Effects of paternal exposure to delta-9 tetrahydrocannabinol (THC) on paternal reproductive tissue and overall health of offspring in medaka, Oryzias latipes

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Yashi Feng (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Ramji Bhandari

Abstract: After the legalization of marijuana for recreational and medicinal use in the United States, more and more young adults of child-bearing age have legal access to it. Marijuana has been found to cause neurological, respiratory, urogenital, reproductive and immune health abnormalities. Despite its adverse health outcomes, research also suggests that cannabinoids, chemical constituents of marijuana may be useful for the treatment of pain, nausea, epilepsy, obesity, and several human health conditions. Delta-9 tetrahydrocannabinol (?9-THC), which is one of the psychoactive constituents of marijuana, can induce epigenetic alterations (epimutations) on genome DNA of gametes due to chronic paternal consumption. Nevertheless, it has not been experimentally demonstrated yet whether the marijuana-induced alterations in the germline epigenome can be passed onto the offspring causing transcriptional profiles of abnormal health phenotypes. The present study, therefore, examined pre-conceptional paternal (F0) THC exposure effects on epigenome of the paternal germline and transcriptional profiles of the derived male offspring (F1). Hypotheses tested that 1) THC induces transcriptional alterations in the testis and epigenetic aberrations in the germline of exposed father; 2) the offspring born with the THC-exposed father exhibit transcriptional alterations in various somatic tissues indictive of adverse health conditions. Reproductively active male medaka fish were exposed to four different concentrations of THC (0, 30, 120, 600 ug/L) for 21 days and their fertilization efficiency was determined, including epigenetic profile of their sperm and transcriptome profile of the derived offspring. Paternal THC exposure reduced fertilization efficiency of the F0 father and F1 derived offspring. Direct THC exposure resulted in differentially expressed genes (DEGs) related to metabolism, neuron-specific RNA splicing mechanism, and myocyte formation in the father’s testis, while DEGs mainly related to metabolism, neuron signaling, and immune system were found in F1 somatic tissues. Differentially methylated regions (DMRs) in F0 sperm predicted dysregulation in F1 transcriptome profile. Molecular changes observed in the present study suggest effects of paternal THC exposure on their fertility and offspring reproductive and metabolic health. [This abstract has been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]

Additional Information

Language: English
Date: 2021
Cannabinoids, Epigenetics, THC
Oryzias latipes

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