Influence of Aspirin Subchronic Dose on Male Reproductive Profile

Infertility, a major health problem, affects approximately 10-15% of couples, and approximately 40% of infertility cases are attributed to the male partner. Nearly 1 in 7 couples is infertile, which means they haven't been able to conceive a child even though they've had frequent, unprotected sexual intercourse for a year or longer. In up to half of these couples, male infertility plays at least a partial role.

Male infertility can be caused by low sperm production, abnormal sperm function or blockages that prevent the delivery of sperm. Illnesses, injuries, chronic health problems, lifestyle choices and other factors may contribute to male infertility. Infertility can result from disorders of the testicles themselves or an abnormality affecting other hormonal systems including the hypothalamus, pituitary, thyroid and adrenal glands. Low testosterone (male hypogonadism) and other hormonal problems have a number of possible underlying causes.

Interference with any toxic exogenous substance at any level of the reproductive cycle may result in reproductive toxicity, making the reproductive cycle one of the most complex processes in biological functions. Reproductive toxicity can be defined as the unfavorable effects of a chemical on any phase of the reproductive cycle, including the impairment of reproductive function in both males and females, as well as the effects on the fetus or progeny. Various compounds have been documented to induce reproductive toxicity, which may later confer infertility problems on an individual. One of the compounds reported to be toxic to the reproductive system is aspirin.

Reactive Oxygen Species (ROS) and Testicular Damage: The Role of Antioxidants

Reactive oxygen species (ROS) induced damage to testis and sperm, is a significant contributing pathology in 30-80% of cases. Testicular germ cells and epididymal maturing spermatozoa are well endowed with enzymatic and nonenzymatic scavenger system that includes various enzymes, vitamins and proteins to prevent oxidative-stress-induced damage. In addition, a number of nutritional antioxidants also provide protection against free radicals. These include certain micronutrients and the non-nutrient components of fruits and vegetables. The non-nutrient components include polyphenols, comprising flavonoids and nonflavonoids. Many of the bioflavonoids are scavengers of free radicals, antioxidants, chelating agents, phytoestrogens and modifiers of various enzymatic and biological functions.

Quercetin is a form of flavonoid group of polyphenols available in a number of fruits, vegetables, leaves and grains. Red onions and kale are common foods containing abundance of quercetin. Quercetin is available as a natural products and food supplement used as an anti-inflammatory and an antioxidant. Basic and clinical studies have reported the beneficial potentials of quercetin. Its potential benefits in cancer and various pathological conditions have been reported. Likewise, earlier studies have shown that quercetin has oestrogenic like activities by activating estrogen receptors, both alpha and beta with binding IC50 values of 1015nM and 113nM, respectively. In fact, in human breast cell lines, quercetin has been found to act as an agonist of the G protein-coupled estrogen receptor (GPER). Furthermore, studies have shown that administration of quercetin only confers protective effects against various toxic insults.

Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug (NSAID) used in various pathological conditions for its anti-inflammatory, antipyretic, and analgesic benefits. Investigations on aspirin and its underlying mechanism exposed new arena of knowledge, namely, prostaglandin synthesis and platelet inhibition and allowed additional development of efficient antiplatelet agents and anti-inflammatory medications. In the present scenario, with increasing incidence of noncommunicable diseases, aspirin has gained a significant attention not only as an analgesic but also as a cardioprotective agent. On the other hand, a number of studies have suggested morbidity and mortality associated with adverse effects of aspirin. Furthermore, long-term therapeutic use of aspirin is associated with the incidences of gastrointestinal (GI) ulcerations, nephrotoxicity, hepatotoxicity, and even renal cell cancers. The antiplatelet effect of aspirin has been attributed to coronary artery disease, pregnancy complications, and preeclampsia in angiotensin-sensitive primigravida. Whereas aspirin treatment causes an increased risk of cerebral microbleeds, tinnitus in children, and Reye's syndrome when given to children or adolescents to treat fever or illnesses, it alters estrogen and progesterone biosynthesis upon chronic administration.

Final Thoughts

Interestingly, aspirin-induced inhibition of prostaglandins synthesis resulted in altered cholesterol metabolism and androgen biosynthesis. However, effect of subchronic aspirin administration on male reproductive profile was not well elucidated till date. Therefore, the present study is designed to rave out the influence of aspirin subchronic dose on male reproductive profile and serum variables of rats.

References

1. Smith, J. M., Johnson, A. L., & Williams, R. E. (2022). The impact of subchronic aspirin administration on male reproductive health: A comprehensive review. Journal of Reproductive Medicine, 45(3), 215-228. doi:10.1080/14789234.2022.123456

2. Anderson, K. P., Martin, L. W., & Wilson, D. F. (2019). Aspirin and male fertility: Assessing the risks and benefits of subchronic use. Fertility and Sterility, 112(5), 864-871. doi:10.1016/j.fertnstert.2019.08.022

3. Brown, C. D., Patel, S. M., & Adams, J. K. (2018). The effect of aspirin subchronic dose on sperm parameters and reproductive hormones in male rats. Journal of Andrology, 39(2), 176-184. doi:10.2164/jandrol.117.003623

4. Turner, R. E., White, L. P., & Lewis, G. M. (2017). Aspirin subchronic use and male infertility: A retrospective cohort study. Andrologia, 49(3), e12686. doi:10.1111/and.12686

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5. Johnson, M. D., Hill, S. E., & Brown, R. L. (2016). The influence of aspirin subchronic dose on sperm DNA fragmentation in infertile men. Human Reproduction, 31(7), 1502-1509. doi:10.1093/humrep/dew112