Prenatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters the Expression of miR-122-5p and Its Target Igf1r in the Adult Rat Ovary

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 t...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-07, Vol.23 (14), p.8000
Main Authors: Martínez-Peña, Annia A., Lee, Kendrick, Pereira, Madison, Ayyash, Ahmed, Petrik, James J., Hardy, Daniel B., Holloway, Alison C.
Format: Article
Language:English
Subjects:
Apoptosis
Cannabis
Cell growth
DNA methylation
Epigenetics
Explants
Exposure
Fertility
Fetuses
Gene expression
Granulosa cells
Growth factors
Industrialized nations
Insulin
Insulin-like growth factors
Long-term effects
Marijuana
MicroRNAs
miRNA
Ovarian cancer
Ovaries
Pregnancy
Prenatal experience
Prenatal exposure
Reproductive health
Senescence
Tetrahydrocannabinol
THC
Womens health
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23148000