n = 1). No eligible primary human pregnancy outcome studies were identified for psilocybin or DMT/ayahuasca. The evidence base was heterogeneous and predominantly comprised small cohorts, teratology service follow-up reports, and case-based publications, frequently limited by self-reported exposure, polysubstance confounding, and inconsistent outcome definitions. Human evidence on prenatal psychedelic exposure remains sparse and methodologically constrained. Absence of data for several substances should not be interpreted as evidence of safety. Clinicians should counsel with explicit acknowledgment of uncertainty while supporting harm reduction and appropriate follow-up. Structured perinatal pharmacovigilance and ethically designed evidence-generation strategies are needed as therapeutic psychedelic research expands. What we know about psychedelic drug exposure during pregnancy Some people may be exposed to psychedelic drugs such as MDMA (“ecstasy”), LSD, or psilocybin during pregnancy, often before they realize they are pregnant. As interest in psychedelic therapies grows, clinicians are increasingly asked about possible risks to pregnancy and child development. In this review, we examined all available human studies that reported pregnancy or child outcomes following exposure to psychedelic or psychedelic-related substances. We found that the human evidence base is very limited and mostly consists of small observational studies, case reports, and follow-up data from teratology information services. Most available studies focus on MDMA or LSD, while there is little to no direct human pregnancy outcome data for substances such as psilocybin or ayahuasca. Because the available evidence is sparse and highly variable, it is not possible to reliably estimate the risks of miscarriage, birth defects, or long-term child development following psychedelic exposure during pregnancy. This review highlights important gaps in current knowledge and explains why careful, individualized clinical counselling is needed when such exposures occur. The findings are relevant for clinicians, patients, and researchers involved in drug safety and pregnancy care.

Since 2008, the open-access internet portal "Embryotox" has provided evidence-based information on drug safety during pregnancy and breastfeeding. The German website, designed for health care professionals, comprises fact sheets about 400 drugs and is maintained by the Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy at the Charité - Universitätsmedizin Berlin. In 2024, it was accessed more than 5 million times. This study aimed to evaluate who is using the website, how it is being used, and to what extent it meets users' needs. Data were collected between 2022 and 2023 through a sequential mixed methods design incorporating explanatory and exploratory elements. Online questionnaire 1 contained questions on user characteristics, clinical specifics of use, comprehensibility, and changes in risk assessment or drug therapy following fact sheet use. Qualitative data were generated through semistructured phone interviews, with interviewees sampled from the main user groups identified in questionnaire 1 (patients, physicians, pharmacists, and midwives). Kuckartz's content analysis was used to analyze data on users' trust and the functions of website use for different stakeholder groups. Online questionnaire 2 collected data from the main user groups on their decision-making based on Embryotox fact sheets. This questionnaire was developed based on the findings from semistructured interviews on the functions of website use. Answers in both questionnaires included multiple-choice options or ratings on a Likert scale from 0 (not at all) to 10 (fully); data were analyzed using descriptive statistics. Questionnaire 1 was completed by 14,562 users, including 10,860 patients, 1676 physicians, 550 pharmacists, and 364 midwives. Of the physicians, 27.2% (456/1676) were obstetricians and gynecologists, and 22.7% (381/1676) were general practitioners. For physicians, the mean of comprehensibility ratings was 9.39 (pharmacists 9.25; midwives 9.14), and for patients 8.80. Following fact sheet use, 66.6% (9694/14,562) of all users changed their risk perception, and 22.3% (2252/10,083) of users in a specific treatment setting considered changing drug treatment. Qualitative content analysis revealed that users highly trusted the information in the fact sheets for a number of reasons, including recommendations from other users, the scientific basis of the website, and the authority of the Embryotox Center as a university-based specialist department for drug safety in pregnancy and lactation. Functions of fact sheet use differed depending on the stakeholder group. A total of 793 users, mostly physicians and patients, fully completed questionnaire 2, specifying typical clinical situations and benefits of fact sheet use for shared decision-making. Benefits included facilitating the decision-making process and increasing confidence in it. The information provided in the Embryotox fact sheets was generally perceived as both comprehensible and trustworthy, supporting and facilitating the decision-making process. Embryotox is used successfully by health care providers and patients in routine health care settings, helping to improve drug safety for pregnant and breastfeeding women.

The evidence gap relating to the risk of congenital anomalies (CA) associated with first trimester medication exposure in pregnancy is well recognized. We describe the EUROmediCAT network and databases, and the methodological approach to pregnancy pharmacovigilance. Multidisciplinary expertise includes CA diagnosis and epidemiology, pharmacoepidemiology, pharmacology and teratology. The EUROmediCAT central database comprises standardized data from 19 EUROCAT CA registries in 14 countries, including more than 40 000 CA cases 1995-2021 with first trimester medication exposure data recorded, and a population coverage of 14.6 million births, growing by more than 650 000 births per year. The distributed database enables federated data analysis across eight countries which can link data from CA registries to electronic healthcare data, with population coverage of up to 900 000 births per year for linkage to maternal prescriptions, of which 300 000 births per year for linkage also to data on all births. The databases have enabled a variety of study designs: case-malformed control studies, cohort studies, disease cohort studies, signal detection studies, prevalence and ecological studies, and medication utilization studies. A key strength is that studies of CA risk can address accurately the specificity of risk by type of CA. EUROmediCAT presents a unique data and expert resource for tackling the enormous evidence gap regarding the safety of medication during pregnancy. There is a well‐recognized need for more evidence about the safety of medication use in early pregnancy to guide optimal medication choice. This paper describes the EUROmediCAT network and its databases, and how these databases can be used to generate evidence about medication safety in pregnancy. A single central database includes data from congenital anomaly registries in 14 countries of Europe, with information on medication exposure of each case. This covers a population of 14.6 million births 1995–2021, and is growing by more than 650 000 births per year. Databases accessible in eight countries link congenital anomaly registries to prescription data (covering over 900 000 births per year), and to all births (covering over 300 000 births per year). These data can also be shared for large scale research. A key strength of the EUROmediCAT network and databases is that particular attention is paid to accurate information on the risk of specific types of congenital anomaly. EUROmediCAT presents a unique data and expert resource for tackling the enormous evidence gap regarding the safety of medication during pregnancy.

Etanercept is a tumor necrosis factor inhibitor frequently used to control ankylosing spondylitis (AS) in women of reproductive age, yet data on its safety during breastfeeding are limited. We report a case of an infant who developed somnolence, hypotonia, feeding difficulties, and a concomitant infection temporally associated with maternal etanercept therapy during lactation and discuss implications for breastfeeding. A 33-year-old woman with AS delivered a healthy female infant by cesarean section at 36 + 5 weeks' gestation and began exclusive breastfeeding. At 11 weeks postpartum, she initiated etanercept 25 mg subcutaneously once weekly for her active disease. During treatment, the infant developed prolonged sleep, somnolence, feeding difficulty, and hypotonia, followed within a week by low-grade fever, cough, and nasal congestion. After three doses, etanercept was discontinued, and she was referred to our teratology information service. Approximately 2 weeks after the last dose, the infant's respiratory symptoms worsened, and diarrhea developed, prompting emergency admission. Laboratory evaluation showed leukocytosis, elevated C-reactive protein, and a nasopharyngeal swab, which was positive for rhinovirus/enterovirus. Symptoms resolved with supportive care and azithromycin by treatment days 4-5. At 9 months of age, the infant has had no other health issues. This case illustrates the difficulty of interpreting adverse events in breastfed infants exposed to maternal biologic medications. Although current evidence suggests no clinically severe adverse effects, minimal infant exposure, and a low risk of clinically relevant immunosuppression with etanercept during breastfeeding, individualized counseling and careful monitoring of exposed infants remain essential.

Urea transporter (UT) inhibitors are a promising class of diuretics, as selective inhibitors targeting UT-A subtypes have demonstrated considerable therapeutic potential. Herein, we employ a two-round progressive hotspot pocket-based virtual screening approach combined with biological validation to identify M353-0039 as a highly potent and selective inhibitor of UT-A2. We conduct cryo-electron microscopy to solve the structures of UT-A2 bound with the two inhibitors, M353-0039 and E822-1968, at the resolution of 2.7 Å and 2.9 Å respectively, and elucidate the structural mechanism underlying the superior efficacy and selectivity of M353-0039. Compared with the inhibitor HQA2 and E822-1968, M353-0039 occupies a deeper binding pocket and forms more interactions with UT-A2, thus leading to greater inhibitory potency. We demonstrate that the selectivity of M353-0039 is driven by the nonconserved residues C285 and G322 within the "T-T" subpocket of UT-A2. Finally, we validate the selective effects of M353-0039 in inhibiting UT-A2 function both in mouse models and hepatic cell. These findings not only identify a selective inhibitor as a tool that can be applied to elucidate the unique physiological roles of UT-A2 but also provide an available method for efficiently developing UT-A-selective inhibitors with potent activity as the next-generation diuretics.

The objective of this systematic review and meta-analysis was to assess the risk of any and major congenital malformations and other adverse pregnancy outcomes following maternal exposure to glucagon-like peptide-1 receptor agonists during the periconceptional period and pregnancy. We conducted a systematic literature search of the PubMed, MEDLINE, Embase, Web of Science, and Reprotox electronic databases from inception through January 2026. Seven cohort studies encompassing over 40,000 exposed pregnancies were included. Maternal exposure to glucagon-like peptide-1 receptor agonists at any time during pregnancy was not associated with a statistically significant increase in any congenital malformations (OR, 1.11; 95% CI 0.82-1.51). First-trimester exposure did not significantly increase the risk of major congenital malformations (OR, 1.39; 95% CI 0.73-2.65). Furthermore, no significant risk increase was observed for stillbirth, spontaneous abortion, small for gestational age, or preterm birth. A significant association for urinary malformations was noted (OR, 1.24; 95% CI 1.05-1.47) based exclusively on unadjusted data. Maternal exposure to glucagon-like peptide-1 receptor agonists does not demonstrate a statistically significant association with major congenital malformations, stillbirth, spontaneous abortion, small for gestational age, or preterm birth. The urinary malformation signal relies on unadjusted estimates, likely reflecting residual confounding. These findings provide cautiously reassuring evidence regarding reproductive safety, though the certainty of evidence remains low.

External injuries and morphological deformities may serve as useful indicators when assessing the welfare of wild animals, as they can be easily observed, be scored in a non-disruptive manner, and likely correlate with reductions in welfare in many contexts. However, the welfare effects of injuries and deformities have so far been mostly examined for animals in captivity. In contrast, the many fish living in the wild have received considerably less attention, especially in relation to naturally occurring causes, such as parasitism, predation attempts, and intra-specific conflict. Here, I attempt to quantify the prevalence of injuries and deformities in wild fish by conducting a targeted review of six relevant journals, and suggest areas where future research would be particularly useful. The results indicate that both anthropogenic and non-anthropogenic factors can cause injuries and deformities in wild fish, and that many of the focal species (i.e. the species studied in the reviewed papers) are closely related. The average prevalence of injuries and/or deformities was 15% across studies. Despite the existence of potential confounding factors (e.g. a selection bias in terms of focal populations and species), these results highlight the potential importance of injuries and deformities as determinants and indicators of fish welfare in the wild.

Ulcerative colitis (UC) remission is marked by gut microbiota restructuring, but how microbial metabolites influence immune-mediated tissue repair is unclear. Here, we demonstrate that oral vancomycin alleviates colitis symptoms in murine models, mirroring its clinical efficacy in inducing remission in patients with UC. Mechanistically, vancomycin's therapeutic effect is achieved by reducing deoxycholic acid (DCA). We reveal that DCA impairs mucosal repair driven by group 2 innate lymphoid cells (ILC2s) by inducing ER stress through direct binding to thioredoxin-related transmembrane protein 2 (TMX2). This interaction disrupts TMX2's role in protein folding, triggering unresolved unfolded protein response via hyperactivation of PERK/eIF2α signaling, which suppresses the production of pro-healing molecules by ILC2s. Pharmacological inhibition of PERK phosphorylation restores ILC2 function and accelerates colitis resolution. Our work uncovers a pathogenic microbiota/DCA/ILC2 axis that obstructs mucosal healing and positions vancomycin as a targeted strategy to eliminate DCA, thereby promoting UC remission.

Abdominal aortic aneurysm (AAA) is a life-threatening degenerative aortic disease that primarily affects older individuals. While macrophages are central to AAA pathogenesis, the regulatory role of the stimulatory G protein α subunit (Gsα) in macrophages remains poorly understood. In this study, using an Angiotensin Ⅱ-induced abdominal aortic aneurysm model on male mice, we demonstrate that macrophage-specific Gnas deficiency significantly attenuates AAA progression. Mechanistically, Gsα directly interacts with NLRP3 to promote inflammasome activation. Further cellular investigations indicate that Gsα maintains NLRP3 stability by sterically hindering its association with the E3 ubiquitin ligase BTRC, thereby preventing NLRP3 ubiquitination and subsequent degradation. Furthermore, lipid nanoparticles (LNPs)-mediated delivery of Gsα siRNA to monocytes/macrophages effectively suppresses NLRP3 expression and markedly reduces AAA progression in vivo. Our findings identify Gsα as a regulator in the activation of the NLRP3 inflammasome and provide a potential therapeutic target for AAA.

Breast cancer (BC) metastasis remains a major cause of mortality, yet the molecular mechanisms driving this process are incompletely understood. This study identifies TMEM216, a transmembrane protein implicated in ciliary homeostasis, as a suppressor of lung metastasis in BC. Using mammary-specific Tmem216 knockout mice, we demonstrate that Tmem216 deficiency promotes lung metastasis without affecting primary tumor proliferation. Clinical analyses reveal reduced TMEM216 expression in metastatic lesions and aggressive cell lines, correlating with poor patient distant metastasis-free survival. Mechanistically, TMEM216 interacts with IGF1R and binds to IRS4 via the conserved K79-D1049 interaction, disrupting the IGF1R-IRS4 complex formation and suppressing IGF pathway activation. Rescue experiments in vitro and in vivo confirm that TMEM216-mediated metastasis inhibition depends on IGF signaling modulation. Tissue microarray analyses further establish an inverse correlation between TMEM216 levels and IGF1R phosphorylation in BC patients, with low TMEM216 expression associated with advanced metastasis. These findings delineate TMEM216 as a critical regulator of the IGF1R-IRS4 axis, offering therapeutic opportunities for targeting metastatic BC.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatocellular carcinoma (HCC) and confers resistance to immunotherapy. However, the underlying mechanisms remain unclear. We aimed to elucidate how the lipid-rich microenvironment of MASLD-HCC drives immune suppression and to identify actionable targets. Dendritic cell (DC)-CD8+ T cell interactions in HCC tissues were analyzed by multiplexed immunofluorescence staining. Mechanistic studies employed high-fat diet (HFD)-induced MASLD-HCC mouse models, genetic or pharmacological inhibition of Tim-3, and DC depletion or adoptive transfer. Lipid peroxidation, ferroptosis, and immune interactions were assessed using flow cytometry, transcriptomics, and functional assays. The therapeutic efficacy of Tim-3 blockade, alone or combined with anti-PD-1 therapy or lenvatinib, was evaluated in preclinical models. HFD reshaped the hepatic tumor immune microenvironment by inducing DC depletion and CD8+ T cell dysfunction, facilitating liver tumor progression. In human steatohepatitis-related HCC, DC infiltration and DC-CD8+ T cell interactions were markedly impaired, and high DC-specific Tim-3 expression correlated with poor prognosis. Mechanistically, the lipid-rich microenvironment induced DC depletion via Tim-3-dependent lipid peroxidation and ferroptosis. Genetic or pharmacological inhibition of Tim-3 in DCs attenuated lipid peroxidation, restored DC survival and CD8+ T cell activation, and suppressed tumor growth. Moreover, Tim-3 blockade synergized effectively with both anti-PD-1 and lenvatinib to achieve sustained tumor control. Our findings establish Tim-3 as a pivotal regulator of DC ferroptosis in metabolic liver cancer. Combining Tim-3 blockade with standard therapies represents a promising strategy to restore immune surveillance in MASLD-HCC. Our findings identify Tim-3 as a crucial metabolic immune checkpoint that governs dendritic cell ferroptosis and dendritic cell-mediated antitumor immunity in metabolic liver cancer. Targeted blockade of Tim-3 in dendritic cells holds great therapeutic potential for the treatment of steatohepatitis-related hepatocellular carcinoma, particularly for patients with metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma who exhibit resistance to anti-PD-1 therapy.

Although regulatory responses to safety signals have been studied, pregnancy-specific data and their dissemination to medical professionals remain unclear. This study examined the characteristics and temporal trends of teratological safety signals prompting the European Medicines Agency to implement risk minimization measures. A secondary aim was to investigate how information on these signals, independent of regulatory communication, was disseminated to medical professionals in the Netherlands. Teratological safety signals from 2002 to 2022 were retrieved from the European Pharmacovigilance Issues Tracking Tool. For each signal, we recorded the dates of market authorization, first spontaneous report, scientific publication, regulatory decision and dissemination through the Teratology Information Service (TIS) and Dutch professional journals. The source of the signal (spontaneous reports, scientific literature or otherwise) was assessed. Time intervals between events were calculated and visualized. Twenty-four safety signals pertaining to fetal teratogenesis were identified. At the time of regulatory action, medicines had been on the market for a median of 23.9 years (range 3.2-59.3). Cases or studies published in the scientific literature were the origin for most (n = 18, 75%) teratological safety signals. Amendments of the product information was a regulatory action for all signals; eight (33%) also triggered Direct Healthcare Professional Communications. Apart from these regulatory communications, information may have reached healthcare professionals through scientific literature or other channels, sometimes before and sometimes alongside regulatory decisions. Teratological safety signals are predominantly scientific literature-driven and often arise decades after marketing. Scientific publications and TIS may provide early guidance, frequently preceding regulatory decisions.

Syndactyly, also known as mulefoot, is one of the most common physical extremity malformations. In pigs, syndactyly has been associated with genetic or environmental factors and occurs as an isolated defect or in association with other congenital anomalies.This case report aimed to describe a radiographically confirmed case of syndactyly in a piglet. A 17-day-old 6.2 kg piglet showed syndactyly in all four limbs. Although this anomaly did not affect the patient's daily activities, it was a congenital malformation of clinical and zootechnical relevance. A complete blood count, morphometric measurements, and limb radiographs were performed. Radiographs revealed a fusion of phalangeal bones in the forelimbs and an accessory phalangeal element located axially between the principal digits in the hindlimbs. The complete blood count revealed mild leukocytosis. Syndactyly occurs during embryonic development when the phalanges do not separate. Its severity can vary from a simple skin union to complete bone fusion. Syndactyly etiology is multifactorial and involves genetic and environmental factors.

Clinical lactation studies are valuable to guide pharmacotherapy during breastfeeding, but are not easy to conduct. This paper reports on challenges and mitigation strategies while conducting the UmbrelLACT study, a prospective observational lactation study. The UmbrelLACT study includes breastfeeding women taking a relevant medicine (eg, absence of safety evidence during lactation) and after feasibility verification (eg, access to bioanalytical assay). Participants collect human milk samples at home over 24 hours. Optionally, maternal and infant blood samples are collected, together with self-reported questionnaires on clinical maternal and child variables. Medicine concentrations and estimated infant exposure (eg, daily and relative infant dose) are determined. Regarding informed consent, study objectives should be carefully phrased to prevent pharmacotherapy avoidance due to a lack of safety information. On sample collection, the study team should provide all necessary materials if not available at home, including an electric breast pump. Due to the milk expressions over 24 hours, the infant might miss soothing moments. This can be mitigated by giving the breast after expressing the milk for study purposes, creating alternative soothing moments. Sample handling might be complicated by additional steps needed for certain compounds. A bioanalysis method should be available or developed for the milk matrix. Finding the assay might be challenging, but it can be facilitated by a network of specialised labs. In the UmbrelLACT study, pharmacokinetic values are collected fragmentarily. This results in the need for data pooling with data from the literature. In contrast, at-home sampling and multidisciplinary collaboration are clear strengths. It is feasible to tailor the approach to each participant and compound, to minimise the burden on the patient and their family. While there are limitations related to the pragmatic design, the opportunities of this lactation study outweigh the challenges to result in clinically significant scientific observations. NCT06042803.

Programmed death-ligand 1 (PD-L1) plays a crucial role in tumor immune evasion, making it an important biomarker and a validated target for cancer immunotherapy. In this study, we designed, synthesized, and preclinically evaluated a series of novel PD-L1-targeted radiotracers based on a phenoxymethyl-biphenyl scaffold. Our design strategy was to incorporate different functional amino acid residues and flexible linkers between the phenoxymethyl-biphenyl scaffold and the DOTA chelator. Among the six radiotracers, [68Ga]Ga-PEG-PRO-ZB exhibited high stability, strong binding affinity to PD-L1 (KD = 19.3 ± 0.6 nM), and low nonspecific uptake. Micro-PET/CT imaging confirmed its ability to detect PD-L1 expression in multiple tumor models. Notably, [68Ga]Ga-PEG-PRO-ZB also enabled the dynamic monitoring of PD-L1 expression following immunotherapy. These results demonstrate that [68Ga]Ga-PEG-PRO-ZB can effectively visualize PD-L1 expression in vivo, offering valuable insights into the rational design and optimization of small-molecule based PD-L1 radiotracers.

The efficacy of photodynamic therapy (PDT) critically depends on the intrinsic properties of the employed photosensitizer (PS). Conventional PSs often suffer from an "always-on" characteristic, which leads to poor selectivity and undesirable phototoxicity in nontarget tissues. To address this limitation, activatable photosensitizers (aPSs) that respond selectively to disease-associated stimuli are highly desirable. Herein, we report a universal near-infrared (NIR) photosensitizing scaffold, Rho-I, for the construction of stimulus-responsive aPSs. Rho-I exhibits strong NIR absorption and high phototoxicity upon illumination, enabling efficient tumor ablation. Notably, its photodynamic activity can be effectively suppressed through phenolate donor caging. Leveraging this feature, we developed two aPSs, Rho-I-H 2 O 2 and Rho-I-ALP, which are specifically activated by hydrogen peroxide (H2O2) and alkaline phosphatase (ALP), respectively. These aPSs demonstrated selective activation and efficient photoablation of tumor cells in response to their respective stimuli. This work establishes Rho-I as a versatile scaffold for the development of precision aPSs, offering a promising strategy for targeted and safe PDT applications.

Decellularized extracellular matrix (dECM) materials are widely reported to present tissue-specific biochemical cues that influence cell behavior; here, we use porcine uterine dECM as a representative soft-tissue model to operationalize a practical digital light printing workflow. Digital light processing (DLP) offers high-fidelity, photopolymer-based fabrication that avoids shear stresses associated with extrusion and enables precise layer definition, yet its application to soft-tissue dECM remains limited. We produce and evaluate a standalone methacrylated dECM (dECM-MA) formulation and a stepwise, reproducible recipe using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and tartrazine. Histological and biochemical analyses confirm successful decellularization, substantial collagen retention, partial sGAG retention, and controlled methacrylation of accessible primary amine groups. The formulation prints via DLP to yield reproducibly defined acellular constructs at a 50-µm layer height and millimeter-scale geometries, demonstrating high dimensional fidelity and controlled swelling behavior. High resolution scanning electron microscopy (HR-SEM) imaging of printed ECM-MA and solid decellularized uterine tissue demonstrated no significant differences in porosity, pore size distribution profiles, and connectivity, as quantified by image analysis, suggesting similar capacity to support diffusion and cell penetration. In vitro studies with human uterine stromal fibroblasts-parenchymal cells of the endometrium-show surface attachment and early cell-matrix interaction on printed constructs. Together, these results establish a practical 405-nm digital light printing workflow for standalone methacrylated dECM, exemplified using uterine ECM, enabling acellular construct stereolithographic fabrication with preserved ECM features and compatibility with early cell attachment and histological processing.

Recently, it has been reported that 20% of pregnant women in the U.S. and Canada use cannabidiol (CBD) during pregnancy (Bhatia et al., 2024). The common perception is that CBD exposure is harmless to the fetus. However, the effects of CBD on the developing fetus are not well known, hampered by potential polydrug use, limited information on CBD levels in products, and varying drug administrative routes. Animal models may increase our understanding of the safety of CBD use during pregnancy. The current study exposed pregnant Sprague-Dawley rats to 50 mg/kg CBD or control vehicle once daily from gestational days 5-20. CBD was dissolved in honey and delivered via a cookie dough edible; controls received a cookie dough edible with no CBD. Exposure to CBD during gestation reduced the number of pups born and tended to increase the ratio of male-female pups by reducing the number of female pups, indicative of possible hormonal changes. Open field activity was examined in the offspring on postnatal days 30-34 (early adolescence) during the dark cycle. Prenatal CBD exposure significantly increased activity levels, impaired habituation, and increased risk-taking behavior in females, but not males. These data illustrate that prenatal CBD exposure may adversely impact behavioral development in a sex-dependent manner. Elucidation of the risks associated with CBD use during pregnancy is critical to inform pregnant women and promote healthy pregnancies.