Two researchers in India have uncovered key molecular pathways through which chronic psychological stress undermines male fertility, shedding light on a link recognised for more than four decades but long poorly understood.

Through experiments on laboratory rats, Itishree Dubey and Sapana Kushwaha have found that stress disrupts the blood-testis barrier — an ultrathin membrane that shields developing spermatozoa from harmful substances in the blood — with the damage accumulating over weeks of sustained stress.

Their study is the first to demonstrate that chronic stress inactivates a key anchor protein in this barrier, leading to suppression of mature sperm production and potentially opening pathways towards new therapies for stress-related reproductive disorders.

“We find that the stress doesn’t act all at once — it builds up,” Kushwaha, assistant professor at the National Institute of Pharmaceutical Education and Research (NIPER) in Rae Bareli, who led the study, told The Telegraph. “The longer the stress persists, the more it weakens the protective barrier, and the machinery that produces sperm begins to fail.”

Since the 1980s, multiple studies in animals and humans have repeatedly shown that psychological stress damages sperm quality and fertility, affecting everything from sperm counts and movement to genetic quality, but the underlying molecular mechanisms have remained unclear.

Psychological stress increases stress hormones such as cortisol and leads to the build-up of oxidative stress — molecules that can harm cells and tissues — in the bloodstream. High cortisol concentrations can lower testosterone, and researchers have speculated in the past that oxidative stress could impair the sperm production machinery.

Dubey and Kushwaha exposed rats in their lab to a rotating combination of stressors, including food deprivation, temperature extremes, physical restraint and disrupted light cycles, for 8, 14 and 18 weeks. Each rat received one stressor each day. Behavioural tests showed increased anxiety, reduced exploratory behaviour, disengagement and elevated stress hormones.

In the first eight weeks, the researchers did not observe any significant changes. But as the experiments approached the 14th week, sperm count, sperm motility and sperm DNA integrity declined. Molecular analysis revealed the inactivation of proteins that maintain the blood-testis barrier and disruptions in processes that support normal sperm production.

Prolonging the stressors up to 18 weeks did not produce any further deterioration, suggesting an adaptive physiological response to persistent stress — a phenomenon in which the body adjusts to long-term challenges. The NIPER team has published its findings in the journal Reproductive Sciences.

The study also found reduced levels of irisin, a hormone present in testicular tissue, highlighting its previously underexplored role in spermatogenesis and pointing to a potential therapeutic target for stress-related infertility.

The findings, experts say, help fill a long-standing gap in understanding how psychological stress translates into biological damage.

“This study adds mechanistic insights to our knowledge of how chronic stress impacts the male reproductive system,” said Vikas Mishra, a pharmacology faculty member at Babasaheb Bhimrao Ambedkar University in Lucknow, who was not associated with the NIPER study.

“Chronic stress has an umbrella effect on human physiology — on the cardiovascular system, on the brain, on the immune system,” Mishra said. “What studies like this do is show how that damage happens, and that’s what ultimately makes treatment possible.”