Exosomes-mediated retinoic acid disruption: A link between gut microbiota depletion and impaired spermatogenesis.

Toxicology

College of Animal Sciences, Jilin University, No. 5333 Xi'an Road, Lvyuan District, Changchun, Jilin 130062, China. Electronic address:

Published: November 2024

AI Article Synopsis

  • - The gut microbiota plays a crucial role in regulating male reproductive health, but factors like antibiotics can disrupt this balance and lead to reproductive issues.
  • - In a study using a mouse model, researchers found that antibiotic-induced depletion of gut microbiota resulted in reduced sperm count and germ cells in the testes, linked to molecular changes.
  • - The findings suggest a new pathway involving gut microbiota, exosomes, and retinoic acid, where gut dysbiosis disrupts retinoic acid levels and impairs sperm production by affecting meiosis.

Article Abstract

Gut microbiota symbiosis faces enormous challenge with increasing exposure to drugs such as environmental poisons and antibiotics. The gut microbiota is an important component of the host microbiota and has been proven to be involved in regulating spermatogenesis, but the molecular mechanism is still unclear. A male mouse model with gut microbiota depletion/dysbiosis was constructed by adding combined antibiotics to free drinking water, and reproductive parameters such as epididymal sperm count, testicular weight and paraffin sections were measured. Testicular transcriptomic and serum metabolomic analyses were performed to reveal the molecular mechanism of reproductive dysfunction induced by gut microbiota dysbiosis in male mice.This study confirms that antibiotic induced depletion of gut microbiota reduces sperm count in the epididymis and reduces germ cells in the seminiferous tubules in male mice. Further study showed that exosomes isolated from microbiota-depleted mice led to abnormally high levels of retinoic acid and decrease in the number of germ cells in the seminiferous tubules and sperm in the epididymis. Finally, abnormally high levels of retinoic acid was confirmed to disrupted meiotic processes, resulting in spermatogenesis disorders. This study proposed the concept of the gut microbiota-exosome-retinoic acid-testicular axis and demonstrated that depletion of the gut microbiota caused changes in the function of exosomes, which led to abnormal retinoic acid metabolism in the testis, thereby impairing meiosis and spermatogenesis processes.

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Source
http://dx.doi.org/10.1016/j.tox.2024.153907DOI Listing

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