Dempsey, J. C. | Search bioRxiv

bioRxiv2026

Prenatal cannabis exposure affects human fetal neurodevelopment: anintegrated multi-omics study

Prenatal cannabis use is on the rise, and observational studies suggest that such use results in neurodevelopmental deficits in the offspring. Because observational studies can be confounded by unaccounted factors, we studied the neurodevelopmental consequences, at the molecular level, of prenatal cannabis use. We applied an integrated multi-omics approach, combining transcriptomics and global proteomics, to first trimester (T1) and second trimester (T2) human fetal brains from pregnancies with and without documented maternal cannabis exposure and no use of drugs of abuse. Prenatal cannabis exposure produced minimal molecular effects in female T1 fetal brains but induced pronounced system-level disruption in male T2 fetal brains. These disrupted pathways have molecular signatures linked to neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder, schizophrenia-related pathology, and disorders of cortical connectivity, raising significant concerns of prenatal cannabis use.

neuroscience↗

bioRxiv2025

The Impact of Delayed Evacuation on the Quality of Human Fetal Tissue

BackgroundDigoxin and other agents are frequently administered to arrest fetal circulation before the evacuation of human fetal tissue (HFT) in pregnancy terminations to address concerns about fetal viability. However, the impact of delayed evacuation on HFT quality remains unknown. Analyzing HFT is critical for diagnosing pregnancies affected by fetal abnormalities and for driving progress in biomedical research. ObjectiveThis study aims to assess the effects of delayed evacuation following fetal circulation cessation on the quality of HFT for both diagnostic and research purposes. Study DesignHFT samples were collected from second-trimester dilation and evacuation (D&E) procedures, with and without agent injection approximately 24 hours prior, as per standard care protocols. We assessed multiple parameters relevant to diagnostics and research, including: 1) cell morphology, 2) cell proliferation, 3) apoptosis, 4) cell viability in culture, and 5) nucleic acid quality. To simulate in utero conditions and determine the timeline for tissue degradation, we incubated brain tissue obtained from D&E without induced demise at 37{degrees}C for up to 18 hours. ResultsWe analyzed 18 HFT samples from D&E procedures performed 19-25 hours after digoxin or potassium chloride (KCl) injection and compared them to 26 HFT samples from immediate evacuations without prior injection. Induced fetal demise resulted in 1) disrupted cell morphology, 2) decreased cell proliferation, 3) increased apoptosis, 4) reduced cell viability in culture, and 5) lower RNA quality. Despite these findings, all samples yielded DNA of sufficient quality for polymerase chain reaction (PCR). ConclusionD&E procedures performed after fetal demise induced by digoxin or KCl lead to decreased HFT quality, limiting its diagnostic and research potential beyond gross tissue evaluation and DNA extraction. Limiting the time between fetal circulation arrest and evacuation may improve HFT quality for clinical and research applications.

pathology↗