TY - JOUR

T1 - Response to "Comment on 'Maternal Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Male Reproductive Function in Young Adulthood

T2 - Combined Exposure to Seven PFAS'"

AU - Hærvig, Katia Keglberg

AU - Petersen, Kajsa Ugelvig

AU - Hougaard, Karin Sørig

AU - Lindh, Christian

AU - Ramlau-Hansen, Cecilia Høst

AU - Toft, Gunnar

AU - Giwercman, Aleksander

AU - Høyer, Birgit Bjerre

AU - Flachs, Esben Meulengracht

AU - Bonde, Jens Peter

AU - Tøttenborg, Sandra Søgaard

PY - 2023

Y1 - 2023

N2 - In his letter to the editor regarding our paper,1 Abraham raises an important discussion about co-exposure to per- and polyfluoroalkyl substances (PFAS) and other persistent organic pollutants, in particular dioxins.2 In our paper we acknowledged that “there might be factors, such as other chemicals or lifestyle, that might be associated with PFAS exposure which also have an impact on reproductive function.”1 Dioxins potentially constitute such co-exposure, and, if associated with semen quality, the observed inverse associations between PFAS and semen quality could be at least partly due to dioxins.As we did not assess dioxin levels in our sample, we relied on other studies to elucidate the extend of covariation. Abraham states that he found dioxins significantly correlated with PFAS in blood sampled from 74 mothers 11 months after giving birth in the late 1990s.2 We have not identified other studies reporting correlations between PFAS and dioxins, but correlations between perfluorooctane sulfonic acid (PFOS) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153)—a chemical with kinetic properties similar to dioxins, for example, long half-life and accumulation in adipose tissue—were 0.62 in blood of 1,250 Greenlandic, Polish, and Ukrainian pregnant females sampled in 2002–2004.3 Stratification by country generally revealed that correlations were strongest for the Greenlandic sample: 0.52 for PFOS and polychlorinated biphenyl (PCB)-153 vs. 0.20 for Poland and 0.23 for Ukraine.3 Because PFAS bind mainly to proteins, whereas PCBs are lipid-soluble, a high correlation is not expected. We would expect correlations of PFAS and dioxins in the Fetal Programming of Semen Quality cohort (which provided the data used in our study) similar to the PFOS–PCB-153 correlation observed in Ukraine and Poland.Based on these small-to-moderate correlations, we have little reason to believe that PFAS and dioxins would be highly correlated in our sample. Although we acknowledge the potency of dioxins, the lack of an established association between prenatal dioxin exposure and adult semen quality lessens our concern that our findings could originate from dioxin exposure. In the one study on this topic we were able to identify, Mocarelli et al. compared sperm concentration in sons of women who were exposed to either high levels of dioxins following the 1976 Seveso accident or background dioxin levels.4 Overall, sperm concentration was lower in the 39 sons born to highly exposed mothers, compared with the 58 sons born to less-exposed mothers. However, after stratification on breastfeeding, sperm concentration was lower only in breastfed sons of highly exposed mothers, not in formula-fed sons. This suggests that early postnatal exposure through breastfeeding rather than prenatal exposure drove the association. Furthermore, another study by our group indicated that prenatal exposure to organochlorine compounds, including a subgroup analysis of dioxin-like PCBs, was not associated with semen quality in a cohort of 178 males.5We urge other investigators to present data on correlations between PFAS and dioxins. We are currently conducting analyses on several groups of persistent and nonpersistent chemicals hoping to further advance our knowledge about health and reproductive effects of multipollutant exposures during fetal life.

AB - In his letter to the editor regarding our paper,1 Abraham raises an important discussion about co-exposure to per- and polyfluoroalkyl substances (PFAS) and other persistent organic pollutants, in particular dioxins.2 In our paper we acknowledged that “there might be factors, such as other chemicals or lifestyle, that might be associated with PFAS exposure which also have an impact on reproductive function.”1 Dioxins potentially constitute such co-exposure, and, if associated with semen quality, the observed inverse associations between PFAS and semen quality could be at least partly due to dioxins.As we did not assess dioxin levels in our sample, we relied on other studies to elucidate the extend of covariation. Abraham states that he found dioxins significantly correlated with PFAS in blood sampled from 74 mothers 11 months after giving birth in the late 1990s.2 We have not identified other studies reporting correlations between PFAS and dioxins, but correlations between perfluorooctane sulfonic acid (PFOS) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153)—a chemical with kinetic properties similar to dioxins, for example, long half-life and accumulation in adipose tissue—were 0.62 in blood of 1,250 Greenlandic, Polish, and Ukrainian pregnant females sampled in 2002–2004.3 Stratification by country generally revealed that correlations were strongest for the Greenlandic sample: 0.52 for PFOS and polychlorinated biphenyl (PCB)-153 vs. 0.20 for Poland and 0.23 for Ukraine.3 Because PFAS bind mainly to proteins, whereas PCBs are lipid-soluble, a high correlation is not expected. We would expect correlations of PFAS and dioxins in the Fetal Programming of Semen Quality cohort (which provided the data used in our study) similar to the PFOS–PCB-153 correlation observed in Ukraine and Poland.Based on these small-to-moderate correlations, we have little reason to believe that PFAS and dioxins would be highly correlated in our sample. Although we acknowledge the potency of dioxins, the lack of an established association between prenatal dioxin exposure and adult semen quality lessens our concern that our findings could originate from dioxin exposure. In the one study on this topic we were able to identify, Mocarelli et al. compared sperm concentration in sons of women who were exposed to either high levels of dioxins following the 1976 Seveso accident or background dioxin levels.4 Overall, sperm concentration was lower in the 39 sons born to highly exposed mothers, compared with the 58 sons born to less-exposed mothers. However, after stratification on breastfeeding, sperm concentration was lower only in breastfed sons of highly exposed mothers, not in formula-fed sons. This suggests that early postnatal exposure through breastfeeding rather than prenatal exposure drove the association. Furthermore, another study by our group indicated that prenatal exposure to organochlorine compounds, including a subgroup analysis of dioxin-like PCBs, was not associated with semen quality in a cohort of 178 males.5We urge other investigators to present data on correlations between PFAS and dioxins. We are currently conducting analyses on several groups of persistent and nonpersistent chemicals hoping to further advance our knowledge about health and reproductive effects of multipollutant exposures during fetal life.

KW - Female

KW - Male

KW - Humans

KW - Young Adult

KW - Adult

KW - Maternal Exposure

KW - Environmental Exposure

KW - Environmental Pollutants/toxicity

KW - Fluorocarbons/toxicity

U2 - 10.1289/EHP12600

DO - 10.1289/EHP12600

M3 - Letter

C2 - 36719214

VL - 131

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 1

M1 - 18004

ER -