Male Reproductive Health Disorders and the Potential Role of Exposure to Environmental Chemicals

Male Reproductive Health Disorders and the Potential Role of Exposure to Environmental Chemicals Written by Professor Richard Sharpe Commissioned by CHEM Trust about the author Professor Richard M Sharpe MRC Human Reproductive Sciences Unit Centre for Reproductive Biology The Queen’s Medical Research Institute 47 Little France Crescent Edinburgh EH16 4TJ t: +44 (0) 131 242 6387 f: +44 (0) 131 242 6197 e: r.sharpe@hrsu.mrc.ac.uk about CHEM Trust Professor Richard Sharpe has worked in the area of male reproductive endocrinology for more than 30 years. He has expertise in all aspects of testicular development and function and has wide experience in the field of endocrine disruptors and the effects of environmental and lifestyle factors on male reproductive health. He is the author of more than 200 publications. CHEM Trust, founded in 2007, raises awareness of the role that exposure to chemicals may play in ill health. The charity works to improve chemicals legislation and to protect future generations of humans and wildlife. From a human health perspective, CHEM Trust’s mission is to ensure that future generations are healthy and can reach their full potential in terms of behaviour, intelligence and ability to have children. www.chemtrust.org.uk While this report was commissioned by CHEM Trust, the views expressed and the conclusions reached are those of the author, and are not necessarily those of CHEM Trust. Further copies of this report can be downloaded free from www.chemtrust.org.uk contact e: gwynne.lyons@chemtrust.org.uk Cover photos clockwise from top left, include: A fetus ultrasound scan at 14 weeks [Jon Schulte]; Fetus growing; Teenage male basketball team; Man kissing pregnant tummy [Vladimir Piskunov]; Baby holding father’s nose; Sperm and egg; Baby’s face; Father and son at sunset [Andrew Penner]; i all courtesy of [©iStockphoto.com] Male Reproductive Health Disorders and the Potential Role of Environmental Chemical Exposures contents List of abbreviations Summary Introduction Aims, perspectives and limitations of this review Overview of prevalence and trends in male reproductive health disorders • • • • Testicular dysgenesis syndrome (TDS) • • ............................................................................................................ 1 ............................................................................................................5 ............................................................................................................8 ........................................................................................................... 9 ......................................................................................................... 10 Low sperm counts/male infertility....................................................................... 10 Testicular germ cell tumours (TGCT) .................................................................. 12 Cryptorchidism ..................................................................................................... 13 Hypospadias ......................................................................................................... 15 .............................................................................................................. 16 Male programming window ................................................................................. 17 Overview of experimental animal studies involving environmental chemical (EC) induction of ‘TDS-like’ disorders.................................................. 19 o Anti-androgenic ECs and TDS .......................................................................19 o Oestrogenic ECs and TDS ............................................................................. 20 o Risk assessment of ECs and EC mixtures ..................................................... 22 Causes of TDS disorders in humans • • .............................................................................................................. 24 Genetic causes/predisposition ............................................................................. 24 Evidence that environmental factors, such as ECs, can cause TDS in humans .. 25 o EC exposure and cryptorchidism and/or hypospadias ................................ 26 • Quality assessment of the various studies and of the data obtained ................. 26 • Evaluation of published studies ........................................................................... 27 o EC exposure and hormone levels .................................................................. 30 • Human exposure to phthalates ............................................................ 31 • Phthalate effects in the human ............................................................. 32 • Do hormone levels at birth/neonatally reflect those in fetal life? ....... 35 o EC exposure and low sperm counts .............................................................. 36 • Fetal EC exposure and sperm counts in adulthood ............................. 36 • Adult EC exposure and sperm counts .................................................. 37 o EC exposure and testicular germ cell tumours (TGCT) ............................... 39 Conclusions and future perspectives References Table 1 .............................................................................................................. 41 .............................................................................................................. 43 Some of the inherent difficulties in establishing if human exposure to ECs is associated causally with TDS (testicular dysgenesis syndrome) disorders. ..... 25 ii Male Reproductive Health Disorders and the Potential Role of Environmental Chemical Exposures List of abbreviations AF amniotic fluid AGD anogenital distance.The distance between the anus and genitals, which is longer in men. AH aryl hydrocarbon AR androgen receptor BBzP butylbenzyl phthalate CG chorionic gonadotrophin or human chorionic gonadotrophin (hCG) CIS carcinoma in situ cells, cells which are precursor cells to cancer DBP di-n-butyl phthalate DDE 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene DDT 1,1-bis-(4-chlorophenyl)-2,2,2-trichloroethane DEHP di(2-ethylhexyl) phthalate DEP diethyl phthalate DES diethylstilboestrol ECs environmental chemicals ED endocrine disruptor HCB hexachlorobenzene HCE heptachloroepoxide -HCCH -hexachlorocyclohexane LH luteinising hormone MBP mono-n-butyl phthalate MBzP mono-benzyl phthalate MEHHP mono(2-ethyl-5-hydroxy-hexyl) phthalate MEHP mono(2-ethylhexyl) phthalate MEOHP mono(2-ethyl-5-oxo-hexyl) phthalate MMP mono-methyl phthalate PAHs polycyclic aromatic hydrocarbons PBDE polybrominated diphenyl ethers PCBs polychlorinated biphenyls PFOS perfluorooctane sulfonate- a pefluorinated chemical PFOA perfluorooctanic acid – a perfluorinated chemical POPs persistent organic pollutants TCDD 2,3,7,8-tetrachlorodebenzo-p-dioxin TDS testicular dysgenesis syndrome TGCT testicular germ cell tumours WHO World Health Organisation 1 Male Reproductive Health Disorders and the Potential Role of Environmental Chemical Exposures Diagram to illustrate potential TDS effects due to in-utero exposure Copyright the Lucina Foundation, all rights reserved. Diagram to illustrate cryptorchidism (undescended testes) Diagram to illustrate four types of hypospadias 2 ... - tailieumienphi.vn