Nicotine Diminishes Testicular Gametogenesis, Steroidogenesis, and Steroidogenic Acute Regulatory Protein Expression in Adult Albino Rats: Possible Influence on Pituitary Gonadotropins and Alteration of Testicular Antioxidant Status

Abstract

The present study was done to evaluate the pituitary-testicular activities of rats subjected to chronic nicotine treatment. The testicular key androgenic enzymes activities, plasma and intratesticular testosterone (ITT) concentrations, and plasma concentration of gonadotropin were significantly reduced by nicotine treatment along with the decreased sperm counts and the disruption of spermatogenesis indicated by significant reduction in the number of different generations of germ cells at stage VII of the spermatogenesis cycle with increased sperm head abnormalities. The Western blot and the reverse transcriptase-PCR analysis revealed that the nicotine induced a marked decrease in the expression of testicular steroidogenic acute regulatory (StAR) protein, which helps in the transfer of cholesterol in mitochondria for the testosterone biosynthesis. The increased testicular lipid peroxidation, plasma concentration of corticosterone, with enhanced hydrogen peroxide and hydroxyl radical generations, as well as decreased glutathione level, reduced antioxidant enzymes activities, and mitochondrial membrane potential (Deltapsi(m)) of testis, were noted after nicotine treatment in rats. Human chorionic gonadotropin or taurine supplementation with nicotine prevented the degeneration of germ cells to some extent, restored spermatogenesis moderately with decreased sperm head abnormalities, and enhanced sperm counts, accompanied with increase in plasma and ITT concentrations, testicular StAR gene expression, and key androgenic enzymes activities. Moreover, taurine supplementation to nicotine-treated animals resulted in the diminution of testicular lipid peroxidation, hydrogen peroxide and hydroxyl radical generations, with the elevation in glutathione level as well as different antioxidant enzymes activities and Deltapsi(m) in testis. The results indicated that nicotine caused testicular toxicity by germ cell degeneration, inhibition of StAR gene expression along with androgen production in adult male rats probably by affecting pituitary gonadotropin, and/or modulating the extent of testicular antioxidant status.

Environmental Toxicants Induced Male Reproductive Disorders: Identification and Mechanism of Action

“…Similarly, the notion that all EDCs act by mimicking oestrogen (environmental oestrogens) is too simplistic. The current literature illustrates that EDCs can act as oestrogens, anti-oestrogens, anti-androgens, steroidogenic enzyme inhibitors and can also act via interaction with the thyroid hormones and their receptors, or within the brain and the hypothalamo-pituitary axis, as well as the immune system (Fisher, 2004;Jana et al, 2006;2010a). Reports of declining sperm counts over the past 50 years and other disturbing trends alerted scientists to the possibility that exposure to chemicals in the environment may damage male reproductive health (Carlsen et al, 1992).…”

Adverse effects of perinatal nicotine exposure on reproductive outcomes

“…There is considerable evidence from animal studies that perinatal exposure to nicotine results in oxidative stress and/or decreased antioxidant potential in the offspring (Bruin et al 2008, Xiao et al 2011, Conceicao et al 2015, suggesting that increased oxidative stress may be a potential mechanism underlying deleterious nicotine-induced reproductive outcomes. Indeed, adult animals exposed to nicotine exhibited increased ROS production and oxidative damage in the testes, which was associated with testicular damage and decreased sperm counts (Jana et al 2010, Mosbah et al 2015. Interestingly, the testicular pathology caused by nicotine exposure in the adult animals (e.g., degeneration of seminiferous tubules, germ cell exfoliation, loss of Leydig cells, and disrupted spermatogenesis) (Jana et al 2010, Mosbah et al 2015 are remarkably similar to the histological results in the testes of male offspring who were exposed to nicotine in utero (Lagunov et al 2011, Paccola et al 2014, suggesting a common underlying mechanism.…”

“…Indeed, adult animals exposed to nicotine exhibited increased ROS production and oxidative damage in the testes, which was associated with testicular damage and decreased sperm counts (Jana et al 2010, Mosbah et al 2015. Interestingly, the testicular pathology caused by nicotine exposure in the adult animals (e.g., degeneration of seminiferous tubules, germ cell exfoliation, loss of Leydig cells, and disrupted spermatogenesis) (Jana et al 2010, Mosbah et al 2015 are remarkably similar to the histological results in the testes of male offspring who were exposed to nicotine in utero (Lagunov et al 2011, Paccola et al 2014, suggesting a common underlying mechanism. The relationship between nicotine, oxidative stress, and ovarian physiology has been less well studied, although nicotine has been shown to cause oxidative stress in Chinese Hamster Ovary cells (Yildiz et al 1998, Yildiz 2004.…”

Long-term treatment of hydrogen-rich saline abates testicular oxidative stress induced by nicotine in mice

“…Ultrastructural analysis revealed that in nicotine-treated rats, germ cells and junctional specialization between Sertoli cells were degenerated; collagen fibres under the irregular basal lamina increased; acrosomes were irregular and abnormally configured [5]. Cigarette smoke is a complex mixture of over 3,000 chemicals [6], among which nicotine is regarded as a major agent mediating the detrimental effects of smoking on male fertility [7][8][9]. Nicotine exposure reduces the weight of the testis, the number of spermatocytes and spermatids, and the testosterone levels, probably through its influence on pituitary gonadotropins and testicular antioxidant status, as nicotine is a central nervous system (CNS) depressor that can inhibit the neural stimulus essential for the release of pituitary gonadotropins.…”

“…Nicotine exposure reduces the weight of the testis, the number of spermatocytes and spermatids, and the testosterone levels, probably through its influence on pituitary gonadotropins and testicular antioxidant status, as nicotine is a central nervous system (CNS) depressor that can inhibit the neural stimulus essential for the release of pituitary gonadotropins. Besides, nicotine also contributes to reactive oxygen species (ROS) generation in testis [9][10][11]. Therefore, those 2 aspects can be regarded as 2 targets for treatment of male reproductive damages induced by nicotine.…”