PMID- 37482334
OWN - NLM
STAT- MEDLINE
DCOM- 20230918
LR  - 20230918
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 335
DP  - 2023 Oct 15
TI  - PFAS association with kisspeptin and sex hormones in teenagers of the HBM4EU 
      aligned studies.
PG  - 122214
LID - S0269-7491(23)01216-2 [pii]
LID - 10.1016/j.envpol.2023.122214 [doi]
AB  - Exposure to Perfluoroalkyl acids (PFAS) can impair human reproductive function, 
      e.g., by delaying or advancing puberty, although their mechanisms of action are 
      not fully understood. We therefore set out to evaluate the relationship between 
      serum PFAS levels, both individually and as a mixture, on the 
      Hypothalamic-Pituitary-Gonadal (HPG) axis by analyzing serum levels of 
      reproductive hormones and also kisspeptin in European teenagers participating in 
      three of the HBM4EU Aligned Studies. For this purpose, PFAS compounds were 
      measured in 733 teenagers from Belgium (FLEHS IV study), Slovakia (PCB cohort 
      follow-up), and Spain (BEA study) by high performance liquid 
      chromatography-tandem mass spectrometry (HPLC/MS) in laboratories under the 
      HBM4EU quality assurance quality control (QA/QC) program. In the same serum 
      samples, kisspeptin 54 (kiss-54) protein, follicle-stimulating hormone (FSH), 
      total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) 
      levels were also measured using immunosorbent assays. Sex-stratified single 
      pollutant linear regression models for separate studies, mixed single pollutant 
      models accounting for random effects for pooled studies, and g-computation and 
      Bayesian kernel machine regression (BKMR) models for the mixture of the three 
      most available (PFNA, PFOA, and PFOS) were fit. PFAS associations with 
      reproductive markers differed according to sex. Each natural log-unit increase of 
      PFOA, PFNA, and PFOS were associated with higher TT [18.41 (6.18; 32.31), 15.60 
      (7.25; 24.61), 14.68 (6.18; 24.61), respectively] in girls, in the pooled 
      analysis (all studies together). In males, G-computation showed that PFAS mixture 
      was associated with lower FSH levels [-10.51 (-18.81;-1.36)]. The BKMR showed the 
      same patterns observed in G-computation, including a significant increase on male 
      Kiss-54 and SHBG levels. Overall, effect biomarkers may enhance the current 
      epidemiological knowledge regarding the adverse effect of PFAS in human HPG axis, 
      although further research is warranted.
CI  - Copyright (c) 2023. Published by Elsevier Ltd.
FAU - Rodriguez-Carrillo, Andrea
AU  - Rodriguez-Carrillo A
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium; Toxicological Centre, University of Antwerp, Universiteitsplein, 1, 
      2610, Wilrijk, Belgium.
FAU - Remy, Sylvie
AU  - Remy S
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium.
FAU - Koppen, Gudrun
AU  - Koppen G
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium.
FAU - Wauters, Natasha
AU  - Wauters N
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium.
FAU - Freire, Carmen
AU  - Freire C
AD  - Biomedical Research Center (CIBM), University of Granada, 18016 Granada, Spain; 
      Instituto de Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, 
      Spain; Consortium for Biomedical Research in Epidemiology and Public Health 
      (CIBERESP), Spain.
FAU - Olivas-Martinez, Alicia
AU  - Olivas-Martinez A
AD  - Biomedical Research Center (CIBM), University of Granada, 18016 Granada, Spain.
FAU - Schillemans, Tessa
AU  - Schillemans T
AD  - Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental 
      Medicine, Karolinska Institutet, Sweden.
FAU - Akesson, Agneta
AU  - Akesson A
AD  - Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 
      Spain.
FAU - Desalegn, Anteneh
AU  - Desalegn A
AD  - Division of Food Safety, Norwegian Institute of Public Health, Norway.
FAU - Iszatt, Nina
AU  - Iszatt N
AD  - Division of Climate and Environmental Health, Norwegian Institute of Public 
      Health, Norway.
FAU - den Hond, Elly
AU  - den Hond E
AD  - Provincial Institute for Hygiene, Antwerp, Belgium.
FAU - Verheyen, Veerle
AU  - Verheyen V
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium.
FAU - Fabelova, Lucia
AU  - Fabelova L
AD  - Department of Environmental Medicine, Faculty of Public Health, Slovak Medical 
      University, Bratislava, Slovakia.
FAU - Murinova, Lubica Palkovicova
AU  - Murinova LP
AD  - Department of Environmental Medicine, Faculty of Public Health, Slovak Medical 
      University, Bratislava, Slovakia.
FAU - Pedraza-Diaz, Susana
AU  - Pedraza-Diaz S
AD  - National Centre for Environmental Health, Instituto de Salud Carlos III, Madrid, 
      Spain.
FAU - Castano, Argelia
AU  - Castano A
AD  - National Centre for Environmental Health, Instituto de Salud Carlos III, Madrid, 
      Spain.
FAU - Garcia-Lario, Jose Vicente
AU  - Garcia-Lario JV
AD  - Hospital Universitario Clinico San Cecilio, Granada, Spain.
FAU - Cox, Bianca
AU  - Cox B
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium.
FAU - Govarts, Eva
AU  - Govarts E
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium.
FAU - Baken, Kirsten
AU  - Baken K
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium.
FAU - Tena-Sempere, Manuel
AU  - Tena-Sempere M
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Menendez Pidal s/n. 
      14004., Cordoba, Spain; Department of Cell Biology, Physiology and Immunology, 
      University of Cordoba, Campus de Rabanales, Ctra. Madrid-Cadiz, Km. 396. 14071. 
      Cordoba, Spain; University Hospital Reina Sofia, Menendez Pidal s/n. 14004, 
      Cordoba, Spain; CIBER Pathophysiology of Obesity and Nutrition, Carlos III Health 
      Institute, Menendez Pidal s/n. 14004. Cordoba, Spain.
FAU - Olea, Nicolas
AU  - Olea N
AD  - Biomedical Research Center (CIBM), University of Granada, 18016 Granada, Spain; 
      Instituto de Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, 
      Spain; Consortium for Biomedical Research in Epidemiology and Public Health 
      (CIBERESP), Spain; Department of Radiology and Physical Medicine, School of 
      Medicine, University of Granada, 18016 Granada, Spain.
FAU - Schoeters, Greet
AU  - Schoeters G
AD  - VITO Health, Flemish Institute for Technological Research (VITO), 2400, Mol, 
      Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, 
      Belgium.
FAU - Fernandez, Mariana F
AU  - Fernandez MF
AD  - Biomedical Research Center (CIBM), University of Granada, 18016 Granada, Spain; 
      Instituto de Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, 
      Spain; Consortium for Biomedical Research in Epidemiology and Public Health 
      (CIBERESP), Spain; Department of Radiology and Physical Medicine, School of 
      Medicine, University of Granada, 18016 Granada, Spain. Electronic address: 
      marieta@ugr.es.
LA  - eng
PT  - Journal Article
DEP - 20230721
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - 0 (Kisspeptins)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 3XMK78S47O (Testosterone)
RN  - 0 (Environmental Pollutants)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - 0 (Alkanesulfonic Acids)
RN  - 0 (Fluorocarbons)
SB  - IM
MH  - Female
MH  - Humans
MH  - Male
MH  - Adolescent
MH  - Kisspeptins
MH  - Bayes Theorem
MH  - Gonadal Steroid Hormones
MH  - Testosterone
MH  - *Environmental Pollutants
MH  - Follicle Stimulating Hormone
MH  - *Alkanesulfonic Acids
MH  - *Fluorocarbons
OTO - NOTNLM
OT  - Effect biomarkers
OT  - HBM4EU
OT  - Kisspeptin
OT  - PFAS
OT  - Reproductive hormones
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/07/24 00:41
MHDA- 2023/09/18 12:43
CRDT- 2023/07/23 19:28
PHST- 2023/03/20 00:00 [received]
PHST- 2023/06/18 00:00 [revised]
PHST- 2023/07/15 00:00 [accepted]
PHST- 2023/09/18 12:43 [medline]
PHST- 2023/07/24 00:41 [pubmed]
PHST- 2023/07/23 19:28 [entrez]
AID - S0269-7491(23)01216-2 [pii]
AID - 10.1016/j.envpol.2023.122214 [doi]
PST - ppublish
SO  - Environ Pollut. 2023 Oct 15;335:122214. doi: 10.1016/j.envpol.2023.122214. Epub 
      2023 Jul 21.