Document Type
Article
Publication Date
July 2022
Journal
International Journal of Molecular Sciences
Volume
23
First Page
8000
URL with Digital Object Identifier
10.3390/ijms23148000.
Abstract
As cannabis use during pregnancy increases, it is important to understand its effectson the developing fetus. Particularly, the long-term effects of its psychoactive component, delta-9-tetrahydrocannabinol (THC), on the offspring’s reproductive health are not fully understood.This study examined the impact of gestational THC exposure on the miRNA profile in adult ratovaries and the possible consequences on ovarian health. Prenatal THC exposure resulted in thedifferential expression of 12 out of 420 evaluated miRNAs. From the differentially expressed miRNAs,miR-122-5p, which is highly conserved among species, was the only upregulated target and hadthe greatest fold change. The upregulation of miR-122-5p and the downregulation of its targetinsulin-like growth factor 1 receptor (Igf1r) were confirmed by RT-qPCR. Prenatally THC-exposedovaries had decreased IGF-1R-positive follicular cells and increased follicular apoptosis. Furthermore,THC decreased Igf1r expression in ovarian explants and granulosa cells after 48 h. As decreasedIGF-1R has been associated with diminished ovarian health and fertility, we propose that theseTHC-induced changes may partially explain the altered ovarian follicle dynamics observed in THC-exposedoffspring. Taken together, our data suggests that prenatal THC exposure may impact key pathways in the developing ovary, which could lead to subfertility or premature reproductive senescence.