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- W4387396541 abstract "Cannabis is the most commonly used illicit drug by reproductive age males and emerging evidence suggests it may impact fertility. Our objective was to determine the effect of chronic delta-9-tetrahydrocannabinol (THC) use on the sperm epigenome and whether these changes are permanent with THC cessation in a rhesus macaque (RM) model. Prior studies have linked sperm DNA methylation alterations with impaired spermatogenesis and infertility. We performed whole genome bisulfite sequencing (WGBS) of DNA extracted from sperm collected from 6 adult RM at baseline (pre-THC), at a high-THC dose (2.5mg/7kg/day), and post-THC discontinuation for 140 days (∼2 spermatogenesis cycles). Overlap of genes annotated to differentially methylatedregions (DMRs) in our RM following THC with published gene lists of human cannabis users and non-users was more than expected by chance (p= 1.7e-13). Pre-THC vs post-THC DMRs were similarly enriched for genes annotated to methylation differences between pre-cannabis exposure vs. post-cannabis discontinuation in humans. We identified 1,613 DMRs between pre-THC and heavy-THC that intersected DMRs in heavy-THC versus post-THC sperm samples and demonstrated a reversal in methylation post-THC toward the level of methylation pre-THC. Genes annotated to a smaller number of DMRs (1,601) between pre-THC and heavy-THC did not return to baseline levels after the THC washout period. Both the restored and non-restored DMRs were highly enriched for genes in the “synaptogenesis signaling pathway” (e.g., BDNF, several integrin, glutamate receptor, and synapsin genes), as well as for genes in the “sperm motility” canonical pathway (e.g., ADCY10, CNG, and PLA2). From the literature we identified 217 genes reported to play a key role in male infertility, of which 55 were differentially methylated with THC. We highlight a subset of these THC-DMRs in Table 1. Chronic THC use in RM alters genes related to several key regulatory pathways including fertility. Discontinuation of THC restored methylation in only a subset of DMRs." @default.
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- W4387396541 date "2023-10-01" @default.
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- W4387396541 title "DELTA-9-TETRAHYDROCANNABINOL EXPOSURE ALTERS SPERM DNA METHYLATION IN RHESUS MACAQUES" @default.
- W4387396541 doi "https://doi.org/10.1016/j.fertnstert.2023.08.409" @default.
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