HMN 2025: How Omega-3 fatty acid DHA shown to relax reproductive tract muscle

A research team has discovered that docosahexaenoic acid (DHA), a major omega-3 fatty acid found in fish oil, directly relaxes smooth muscle in the male reproductive tract by blocking specific calcium channels.

The findings, published in Biological and Pharmaceutical Bulletin, may help explain DHA’s broader health benefits and suggest potential new approaches to treating male infertility.

The team, from the Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, including Associate Professor Keisuke Obara, Lecturer Kento Yoshioka, and Professor Yoshio Tanaka, studied how DHA affects the vas deferens, a muscle that propels sperm during ejaculation. Normally, the hormone noradrenaline causes this muscle to contract strongly.

DHA was found to significantly reduce these contractions by inhibiting TRPC3/6 channels, which allow calcium ions to enter muscle cells and trigger tightening. Interestingly, DHA did not reduce contractions in the prostate, suggesting that its action is selective to tissues where TRPC3/6 channels are abundant.

By lowering the pressure inside the vas deferens, DHA might ease sperm passage in men with ejaculatory duct obstruction, a known cause of infertility.

Broader significance

DHA has long been associated with brain health, anti-inflammatory effects, and cardiovascular protection. This study provides new evidence that DHA’s benefits extend to reproductive health, by acting directly on the molecular machinery that controls smooth muscle contraction.

“Our results suggest TRPC3/6 channels as new molecular targets of DHA,” said Dr. Keisuke Obara, lead author and Associate Professor at Toho University.

“This not only gives us a clearer understanding of how omega-3 fatty acids work in the body, but also highlights their potential for improving male reproductive health.”

The researchers note that further studies are needed to confirm these findings in clinical settings. Still, the concentrations of DHA used in their experiments are comparable to levels achieved through dietary supplementation, suggesting real-world relevance.

Proposed mechanism

Noradrenaline (NA) activates ?_1A-adrenoceptors (?_1A-AR), driving Ca²⁺ entry through two pathways that promote contraction: L-type voltage-dependent Ca²⁺ channels (L-type VDCC) and TRPC3/6 channels.

Acute application of docosahexaenoic acid (DHA) preferentially suppresses the TRPC3/6-mediated component (blue block), thereby reducing the residual “fast/phasic” portion of the NA-evoked contraction even when L-type channels are blocked.

The net effect is diminished Ca²⁺ influx and attenuation of rat vas deferens smooth muscle contraction.

The content is provided for information purposes only.