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      In vitro assessment of reproductive toxicity of cigarette smoke and deleterious consequences of maternal exposure to its constituents

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          Abstract

          Cigarette smoke is known to be a serious health risk factor and considered reproductively toxic. In the current study, we investigated whether constituents of cigarette smoke, pyrazine, 2-ethylpyridine, and 3-ethylpyridine, adversely affect reproductive functioning such as oocyte maturation and sperm capacitation. Our findings indicated that three smoke components were involved in retardation of oocyte maturation in a dose-dependent manner and the lowest-observed-adverse-effect level (LOAEL) was determined to be 10-10M. However, individual smoke components administrated at the LOAEL did not attenuate oocyte maturation, demonstrating that all three toxicants were equally required for the observed growth impairment. When exposed to all three components at 10-10M during in vitro capacitation, murine sperm lost forward progression and were unable to show adequate hyperactivation, which is indicative of the incompletion of the capacitation process. Only sperm administrated with 3-ethylpyridine alone showed significant reduction in capacitation status, suggesting the chemical is the one responsible for disrupting sperm capacitation. Taken together, this is the first report that documents the effect of cigarette smoke components on oocyte maturation and sperm capacitation. The present findings demonstrate the adverse effects of smoke constituents of mammalian reproduction and the differences in sensitivity to smoke components between male and female gametes. Since both processes take place in the female reproductive system, our data provide new insights into deleterious consequences of maternal exposure to cigarette smoke.

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          Cadmium: toxic effects on the reproductive system and the embryo.

          The heavy metal cadmium (Cd) is a pollutant associated with several modern industrial processes. Cd is absorbed in significant quantities from cigarette smoke, and is known to have numerous undesirable effects on health in both experimental animals and humans, targeting the kidneys, liver and vascular systems in particular. However, a wide spectrum of deleterious effects on the reproductive tissues and the developing embryo has also been described. In the testis, changes due to disruption of the blood-testis barrier and oxidative stress have been noted, with onset of widespread necrosis at higher dosage exposures. Incorporation of Cd into the chromatin of the developing gamete has also been demonstrated. Ovarian Cd concentration increases with age, and has been associated with failure of progression of oocyte development from primary to secondary stage, and failure to ovulate. A further mechanism by which ovulation could be rendered ineffective is by failure of pick-up of the oocyte by the tubal cilia due to suboptimal expansion of the oocyte-cumulus complex and mis-expression of cell adhesion molecules. Retardation of trophoblastic outgrowth and development, placental necrosis and suppression of steroid biosynthesis, and altered handling of nutrient metals by the placenta all contribute to implantation delay and possible early pregnancy loss. Cd has been shown to accumulate in embryos from the four-cell stage onwards, and higher dosage exposure inhibits progression to the blastocyst stage, and can cause degeneration and decompaction in blastocysts following formation, with apoptosis and breakdown in cell adhesion. Following implantation, exposure of experimental animals to oral or parenteral Cd causes a wide range of abnormalities in the embryo, depending on the stage of exposure and dose given. Craniofacial, neurological, cardiovascular, gastrointestinal, genitourinary, and limb anomalies have all been described in placentates, with axial abnormalities and defects in somite structure noted in fish and ventral body wall defect and vertebral malformation occurring in the chick. In this paper, we examine the mechanisms by which Cd can affect reproductive health, and consider the use of micronutrients in prevention of these problems.
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            Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention.

            Much is now known about the carcinogens in cigarette smoke, their conversion to forms that react with DNA, and the miscoding properties of the resulting DNA adducts that cause the many genetic changes known to exist in human lung cancer. The chronic exposure of pulmonary DNA to a multitude of metabolically activated carcinogens is consistent with our current understanding of cancer as a disease resulting from many changes in key genes regulating growth. This review illustrates how this solid foundation of knowledge can be used to find new ways to prevent lung cancer. Three prevention-related topics are discussed: human uptake of tobacco carcinogens as a way of assessing risk and investigating mechanisms; individual differences in the metabolic activation and detoxification of carcinogens, which may relate to cancer susceptibility; and chemoprevention of lung cancer in smokers and ex-smokers. These new approaches are necessary as adjuncts to education and cessation efforts, which despite some success have not eliminated tobacco smoking.
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              Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study.

              To investigate levels of seminal oxidative stress (OS) and sperm quality in a group of infertile men with a history of cigarette smoking. A prospective clinical study. Male infertility clinic, Urological Institute, the Cleveland Clinic Foundation, Cleveland, Ohio. Infertile men who smoked cigarettes (n = 20), infertile men who were nonsmokers (n = 32), and healthy nonsmoking donors (n = 13). Genital examination, standard semen analysis, sperm DNA damage. Levels of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) measured by a chemiluminescence assay and seminal OS assessed by calculating a ROS-TAC score. Sperm DNA damage was measured by sperm chromatin structure assay. Smoking was associated with a 48% increase in seminal leukocyte concentrations (P<.0001), a 107% increase in ROS levels (P=.001), and a 10-point decrease in ROS-TAC scores (P=.003). Differences in standard sperm variables and DNA damage indices between the infertile smokers and infertile nonsmokers were not statistically significant. Infertile men who smoke cigarettes have higher levels of seminal OS than infertile nonsmokers. Given the potential adverse effects of seminal OS on fertility, physicians should advise infertile men who smoke cigarettes to quit.
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                Author and article information

                Journal
                bres
                Biological Research
                Biol. Res.
                Sociedad de Biología de Chile (Santiago, , Chile )
                0716-9760
                2012
                : 45
                : 2
                : 101-109
                Affiliations
                [02] Taipei orgnameChinese Culture University orgdiv1Graduate Institute of Biotechnology China
                [01] Taipei orgnameChinese Culture University orgdiv1Department of Life Science China
                Article
                S0716-97602012000200001 S0716-9760(12)04500201
                10.4067/S0716-97602012000200001
                23096353
                c6f811f2-1277-46a1-89a3-0c75ce309e24

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 21 September 2011
                : 09 January 2012
                : 12 March 2012
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 87, Pages: 9
                Product

                SciELO Chile

                Categories
                Research Articles

                sperm capacitation,reproductive toxicity,oocyte maturation,cigarette smoke

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