Psychoactive drugs and male fertility: impacts and mechanisms

Abstract

Although psychoactive drugs have their therapeutic values, they have been implicated in the pathogenesis of male infertility. This study highlights psychoactive drugs reported to impair male fertility, their impacts, and associated mechanisms. Published data from scholarly peer-reviewed journals were used for the present study. Papers were assessed through AJOL, DOAJ, Google Scholar, PubMed/PubMed Central, and Scopus using Medical Subjects Heading (MeSH) indexes and relevant keywords. Psychoactive drugs negatively affect male reproductive functions, including sexual urge, androgen synthesis, spermatogenesis, and sperm quality. These drugs directly induce testicular toxicity by promoting ROS-dependent testicular and sperm oxidative damage, inflammation, and apoptosis, and they also suppress the hypothalamic-pituitary-testicular axis. This results in the suppression of circulating androgen, impaired spermatogenesis, and reduced sperm quality. In conclusion, psychoactive drug abuse not only harms male sexual and erectile function as well as testicular functions, viz., testosterone concentration, spermatogenesis, and sperm quality, but it also alters testicular histoarchitecture through a cascade of events via multiple pathways. Therefore, offering adequate and effective measures against psychoactive drug-induced male infertility remains pertinent.

Keywords: Cannabis; Depressants; Drug abuse; Hallucinogens; Male infertility; Marijuana; Narcotics; Opioids; Psychoactive drugs; Stimulants.

Fig. 1

The hypothalamic-pituatary-testicular axis +  = stimulatory effect;—= inhibitory effeect. The hypothalamic-pituitary–testicular axis tightly regulates the male reproductive function. Gonadotropin releasing hormone (GnRH) is released in pulsatile manner from the hypothalamus to stimulate the release of the gonadotropins, which include the follicle stimulating hormone (FSH) and luteinizing hormone (LH). These gonadotropins stimulate the testes to maintain optimal testicular function. FSH stimulates the Sertoli cells to drive spermatogenesis, while LH stimulates the Leydig cells to promote testosterone biosynthesis, which is also required for sexual drive (libido) and spermatogenesis

Fig. 2

Effects of psychoactive drugs on sexual function and fertility indices. Psychoactive drugs usually act as stimulants or depressants irrespective of their classes. Depressants have been reported to suppress (red arrow) sexual urge, sexual and erectile function, and sexual satisfaction via downregulation of circulating androgen and stimulatory neuroendocrine like dopamine, resulting in reduced fertility indices. On the other hand, although stimulants may elicit increased (green arrow) sexual urge, sexual and erectile function, and sexual satisfactory via a testosterone-independent signaling, they also induce reduced fertility indices

Fig. 3

Effects of psychoactive drugs on testicular integrity and function. Psychoactive drugs promote increased generation of reactive oxygen species (ROS) in the testes that overwhelms the scavenging capacity of the protective testicular antioxidant system, leading to oxidative stress. These drugs also increase the accumulation of pro-inflammatory cytokines, resulting in cytokine storms. Testicular oxidative stress could be a cause and/or a consequence of the cytokine storm; this leads to a vicious cycle of oxido-inflammatory state that disrupts hypothalamic-pituitary–testicular axis and sperm integrity, resulting in altered testicular function viz. downregulation of the release of gonadotropins and testicular testosterone biosynthesis, and impaired spermatogenesis and reduced sperm quality

Fig. 4

Effect of selected psychoactive drugs on testicular histoarchitecture. A-B) Codeine-treated rabbits showed distorted testicular architecture. The seminiferous tubules showed thickened propria indicative of cessation of spermatogenesis (black arrow). There are vacuolation, sloughed germ cells, maturation arrest, and reduced mature sperm cells within the tubular lumen (red circle). There is evidence of vascular congestion (black circle and red arrow). The leydig cells appear reduced (green arrow). (Photomicrographs are from our laboratory-published: [12]. Plate C1a and 1b are the original and pseudo images respectively of the testicular histoarchitecture of vehicle-treated control rats compared with those of codeine-treated rats (C2a and 2b) showing p53 expression. Codeine treatment led to significantly increased p53 expression. Also, plate D1a and 1b are the original and pseudo images respectively of the testicular histoarchitecture of vehicle-treated control rats compared with those of codeine-treated rats (C2a and 2b) showing Bcl-2 expression. Codeine treatment led to marked reduction in Bcl-2 expression. These findings are suggestive of codeine-induced apoptosis. (Photomicrographs are from our laboratory-published: [8]. E) Rohypnol treatment led to degeneration of seminiferous tubules (black circle) and germ cells (black arrow), with widened interstitial space. (Photomicrograph is from our laboratory-In Press, [9]. F) Methamphetamine caused degeneration of germ cells and reduced mature sperm cells in the tubular lumen (black circle). It also led to vascular congestion within the interstitial space (black arrow). (Photomicrograph is from our laboratory-unpublished)