Background Due to unique water and oil resistant properties used as: - Stain protection - In textiles - On metal surfaces - Food packaging paper

Transcription

1 Perfluoroalkyl substances and human reproductive health Gunnar Toft Aarhus University Department of Clinical Medicine Occupational Medicine

2 Background Due to unique water and oil resistant properties used as: - Stain protection - In textiles - On metal surfaces - Food packaging paper

3 Reproductive toxicity No adverse effect of PFOA on rat semen quality or reproductive organs (York et al 2010) Adult mice exposed to PFOS 21 days Wan et al 2011

4 Human exposure level Workers at PFAS producing facilities: - PFOS ~ 1500 ng/ml - PFOA ~ 5000 ng/ml General population: - PFOS ~ 35 ng/ml - PFOA ~ 5 ng/ml (Lau et al 2004)

5 Male reproductive hormones Reproductive hormones not affected among male PFOA production workers (Olsen et al 1998) LH positively associated to PFOA (Raymer et al 2011) (Not corroborated in other studies) Testosterone negatively associated to PFOA (Joensen et al 2013) similar trend in 2 out of 3 other studies

6 Semen quality Joenson et al 2009

7 Study population Pregnant women and spouses recruited in PFAS measured in serum in 2010 from 592 male and 1441 females. Greenland Kharkiv, Ukraine Warsaw, Poland

8 PFOS Greenland Poland Ukraine Greenland (n=196) Poland (n=190) Ukraine (n=203) Mean (SD) ng/ml 51.9 (24.4) 18.6 (5.67) 8.08 (3.98) Median (min, max) 44.7 (12.3, 161) 18.5 (8.20, 40.2) 7.60 (2.77, 29.9) Numbers below LOD 0 0 0

9 PFOA Greenland Poland Ukraine GR (n=196) PL (n=190) UA (n=203) Mean (SD) ng/ml 4.83 (1.60) 5.25 (2.14) 1.79 (2.75) Median (min, max) 4.54 (1.52, 13.7) 4.84 (1.48, 16.0) 1.29 (0.13, 35.0) Numbers below LOD

10 Determinants for PFOS exposure Determinants ß 95% CI R 2 Greenland PFOS 0.19 Seafood (days/week) 2.0 (0.46, 3.6) Age (year) 0.86 (0.37, 1.3) The (cups/day) 2.1 (0.31, 3.9) Area of living (Nuuk = reference) - West 2.3 (0.62, 3.8) East/Nord 2.3 (0.62, 3.8) Lindh et al 2012

11 % change sperm (Million/ml) % change in sperm motility (A+B) % change in normal sperm PFOS and semen quality Sperm count Motility Morphology nd tertile 3rd tertile nd tertile 3rd tertile * * 2nd tertile 3rd tertile PFOS PFOS PFOS Adjusted for adjusted for age, abstinence time, spillage, smoking; urogenital infections BMI and country. Toft et al 2012

12 PFOS and sperm morphologi Blue = Ukraine, Red = Poland, Green = Greenland

13 % change sperm (millon/ml) % change in sperm motility (A+B) % change in normal sperm PFOA and semen quality Sperm count Motility Morphology nd tertile 3rd tertile nd tertile * 3rd tertile nd tertile 3rd tertile PFOA PFOA PFOA Adjusted for adjusted for age, abstinence time, spillage, smoking; urogenital infections BMI and country

14 PFOA and sperm motility Blue = Ukraine, Red = Poland, Green = Greenland

15 PFAS and Time to Pregnancy 2 out of 4 previous studies indicates adverse effects of PFOS and PFOA on risk of infertility (Fei et al. 2009; Vestergaard et al. 2012; Whitworth et al. 2012; Buck Louis et al. 2013). Effect attenuated when restricted to primiparous women Longer TTP longer time to reaccumulate PFAS

16 Menstrual cycle P(trend) = Low Middle High PFOA exposure Lyngsø et al 2014

17 Prenatal exposure In utero exposure to PFOA and PFOS may affects the development of reproductive organs and adult reproductive function PFOA Reduced semen/oocyte quality Reduced testicular/ovary size Altered hormone profile

18 Recruitment Blood samples stored in Biobank 30 th pregnancy week Clinical examination (n= 176 sons daughters) Blood samples from mothers pregnancy week 30 assessed for levels of PFOA and PFOS Questionnaire, interview, and blood sample Letter to offspring about self-administered questionnaire (n=902)

19 % change of sperm concentration % change of total sperm count Semen quality P trend= P trend= low medium high low medium high Tertiles of PFOA Tertiles of PFOA Vested et al 2013

20 % change of LH % change of FSH Reproductive hormones P trend = P trend = low medium high low medium high Tertiles of PFOA Tertiles of PFOA

21 Difference in age (months) compared to low exposure Female reproductive function Age at menarche low medium high PFOA No association with menstrual cycle length reproductive hormones follicle number Kristensen et al 2013

22 Conclusion Adult exposure to PFAS may be associated to lower proportion of sperm with normal morphology, and testosterone production, but not associated to other measures of semen quality In utero exposure to FPAS may be related to long term effects on semen quality, FSH and LH Time to pregnancy and menstrual cycles may be affected in populations with high PFAS exposure In utero PFAS exposure appears to have only minor if any effects on female adult reproductive function, but may delay age of menarche