Project Summary Cannabis is considered the most widely used psychoactive drug in the United States and all over the world. In 2020, the National Survey on Drug Use and Health (NSDUH) has reported that over 48 million Americans (~16% of the population) ages 12 and older used cannabis in the past year. This number has increased due to the expanding legalization of cannabis consumption in the US. Higher potency strains of cannabis plants have emerged over the past two decades. Unsurprisingly, adverse health outcomes associated with cannabis consumption have also been increasing. The proposed study will provide the first impact, which is the transgenerational effects of in utero and nursing cannabis vapor exposure on phenotypic defects of male and female reproductive functions. Because cannabis is a psychoactive drug, chronic or frequent use of cannabis is associated with a variety of adverse health outcomes. However, little is known about its effects on reproduction, especially the long-term consequences of cannabis on offspring and subsequent generations. To date, no systematic studies examining reproductive phenotypic defects and their associated mechanisms caused by cannabis have been performed. In addition, it is entirely unknown whether the adverse effects of cannabis on reproduction are sustained via germline transmission to subsequent generations. Therefore, this application proposes as a first step to examine the transgenerational effects of cannabis vapor exposure on male and female reproductive functions. We will characterize how cannabis vapor exposure during pregnancy and nursing affects male and female reproductive parameters in neonatal and adult testes and ovaries to understand paternally or maternally transmitted alterations in male or female germ cells. Because at least 7% of pregnant women use cannabis throughout pregnancy (~12% during the first trimester and 5.3% daily users), an appreciation of the impact of cannabis use on reproductive functions in subsequent offspring is crucial.

PROJECT NARRATIVE The overall objective of this application is to examine the transgenerational effects of in utero and nursing cannabis exposure on male and female reproductive functions. Due to the adverse effects of cannabis on human health and offspring, understanding transgenerationally inherited phenotypic defects in reproduction will provide new insights into the adverse effects of cannabis and reveal the paternal and/or maternal reproductive risks associated with cannabis use.