Researchers in a 2023 study found that THC exposure led to decreased testicular volume, increases in sperm DNA fragmentation and alteration of the epigenome in a monkey model, which was partially reversed after THC cessation for 2 sperm cycles.
Cannabis use among reproductive-age men raises concerns about fertility and reproductive health, with inconclusive studies and limited data on its impact.
Hedges et al. (2023) used a rhesus macaque monkey model to study the impact of cannabis use on male reproductive health. A total of 6 monkeys were given daily edibles containing THC, the active ingredient in cannabis. The dosage was increased every 70 days, which is the approximate time for a sperm life cycle in macaques (and in humans), until day 210 when THC exposure was stopped:
- Low dose for days 1-70: 0.5 mg/7 kg/day.
- Moderate dose for days 71-140: 1 mg/7 kg/day.
- Heavy dose for days 141-210: 2.5 mg/7 kg/day.
After day 210 (3 sperm cycles), the researchers examined the monkeys until day 350 (for 140 days – 2 sperm cycles). They did this to see if the effects of THC on the monkeys could be reversed. They also assessed the animals before THC exposure began (pre-treatment).
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THC exposure led to altered testicular volume, hormone levels and DNA fragmentation
They found that the monkeys’ testicles decreased in volume by 59% after 210 days of THC use compared to pre-treatment. There were also decreases in the volume of the epididymis and the diameter of seminiferous tubules. The seminiferous tubules are where sperm is produced, which is stored in the epididymis before ejaculation.
After 140 days of abstinence (2 sperm cycles), testicular volume recovered to 73% of its initial size.
Hormone levels were also changed with THC exposure, which resulted in reduced testosterone and estradiol levels, with an increase in follicle-stimulating hormone levels.
In terms of semen characteristics, there was a decrease in semen volume, but no differences in sperm concentration, total sperm count, motility and morphology. DNA fragmentation was increased by up to 3.4-times in the heavy-THC dose group. DNA fragmentation levels returned to normal in all monkeys after 140 days of THC abstinence.
THC exposure led to altered protein levels in semen
The researchers examined the different semen proteins in the monkeys as these proteins can play an important role in sperm maturation, sperm-egg binding and fertilization. The researchers identified 80 proteins that showed altered expression when comparing different treatment groups (ie. moderate or heavy dose vs pre-treatment).
These 80 differently expressed proteins were found to impact pathways related to semen parameters, such as sperm concentration, count and motility. There were also an elevation in proteins related to fibrinolytic activity, which may lead to increased semen clotting that can affect fertility.
Discontinuation of THC for 140 days resulted in 60 of these 80 proteins returning to normal expression levels.
THC exposure resulted in altered epigenetic modification of DNA
An epigenetic analysis (by DNA methylation) was also performed, to evaluate what genes were being turned off due to THC exposure.
THC exposure in rhesus macaques led to altered DNA methylation in a number of genes, such as those related to neurodevelopment and sperm motility. Some of the genes that showed epigenetic alterations were involved in autism spectrum disorder, many of which (but not all) showed reversal after THC discontinuation at 140 days.
Conclusions
This study found that THC exposure in monkeys resulted in decreased testicular volume, changes in levels of hormones like testosterone and FSH, and increases in sperm DNA fragmentation.
There were also changes in protein levels in semen, which were involved in molecular pathways related to sperm concentration and motility, as well as fibrinolytic activity that can affect sperm clotting.
They also found epigenetic changes in genes involved with neurodevelopment, with some genes involved in autism spectrum disorder. Since epigenetic modifications can be inherited, it’s possible that paternal THC exposure may predispose the child to neurodevelopmental disorders.
Partial reversal of these outcomes was possible by discontinuing THC use for 2 sperm cycles (140 days).
While this research uses an animal model, monkeys represent the closest species to humans in their biology.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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