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Environmental xenobiotics and male reproductive health

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Asian Journal of Andrology 2014年第1期16卷 3-4页

作者： jens peter bonde Aleksander Giwercman Department of Occupational and Environmental Medicine Frederiksberg and Bispebjerg Hospital University of Copenhagen Denmark Reproductive Medicine Centre Skne University Hospital Maim6 Sweden.

Lessons from the occupational arena fdemonstrate the potential of industrial 4chemicals to damage human testicular function. An important but still unresolved question is whether low-level xenobiotic exposure of the general population poses a hazard. In this volume of the Asian Journal of Andrology, this issue is addressed by a series of reviews on xenobiotic exposure profiles, possible biological mechanisms, research methods and knowledge on impact of specific exposures. Interdisciplinary research fields as gene-environment interaction and male-mediated developmental toxicity is also addressed. Papers are cross-linked by answers to questions mutually put forward by the authors.

关键词： xenobiotics chemicals occupational

Persistent organic pollutants and male reproductive health

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Asian Journal of Andrology 2014年第1期16卷 71-80页

作者： Anne Vested Aleksander Giwercman jens peter bonde Gunnar Toil- Department of Occupational Medicine Danish Ramazzini Centre Aarhus University Hospital Aarhus Denmark Reproductive Medicine Centre Lund University Skane University Hospital Malm6 Sweden Department of Occupational and Environmental Medicine Bispebjerg Hospital of Copenhagen University

Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.

关键词： endocrine disruption male reproduction persistent organic compounds reproductive hormones semen quality

On environmental threats to male infertility

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Asian Journal of Andrology 2013年第2期15卷 199-200,I0005页

作者： Allen J Wilcox jens peter E bonde Epidemiology Branch National Institute of Environmental Health Sciences Durham NC 27709-2233 USA Department of Occupational and Environmental Medicine University Hospital of Copenhagen Copenhagen NV DK-2400 Denmark

The possibility that environmental pollutants damage human fertility is a topic of both public concern and scientific interest. The effect of environmental factors on male fertility （semen parameters） has been a special focus, stimulated in part by the dramatic damage inflicted by the pcstlcide DBCP on testicular function. Extensive searches for testicular toxicants （in particular, the proposed effects of endocrine-disrupting compounds through fetal exposure） have produced little hard evidence of impairment in humans. This scarcity of evidence may reflect the difficultles of studying human fertility. Future fertifity studies should consider the wide spectrum of environmental exposures that plausibly affect reproduction.

关键词： TESTICULAR DYSGENESIS SYNDROME IN-UTERO EXPOSURE SPERM COUNTS SEMEN QUALITY ENDOCRINE DISRUPTION REPRODUCTIVE-TRACT FERTILITY PREGNANCY PHTHALATE SMOKING

Misconceptions about falling sperm counts and fertility in Europe

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Asian Journal of Andrology 2013年第2期15卷 195-198,I0005页

作者： Egbert R te Velde jens peter bonde Department of Public Health Erasmus University MC Rotterdam GE 3015 The Netherlands Reproductive Medicine Utrecht University Utrecht CM 3584 The Netherlands Department of Occupational and Environmental Medicine Bispebjerg Hospital University of Copenhagen Copenhagen NV 24C0 Denmark

The Science Policy Briefing on male reproductive health pubfished by the authoritative European Science Foundation （ESF） in 2010 echoes the views expressed in the famous paper by *** et al, suggesting that mean sperm counts decreased by 50%. The authors are convinced that the male reproductive system in industrialized countries is under attack from envi- ronmental chemicals. This may have farreaching consequences for the reproductive capacity of future generations. Their arguments, however, contain some misconceptions about declining sperm quality and fertifity. Although there is reason for concern about the effect of environmental pollution, the authors＇ pessimism is not justified.

关键词： TIME TRENDS INFERTILITY TREATMENT REGIONAL DIFFERENCES WAITING TIME PREGNANCY SEMEN EPIDEMIOLOGY POPULATION PREVALENCE FECUNDITY

Neurobiological mechanisms underlying delayed expression of posttraumatic stress disorder:A scoping review

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World Journal of Psychiatry 2022年第1期12卷 151-168页

作者： Geert E Smid Jonna Lind jens peter bonde ARQ Centrum'45 ARQ National Psychotrauma CentreDiemen 1112XENetherlands Department of Humanist Chaplaincy Studies University of Humanistic StudiesUtrecht 3512 HDNetherlands ARQ Centre of Excellence on War Persecution and ViolenceARQ National Psychotrauma CentreDiemen 1112XENetherlands Department of Occupational and Environmental Medicine Frederiksberg and Bispebjerg HospitalCopenhagen 2400Denmark Department of Public Health University of CopenhagenCopenhagen 1014Denmark

BACKGROUND The capacity of posttraumatic stress disorder(PTSD)to occur with delayed onset has been documented in several systematic reviews and *** models of PTSD may provide insight into the mechanisms underlying the progressive increase in PTSD symptoms over time as well as into occasional occurrences of long-delayed PTSD with few prodromal *** To obtain an overview of key concepts explaining and types of evidence supporting neurobiological underpinnings of delayed *** A scoping review of studies reporting neurobiological findings relevant to delayed PTSD was performed,which included 38 studies in the qualitative *** Neurobiological mechanisms underlying PTSD symptoms,onset,and course involve several interconnected *** mechanisms involve the neurocircuitry of fear,comprising several structures,such as the hippocampus,amygdala,and prefrontal cortex,that are amenable to time-dependent increases in activity through sensitization and *** network models explain generalization of the fear *** mechanisms consist of autonomic nervous system and hypothalamic-pituitary-adrenocortical axis responses,both of which may be involved in sensitization to *** mechanisms are characterized by immune activation,which is sometimes due to the effects of traumatic brain ***,neurobehavioral/contextual mechanisms involve the effects of intervening stressors and mental and physical disorder comorbidities,and these may be particularly relevant in cases of long-delayed *** Thus,delayed PTSD may result from multiple underlying neurobiological mechanisms that may influence the likelihood of developing prodromal symptoms preceding the onset of full-blown PTSD.

关键词： Posttraumatic stress disorder Delayed expression Sensitization Neurobiology Neuroendocrine Neuroinflammatory

Gene-environment interaction and male reproductive function

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Asian Journal of Andrology 2010年第3期12卷 298-307,I0007页

作者： Jonatan Axelsson jens peter bonde Yvonne L. Giwercman Lars Rylander Aleksander Giwercman Reproductive Medicine Centre Skane University Hospital Malmo 20502 Sweden Division of Occupational and Environmental Medicine Lund University Lund 22185 Sweden Department of Occupational Medicine Copenhagen University Bispebjerg Hospital Copenhagen NV2400 Denmark Department of Clinical Sctences Malmo Lund University Malmo 20502 Sweden

As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring.

关键词： endocrine disruption gene-environment interaction persistent organic pollutants semen quality testicular cancer

Male reproductive organs are at risk from environmental hazards

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Asian Journal of Andrology 2010年第2期12卷 152-156页

作者： jens peter bonde Department of Occupational and Environmental Medicine Bispebjerg University HospitalDK-2400 Copenhagen NVDenmark

Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction,infertility,cryptorchidism,hypospadias and testicular cancer. Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However,the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation,radiant heat and a number of known toxicants. So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures （radiant heat,ionizing radiation,high frequency electromagnetic radiation）,chemical exposures （some solvents as carbon disulfide and ethylene glycol ethers,some pesticides as dibromochloropropane,ethylendibromide and DDT/DDE,some heavy metals as inorganic lead and mercury） and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures,but millions of workers in less affluent countries are at risk from reproductive *** data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world. For other toxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates,bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones. Finally,there are data indicating a particular vulnerability of the fetal testis to toxicants-for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.

关键词： epidemiology fertility occupation risk factors semen quality

Environmental mercury exposure, semen quality and reproductive hormones in Greenlandic Inuit and European men： a cross-sectional study

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Asian Journal of Andrology 2013年第1期15卷 97-104页

作者： Emina Mocevic Ina O Specht Jacob L Marott Aleksander Giwercman Bo AG Jonsson Gunnar Toft Thomas Lundh jens peter bonde Department of Occupational and Environmental Medicine Copenhagen University Hospital Bispebjerg Copenhagen NV DK-2400 Denmark Reproductive Medicine Centre Sk~ne University Hospital Malm6 Lund University Malm6 SE-20502 Sweden Division of Occupational and Environmental Medicine Department of Laboratory Medicine Lund University Lund SE-22185 Sweden Department of Occupational Medicine Aarhus University Hospital Aarhus DK-8000 Denmark

Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml-1 in Greenland （0.2- 385.8 ng ml-1）, 1.0 ng m1-1 in Poland （0.2-6.4 ng ml-z） and 1.0 ng ml-I in Ukraine （0.2-4.9 ng ml-1）. We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland （p=0.074, 95% confidence interval （CI）=0.021 to 0.126） and in an analysis including men from all three regions （p=0.067, 95% C1=0.024 to O. 110）. The association may be due to beneficial effects of polyunsaturated fatty acids （PUFAs）, which are contained in seafood and fish. No significant association （P〉O.05） was found between blood concentrations of mercury and any of the other measured semen characteristics （semen volume, total sperm count, sperm concentration, morphology and motility） and reproductive hormones （free androgen index {FAI）, follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone and LH xtestosterone） in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng m1^-1 has adverse effects on biomarkers of male reproductive health.

关键词： blood mercury concentration environmental mercury exposure male fertility reproduction reproductive hormones semen characteristics semen quality

Relationship between apoptotic markers in semen from fertile men and demographic, hormonal and seminal characteristics

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Asian Journal of Andrology 2012年第6期14卷 890-896页

作者： Ina O Specht Marcello Spano Karin S Hougaard Gian C Manicardi Davide Bizzaro Gunnar Toft Aleksander Giwercman jens-peter E bonde Department of Occupational and Environmental Medicine University Hospital of Copenhagen Copenhagen NV DK-2400 Denmark Laboratory of Toxicology Unit of Radiation Biology and Human Health ENEA Casaccia Research Center Rome 1-00123 Italy National Research Centre for the Working Environment Copenhagen 0 DK-2100 Denmark Dipartimento di Scienze Agrarie e degli Alimenti Universita di Modena e Reggio Emilia Reggio Emilia 1-42121 Italy Department of Life and Environmental Sciences Polytechnic University of Marche Ancona 1-60131 Italy epartment of Occupational Medicine Aarhus University Hospital Aarhus C DK-8000 Denmark Reproductive Medicine Centre Maim6 University Hospital Lund University MalmO SE-20502 Sweden

Apoptosis in the testis has two putative roles during normal spermatogenesis; limitation of the germ cell population to numbers that can be supported by the Sertoli cells, and, possibly, selective depletion of meiotic and postmeiotic abnormal germ cells. We investigated the demographic and biological correlates of the pro-apoptotic marker Fas and the anti-apoptotic marker Bcl-xL in sperm cells of fertile men. Six hundred and four men from Greenland, Poland and Ukraine were consecutively enrolled during their pregnant wife＇s antenatal visits. Semen analysis was performed as recommended by the World Health Organization. Immunofluorescence coupled to flow cytometry was utilized for detection of apoptotic markers in the sperm cell. DNA damage was assessed by flow cytometry using both the sperm chromatin structure assay （SCSA） and the terminal deoxynucleotidyl transferase dUTP nick end labelling （TUNEL） assay. The percentage of Fas-positive sperm cells was higher in men with high total sperm count （P〈O.01）, more motile sperms （P=-O.04） and fewer sperm head defects （P=-O.05）. These associations were consistent within and across study regions. Furthermore, testosterone, follicle-stimulating hormone （FSH） and sexual hormone-binding globulin （SHBG） were significantly negatively correlated with Fas within and across regions as well. The data indicated no association between the anti-apoptotic Bcl-xL marker and semen or personal characteristics. The finding of Fas-positive sperm cells associated with better semen quality in a cohort of spouses of pregnant women seems different from previous data obtained in infertile men and warrants further investigation to clarify the biological significance of sperm apoptotic markers.

关键词： apoptosis Bcl-x protein Fas-associated death domain protein fertility sperm chromatin structure assay (SCSA) sper- matozoa TUN EL assay