Article
Prenatal Exposure to Delta-9-tetrahydrocannabidinol (THC) Alters the Expression of miR-122-5p and Its Target Igf1r in the Adult Rat Ovary
International Journal of Molecular Sciences
(2022)
Abstract
As cannabis use during pregnancy increases, it is important to understand its effects
on 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 rat
ovaries and the possible consequences on ovarian health. Prenatal THC exposure resulted in the
differential 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 had
the greatest fold change. The upregulation of miR-122-5p and the downregulation of its target
insulin-like growth factor 1 receptor (Igf1r) were confirmed by RT-qPCR. Prenatally THC-exposed
ovaries 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 decreased
IGF-1R has been associated with diminished ovarian health and fertility, we propose that these
THC-induced changes may partially explain the altered ovarian follicle dynamics observed in THC-exposed
offspring. 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.
Keywords
- cannabis,
- THC,
- ovary,
- microRNAs,
- IGF1R,
- DOHaD;
Disciplines
Publication Date
July 20, 2022
DOI
10.3390/ijms23148000.
Citation Information
Daniel B Hardy, Kendrick Lee, James J Petrol and Alison C Holloway. "Prenatal Exposure to Delta-9-tetrahydrocannabidinol (THC) Alters the Expression of miR-122-5p and Its Target Igf1r in the Adult Rat Ovary" International Journal of Molecular Sciences Vol. 23 (2022) p. 8000 Available at: http://works.bepress.com/daniel-hardy/29/