دورية أكاديمية
أعرض في EDS

DNA methylation, but not microRNA expression, is affected by in vitro THC exposure in bovine granulosa cells.

التفاصيل البيبلوغرافية
العنوان: DNA methylation, but not microRNA expression, is affected by in vitro THC exposure in bovine granulosa cells.
المؤلفون: Floccari S; Reproductive Health and Biotechnology Lab, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Sabry R; Reproductive Health and Biotechnology Lab, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Choux L; Reproductive Health and Biotechnology Lab, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada., Neal MS; ONE Fertility, Burlington, ON, Canada.; Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada., Khokhar JY; Department of Anatomy and Cell Biology, Western University, London, ON, Canada., Favetta LA; Reproductive Health and Biotechnology Lab, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada. lfavetta@uoguelph.ca.
المصدر: BMC pharmacology & toxicology [BMC Pharmacol Toxicol] 2024 Jul 15; Vol. 25 (1), pp. 42. Date of Electronic Publication: 2024 Jul 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101590449 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-6511 (Electronic) Linking ISSN: 20506511 NLM ISO Abbreviation: BMC Pharmacol Toxicol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central
مواضيع طبية MeSH: MicroRNAs*/genetics , Dronabinol*/pharmacology , Granulosa Cells*/drug effects , Granulosa Cells*/metabolism , DNA Methylation*/drug effects, Animals ; Female ; Cattle ; Cells, Cultured
مستخلص: Background: A global increase in cannabis use has led to questions about its effects on fertility. The rise in consumption amongst women of reproductive age is a growing concern, as this group is vulnerable in terms of reproductive health. Ample evidence suggests that the psychoactive component of cannabis, Δ 9 -Tetrahydrocannabinol (THC), interacts with the endocannabinoid system (ECS), that helps regulate mammalian reproduction. This study aimed to research the epigenetic effects of THC in bovine granulosa cells (GCs) by (1) investigating global DNA methylation via measuring 5-mC and 5-hmC levels; (2) measuring key methylation regulators, including the methylating enzymes DNMT1, DNMT3a, DNMT3b and the demethylases TDG and TET1/2/3; and (3) assessing fertility-associated miRNAs key in developmental competency, including miR-21, -155, -33b, -324 and -346.
Methods: Bovine GCs were used as a translational model for reproductive toxicity in humans. To determine THC effects, GCs were isolated from Cumulus-Oocyte-Complexes (COCs) from bovine ovaries, cultured in vitro for 7 days, or until confluent, and cryopreserved at passage 1 (P1). For experimentation, cells were thawed, cultured until passage 2 (P2), serum restricted for 24-h and treated for 24-h in one of five groups: control, vehicle (1:1:18 ethanol: tween: saline) and three clinically relevant THC doses (0.032, 0.32 and 3.2 μM). Global methylation was assessed by measuring 5-mC and 5-hmC levels with flow cytometry. To assess mRNA and protein expression of methylation regulators and miRNA profiles, qPCR and Western Blotting were utilized. Shapiro-Wilk test was used to determine normality within datasets. One-way ANOVA was applied to determine statistical significance using GraphPad Prism 6.0.0.
Results: Results indicate a significant decrease (p = 0.0435) in 5-mC levels following low THC exposure, while no changes were observed in 5-hmC levels. A significant increase in DNMT1 following high THC exposure at the RNA level (p < 0.05) and a significant increase following low THC exposure at the protein level (p = 0.0048) were also observed. No significant differences were observed in DNMT3a/3b, TDG, TET1/2/3 mRNAs or in any of the miRNAs analyzed.
Conclusions: This research suggests that THC mainly affects DNA methylation, but not miRNA profiles, ultimately altering gene expression and likely impairing oocyte competence, maturation, and fertilization potential.
(© 2024. The Author(s).)
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معلومات مُعتمدة: N/A Ontario Veterinary College Scholarship; N/A Ontario Graduate Scholarship; 072049 General Purpose Grant, Department of Biomedical Sciences, University of Guelph
فهرسة مساهمة: Keywords: Cannabis; DNA methylation; Fertility; Granulosa cells; MicroRNAs; THC
المشرفين على المادة: 0 (MicroRNAs)
7J8897W37S (Dronabinol)
تواريخ الأحداث: Date Created: 20240715 Date Completed: 20240716 Latest Revision: 20240717
رمز التحديث: 20240717
مُعرف محوري في PubMed: PMC11247865
DOI: 10.1186/s40360-024-00763-5
PMID: 39010179
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-6511
DOI:10.1186/s40360-024-00763-5