Reproductive Toxicity Assessment of Origanum vulgare Essential Oil on Male Wistar Rats

Background: The oregano essential oil (Origanum vulgare L.) is rich in phenolic compounds with therapeutic actions such as antimicrobial, antifungal and antioxidant. Based on the therapeutic potential and clinical use of oregano essential oil, in vivo toxicology studies of oregano essential oil are scarce and the current researches focus on the genotoxicity of several species of oregano; however, toxicological and complementary studies are needed to ensure safety of formulations containing this oil. Through values of Minimum Inhibitory Concentration (MIC) of oregano essential oil against Candida species, and increased in an exponential scale, the initial dose was obtained. This study aims to evaluate male fertility through the reproductive aspects of rats chronically treated with oregano essential oil. Materials, Methods & Results: The rats were divided into five groups with 10 males and 30 females each; three groups were treated with oregano essential oil at a concentration of 3% Vol/Vol (GO3%), of 9% Vol/Vol (GO9%) and of 27% Vol/ Vol (GO27%). The negative control group received the vehicle, 0.001% Vol/Vol Tween 80 (GC-) and the positive control group was treated with thymol and terpinen-4-ol, at the same concentration found in the oregano essential oil, detected by gas chromatography (3% + 3% Vol/Vol) (GC+). Animals were allowed to adapt for at least ten days before the beginning of the experiment. They were maintained under controlled temperature (± 22oC), 50% ± 5 relative humidity and lighting conditions (12 L, 12 D photoperiod) and had free access to food and water. All animals were treated daily by gavages. Male rats were treated for 91 days (70 days before mating and 21 during mating) and females were treated before mating (14 days) and during mating (21 days), pregnancy (21 days), and lactation periods (21 days). The reproductive variables were evaluated: the total number of sperm cells, daily sperm production, sperm morphology, serum testosterone dosage, organ histopathology and animal growth were evaluated. The results showed that the essential oil of oregano interfered decreasing the number of sperm cells, the total number of sperm stored in the epididymis tail and serum testosterone levels (P < 0.05), in the sperm morphology in the oil increased the percentage of sperm malformations in the treated groups, dose dependent manner, also in the positive control (P < 0.001). Discussion: The Origanum vulgare L. essential oil, as well as other essential oils, has potential to be used in the development of new drugs as recent researches claim. However, the essential oil acted directly on sexual organs, reducing their weight and causing tissue injury of the testes. At the highest dose, these changes may be associated with metabolic disorders, as testosterone levels are also decreased. The direct action of oregano essential oil at the highest dose (27% Vol/Vol) on the testicle is also responsible for the reduction in sperm concentration and production of abnormal gametes. It may also play an adverse role on the Leydig cell, affecting testosterone production. These outcomes corroborate the results of other essential oils. The oregano essential oil, only at the highest tested dose and its positive control (3% / 3% Vol/Vol), compared to a negative control, interfered in sperm and hormonal parameters evaluated, causing infertility in male Wistar rats under the conditions tested.