| Mobile phones have become an indispensable devices of daily life. Besides the traditional tele-communication function, smart phone has already become a convenient computer with the development of modern technology. Therefore, mobile phone is used more and more frequently, and people are more and more dependent on it. Currently, the widely used mobile phone siganl is 900MHz/1800MHz GSM/CDMA radiofrequency signal. The rapid growth of mobile phone use has been accompanied by a parallel increase in the density of electromagnetic field (EMF). Public concerns have been raised regarding the potentially harmful effects of radiofrequency electromagnetic radiation (RF-EMR) which is emitted from mobile phones and the towers. Many research indicated that RF-EMR may have harmful effects on nervous system and endocrine system, and may lead to fatigue, headache, and difficulty in concentration et al. Although the impact of mobile phone radiation on health is still controversial, the International Agency for Research on Cancer (IARC) still defines RF-EMR as "possibly carcinogenic to humans" (Group 2B).In addition to concern on the association between mobile phone use and cancer, the effects of mobile phone use on the male reproductive system have also attracted public attention, particularly when considering that mobile phones are often kept in trousers pockets and therefore close to testes for a long time. There is still no clear consensus of opinion on the effect of mobile phone on semen quality.In recent years, many research reported that male semen quality is declining. Our previous study on healthy men in the Chongqing area of southwest China also had indicated that semen quality was declining. The results of our investigation found that 61.1% of healthy men had at least one sperm parameter below normal threshold values compared with the World Health Organization (WHO) criteria. Semen quality is influenced by environmental factors, life style and genetic factors. Besides air and water pollution, EMR is also attacting public attention on the potential effect on semen quality.Currently, many labs performed investigation on the effect of mobile phone on semen quality. However, due to the variation of exposure system, measurement of semen and experimental design, there is still no conclusion on this question. This project investigated this topic on four aspects:systemic review, cohort study, cellular research and genetic research. This project provided clear data and reliable evidence on this public health problem, and benefit for the future research on this topic.The main results and conclusion is as follows:Part1:Association between mobile phone use and semen quality:A systemic review and meta-analysisWe prepared this systemic review and meta-analysis following standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. We searched the studies mainly from five international and Chinese literature databases published up to May 2013:two Chinese database:CNKI, the VIP databases and three international databases:Medline/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library. In the systemic review, we included eighteen studies with 3947 men and 186 rats, of which 12 studies (each 4 studies in human studies, in vitro studies and animal studies) with 1533 men and 97 rats were included in the meta-analyses. The results of systemic review indicated that most of the human epidemiological and in vitro laboratory studies suggested mobile phone use or radiofrequency exposure had harmful effects on semen parameters. However, the results of meta-analysis showed that mobile phone use did not have negative effects on semen parameters in human researches. For the in vitro studies, meta-analysis showed that radiofrequency radiation was harmful for sperm motility and viability in vitro (sperm motility pooled mean difference (MDs) (95%CI):-4.11 (-8.08,-0.13), viability -3.82 (-7.00,-0.65)). As for animal studies, radiofrequency exposure had adverse effects on sperm concentration and motility (for sperm concentration:pooled MDs (95%CI):-8.75 (-17.37,-0.12), for sperm motility:-17.72 (-32.79,-2.65)). Data from current studies indicate that mobile phone use had potential harmful effects on semen parameters. A further multi-centered and standardized study is essential to evaluate the potential risk of mobile phone use on semen quality.Part2:Effects of cell phone use on semen parameters:results from the MARHCS cohort study in Chongqing, ChinaThe mobile phone use information of 794 young men was selected and documented from the Male Reproductive Health in Chongqing College students (MARHCS) cohort study in 2013,666 in 2014 and 568 in 2015, respectively. In the univariate regression analyses, the results indicated that the daily duration of talking on mobile phone was significantly correlated with the decrease of semen parameters, including sperm concentration [β coefficient=-6.32% per unit daily duration of talking on the mobile phone (h); 95% confidence interval (CI),-11.94,-0.34] and total sperm count (-8.23; 95% CI,-14.38,-1.63) in 2013; semen volume (-8.37; 95% CI,-15.93,-0.13) and total sperm count (-16.59; 95% CI,-29.91,-0.73) in 2015]. Mobile phone internet use via cellular networks was correlated with the decrease of sperm concentration and total sperm counts in 2013 and the decrease of semen volume in 2015 as well. We used Multivariate analyses to adjust the effects of potential confounding factors, and the associations between internet use and semen parameters remained significantly negative. The correlation between talking on the mobile phone and semen parameters remained consistent but no longer significantly negative throughout the three years, and the negative association was observed statistically significant in a mixed model that considered all three years data on talking on the cell phone and semen quality. These results indicated that a couple of aspects of mobile phone use may negatively influence semen quality in men by declining semen volume, sperm concentration, or sperm count, thereby impairing male fertility.Part3:The protective effect of autophagy on mouse spermatocyte derived cells exposure to 1800MHz radiofrequency electromagnetic radiationTo investigate whether RF-EMR exposure is capable to induce autophagy in the spermatocyte, GC-2 cells (mouse spermatocyte-derived cells) were exposed to 1800 MHz GSM (Global System for Mobile Communication) signals in GSM-Talk mode at SAR (specific absorption rate) values of lw/kg,2w/kg or 4w/kg for 24h, respectively. These results showed that the expression of LC3-Ⅱ increased in a time-and dose-dependent manner with RF exposure, and indicated a significant change at the SAR value of 4w/kg. GFP-LC3 transient transfection assay and transmission electron microscopy (TEM) analysis further confirmed the autophagosome formation and the occurrence of autophagy. Furthermore, the conversion of LC3-Ⅰ to LC3-Ⅱ was enhanced by co-culture with Chloroqrine (CQ), suggesting that autophagic flux could be enhanced under RF exposure. Intracellular ROS levels increased significantly in a time-and dose-dependent manner after RF exposure. Pretreatment with anti-oxidative reagent NAC significantly declined the conversion of LC3-Ⅰ to LC3-Ⅱ and abolished the degradation of p62 induced by RF exposure. Besides, RF exposure significantly increased the phosphorylation of extracellular-signal-regulated kinase (ERK) at the SAR value of 2w/kg and 4w/kg. Moreover, we found that RF exposure did not alter the percentage of apoptotic cells, but inhibition of autophagy is capable to increase the apoptotic cells. These data suggested that 1800MHz GSM exposure (4w/kg) could enhance autophagy flux, and ROS generation is involved in this process. Taken together, autophagy plays a vital role in preventing cells from apoptotic cell death after RF exposure.Part4:High throughput gene chip analysis on the effect of mobile phone radiation on DNA damage repair signaling pathwayDNA damage may lead to cell death, cacinogenesis et al. There is still no consistent conclusion on the effect of long time mobile phone radiation exposure on DNA damage. This session adopted high throughput quantitive PCR to detect the change of mRNA level of 84 DNA damage repair related genes in GC-2 cells after 24h 1800MHz RF-EMR (4w/kg) exposure. The results indicated that only 2 genes down-regulated and 1 gene upregulated after RF exposure. Other genes did not alter. From these preliminary data, RF radiation is not sufficient to activate DNA damge and repair signaling pathway.Taken together, this project deeply and systemicly investigated the correlation between mobile phone radiation and semen quality in multiple view and aspect:systemic review and Meta analysis; epidemical cohort study; cell biological and molecular research. Long time mobile phone radiation exposure has potential risk on semen quality. Under the experimental exposure condition, RF-EMR is not sufficient to induce apoptosis and DNA damage. Meanwhile, autophagy plays a vital role in preventing cells from apoptotic cell death after RF exposure. This project provided original data on the research on mobile phone radiation and semen quality, which benefits for the future research. |
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