Sesame Oil and Alpha-Lipoic Acid Shield Rat Testes from Heat Damage

Chronic scrotal heat exposure wrecked the fertility of laboratory rats — and a simple combination of two antioxidant supplements, sesame seed oil and alpha-lipoic acid, largely put the damage back together. That is the central finding of a new animal study published in the journal Basic and Clinical Andrology, in which researchers at Urmia University in Iran showed that the paired supplements outperformed either compound alone at protecting sperm quality, testicular tissue, and breeding outcomes from the oxidative assault of repeated overheating. The work is a rodent experiment, not a human trial, and its authors are careful to say that clinical translation will require further study.

The experimental setup was deliberately harsh. Thirty male Wistar rats, aged twelve to fourteen weeks, were divided into five groups of six. A control group received saline and was anesthetized with xylazine while its lower body was dipped in a 22-degree Celsius water bath. The heat-stressed group underwent the same routine, but in water held at 43 degrees Celsius for twenty minutes a day, every day, for sixty days — a duration chosen to match the full spermatogenic cycle in rats. Three further groups endured the identical heat protocol while receiving daily supplements: alpha-lipoic acid at 100 milligrams per kilogram, sesame seed oil at 5 milliliters per kilogram, or both together. The heat model was adapted from earlier work on scrotal hyperthermia, and the team notes that the design mirrors clinical situations in which testicular temperature rises, including varicocele, occupational heat exposure among welders and bakers, cryptorchidism, febrile illness, and lifestyle factors such as prolonged sitting or tight clothing.

Sixty days of near-daily scorching took a measurable toll. Epididymal sperm concentration collapsed from 86.9 million per milliliter in controls to 33.1 million in the heat-stressed group. Total motility fell from 92.0 percent to 44.1 percent, average path velocity dropped from 119.4 to 68.0 micrometers per second, and straightness declined from 84.5 to 51.4 percent, all differences reaching statistical significance. Plasma membrane functionality, assessed with a hypoosmotic swelling test, fell from 78.3 percent to 43.4 percent. DNA damage, measured by acridine orange staining, jumped more than fivefold, from 5.1 percent to 27.8 percent. Abnormal sperm morphology increased, viability declined, and the testes themselves shrank, dropping from an average of 1.8 grams to 1.2 grams, with epididymal weight falling in parallel.

The biochemical signature of the injury pointed squarely at oxidative stress. Total antioxidant capacity in testicular tissue fell from 2.6 to 1.1 millimoles per gram of protein, while the activities of the antioxidant enzymes glutathione peroxidase, catalase, and superoxide dismutase all dropped by roughly half. Glutathione, a key cellular antioxidant, was depleted from 31.3 to 15.0 nanomoles per milligram of protein. Meanwhile, malondialdehyde, a marker of lipid peroxidation, more than tripled, and nitric oxide levels more than doubled. Heat also shifted the apoptotic balance: the pro-apoptotic genes Bax, caspase-3, and caspase-9 were upregulated 3.5-, 4.2-, and 3.8-fold respectively, while the anti-apoptotic Bcl-2 was downregulated to 0.4-fold of control levels. Under the microscope, the damage was severe, scoring at the worst grade of the Cosentino histopathology scale, and the mean Johnsen score, a measure of spermatogenic integrity, sank to 3.2 compared with 9.5 in controls.

Against this backdrop, both supplements produced substantial — and partially complementary — rescue. Alpha-lipoic acid alone restored sperm concentration and motility toward control values, cut DNA damage to 12.0 percent, and lifted histopathology to Cosentino grade 2 with a Johnsen score of 7.1. Sesame seed oil performed comparably, reducing DNA damage to 11.5 percent and achieving a Johnsen score of 7.0. But the combination was consistently the strongest performer: sperm concentration reached 77.5 million per milliliter, DNA damage fell to 7.4 percent, membrane functionality returned to 78.4 percent — essentially matching unheated controls — and testicular histology improved to Cosentino grade 1 with a Johnsen score of 8.8. Antioxidant enzymes and total antioxidant capacity rebounded, malondialdehyde fell back to 1.5 nanomoles per gram of protein, and the apoptotic gene profile normalized, with Bax expression down to 1.2-fold and Bcl-2 nearly restored.

The most striking differences emerged in the histological and fertility endpoints. Indices of spermatogenesis — the spermiogenesis index, Sertoli cell index, meiotic index, tubular differentiation index, repopulation index, and Leydig cell nuclear density — all collapsed under heat stress and recovered most fully in the combination group. The spermiogenesis index, for example, fell from 95 percent in controls to 45 percent under heat stress before climbing back with treatment. When each male rat was mated naturally with an untreated female, the consequences of heat exposure became stark: the pregnancy index halved to 50 percent, the fertility index dropped to 40 percent, and implantation sites per female fell from 10.1 to 5.2. In the combination group, the pregnancy index rebounded to 90 percent and the fertility index to 85 percent, with single-treatment groups improving less dramatically.

Why should two antioxidants work better together than apart? The authors argue that the compounds operate on different fronts. Alpha-lipoic acid, a mitochondrial organosulfur compound that serves as a cofactor in energy-metabolism enzyme complexes, scavenges superoxide, hydroxyl, and peroxyl radicals, regenerates other endogenous antioxidants, and helps recycle glutathione through its reduced form, dihydrolipoic acid. Sesame seed oil brings its own arsenal: the lignans sesamin, sesamol, and sesaminol, along with tocopherols, phenolics, and flavonoids, which neutralize radicals and damp inflammatory nitric oxide production, plus a lipid profile rich in oleic and linoleic acids. The researchers suggest that alpha-lipoic acid acts mainly inside cells while sesame oil’s components protect at membranes and in the extracellular environment, a division of labor that could explain the synergy seen across sperm parameters, oxidant markers, gene expression, and tissue architecture.

The study is not without caveats, and the authors enumerate them candidly. The xylazine anesthesia required for the daily water-bath protocol has hyperglycemic and cardiovascular effects that could themselves alter oxidative markers, confounding the results. Water intake was not monitored, and because heat-stressed rats drink more, the alpha-lipoic acid dose delivered through drinking water may have varied between animals. The fertility assays, with only six males per group, were underpowered — the authors report a statistical power of roughly 0.5 for those endpoints despite unusually strong p-values — and rodent thermoregulation differs substantially from that of humans, limiting direct translation. The team calls for anesthesia-free heat models, monitored dosing, larger cohorts, and eventual clinical trials before sesame oil and alpha-lipoic acid could be recommended as adjunct therapies for heat-related male subfertility.

Those limitations aside, the study adds weight to a growing body of evidence that oxidative stress is the pivotal mechanism linking testicular heat to infertility, and that layered antioxidant defenses may be more effective than any single compound. For men whose fertility is threatened by varicocele, occupational heat, fever, or lifestyle-related scrotal warming, the prospect of a low-cost, food-derived protective combination is tantalizing. But the findings so far live entirely in rats overheated under laboratory conditions. Until human studies confirm that the same synergy holds at safe, standardized doses, sesame oil and alpha-lipoic acid remain promising laboratory allies against heat — not yet a prescription.

Subject of Research: Antioxidant protection against heat stress-induced testicular injury and infertility in male rats

Article Title: Synergistic amelioration of heat stress-induced testicular damage and impaired fertility by sesame seed oil and α-lipoic acid in male rats

Article References: Hashemi, A., Soleimanzadeh, A., Ayen, E., Razi, M., & Keshipour, H. (2026). Synergistic amelioration of heat stress-induced testicular damage and impaired fertility by sesame seed oil and α-lipoic acid in male rats. Basic and Clinical Andrology, 36(1), Article 14. https://doi.org/10.1186/s12610-026-00306-4

Image Credits: AI Generated

DOI: 10.1186/s12610-026-00306-4

Keywords: heat stress, male infertility, sesame seed oil, alpha-lipoic acid, oxidative stress, sperm quality, testicular histology, apoptosis, rats, antioxidants, fertility, reproductive biology