Sensitive and vulnerable risks groups in relation to chemical risk assessment and management
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1 International Research and Research Training Centre Sensitive and vulnerable risks groups in relation to chemical risk assessment and management Niels E. Skakkebaek Department of Growth and Reproduction International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, EDMaRC, Rigshospitalet, University of Copenhagen, Denmark
2 Who are the most sensitive groups? The coming generations - in several ways
3 Increasing political focus on low fertility 50% fewer children and young people!
4 Possible Reasons for Declining Fertility Rates Use of contraception and widespread infertility
5 Increasing need for assisted reproduction Most recent data (2015) from Danish Fertility Society shows that: 8-10 % of the 2015 national birth cohort conceived after assisted reproduction (IVF,ICSI,IUI-H or IUI-D) In addition, almost 1% of children adopted
6 Possible Reasons for Declining Fertility Rates Use of contraception widespread infertility Women are too old when they start trying to become pregnant
7 Mean ages of Danish women delivering from
8 Mean ages of Danish women delivering from by American Physiological Society Blomberg Jensen et al, PLoS One, 2015; Skakkebaek et al. Physiol Rev 2016;96:55-97
9 Role of Male Factors For Fertility Adverse trends
10 Testicular cancer as a canary in the coal mine
11 Testicular cancer
12 Testicular cancer
13 Testicular cancer
14 Testicular cancer
15 Testicular cancer
16 Testicular cancer
17 Testicular cancer
18 Testicular cancer
19 Testicular cancer
20 Testicular cancer
21 Links and Trends in Male Reproductive Disorders - A Square Reduced fertility and childlessness Testicular cancer Lower Testosteron levels Birth defects of genitalia
22 Testicular Dysgenesis Syndrome Mother Environmental factors eg. Endocrine disrupting chemicals Son TESTICULAR DYSGENESIS DISTURBED SERTOLI CELL FUNCTION DECREASED LEYDIG CELL FUNCTION IMPAIRED GERM CELL DIFFERENTIATION ANDROGEN INSUFFICIENCY Reduced semen quality Testicular cancer Low Testostrone Genetic defects Abnormal penis (Hypospadias) Testis not in scrotum
23
24 Distinct Chemical Signatures of Danish and Finnish Breast Milk: Danes more Polluted Analyses of two dioxins Int J Androl DK FIN
25 1,2,3,6,7,8-HxCDD (pg/g l.w.) Validation of national chemical signatures of pollution Country 20 DK FIN FR ,2,3,4,7,8-HxCDD (pg/g l.w.) J.P. Antignac et al, Country-specific chemical signatures of persistent organic pollutants (POPs) in breast milk of French, Danish and Finnish women Environmental Pollution, Volume 218, 2016,
26 Problem: Sources of exposures often hidden Children had substantial amounts of UV filtres (used in sunscreens) in urine during a winter period without sun
27 Does regulation of chemicals help? Absolutely!
28 Exposure levels are not constant Temporal trends of DDE (ng/g fat) from Japan and Sweden Courtesy: Åke Bergman, Stockholm
29 Exposure levels are not constant Hexabromocyclododecane (HBCD, Flame Retardant) Courtesy : Åke Bergman, Stockholm
30 Are we sure that Endocrine Disrupting Chemicals (EDCs) play a role for male reproductive health? 1) Proof of principle The pesticide DBCP made men sterile 2) Animal studies convincingly show that exposure to pregnant animals can cause TDS-like symptoms in sons 3) Numerous human association studies show hormone disrupting effects of EDC in humans 4) Also direct effects in adult men More reading in: Skakkebaek et al. Physiological Reviews 2016
31
32 Conclusions Environment plays an important role for male reproductive health, which is particularly vulnerable during development Semen quality of young men now rarely meets all criteria of the WHO standard and widespread male infertility contributes to low birth rates and decreasing polulations (in spite of assisted reproduction) Good news: Adverse exposures can be reduced by 1. new knowledge by research on effects in humans 2. biomonitoring and 3. regulation of chemicals
33 International Research and Research Training Centre Niels E. Skakkebaek Department of Growth and Reproduction International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, EDMaRC, Rigshospitalet, University of Copenhagen, Denmark,
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