Urinary concentration of phthalates and bisphenol A during minipuberty is associated with reproductive hormone concentrations in infant boys

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Fulltext

    Forlagets udgivne version, 1,74 MB, PDF-dokument

  • Matilde Lærkeholm Müller
  • Alexander Siegfried Busch
  • Marie Lindhardt Ljubicic
  • Emmie N. Upners
  • Margit B. Fischer
  • Casper P. Hagen
  • Jakob Albrethsen
  • Hanne Frederiksen
  • Juul, Anders
  • Anna Maria Andersson

Background: The transient postnatal activation of the hypothalamic-pituitary-gonadal hormone axis is termed minipuberty and considered an important developmental period, which is highly sensitive to endocrine disruption. Here, we explore exposure-outcome associations during minipuberty between concentrations of potentially endocrine disrupting chemicals (EDCs) in urine of infant boys and their serum reproductive hormone concentrations. Methods: In total, 36 boys participating in the COPENHAGEN Minipuberty Study had data available for both urine biomarkers of target endocrine disrupting chemicals and reproductive hormones in serum from samples collected on the same day. Serum concentrations of reproductive hormones were measured by immunoassays or by LC-MS/MS. Urinary concentrations of metabolites of 39 non-persisting chemicals, including phthalates and phenolic compounds, were measured by LC-MS/MS. Nineteen chemicals had concentrations above the limit of detection in ≥50% of children and were included in data analysis. Associations of urinary phthalate metabolite and phenol concentrations (in tertiles) with hormone outcomes (age- and sex-specific SD-scores) were analysed by linear regression. Primarily, we focused on the EU regulated phthalates; butylbenzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di-(2-ethylhexyl) phthalate (DEHP) as well as bisphenol A (BPA). Urinary metabolites of DiBP, DnBP and DEHP were summed and expressed as ∑DiBPm, ∑DnBPm and ∑DEHPm. Results: Compared to boys in the lowest ∑DnBPm tertile, urinary concentration of ∑DnBPm was associated with concurrent higher luteinizing hormone (LH) and anti-Müllerian hormone (AMH) SD-scores as well as lower testosterone/LH ratio in boys in the middle ∑DnBPm tertile (estimates (CI 95%) 0.79 (0.04; 1.54), 0.91 (0.13; 1.68), and −0.88 (−1.58;-0.19), respectively). Further, higher insulin-like peptide 3 (INSL3) SD-scores and lower DHEAS SD-score in boys in the highest ∑DnBPm tertile (0.91 (0.12; 1.70) and −0.85 (−1.51;-0.18), respectively) were observed. In addition, boys in the middle and highest ∑DEHPm tertile had higher LH (1.07 (0.35; 1.79) and 0.71 (−0.01; 1.43), respectively) and in the highest ∑DEHPm tertile also higher AMH (0.85 (0.10; 1.61)) concentration SD-scores, respectively. Boys in the highest BPA tertile had significantly higher AMH and lower DHEAS concentration compared to boys in the lowest BPA tertile (1.28 (0.54; 2.02) and −0.73 (−1.45; −0.01)), respectively. Discussion: Our findings indicate that exposure to chemicals with known or suspected endocrine disrupting potential, especially the EU-regulated DnBP, DEHP and BPA, may modify male reproductive hormone concentrations in infant boys suggesting that minipuberty is a critical window sensitive to endocrine disruption.

OriginalsprogEngelsk
Artikelnummer114166
TidsskriftInternational Journal of Hygiene and Environmental Health
Vol/bind250
ISSN1438-4639
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
A special thank you to the participating infants and their parents and to the colleagues who collected these data. The COPENHAGEN Minipuberty Study received support from the Candy Foundation , Nos. 2017–224 and 2020–344 (ENU); Absalon Foundation , No. F- 23653–01 (MLL); The European Union's Horizon 2020 research and innovation program, No. 733032 HBM4EU (AMA); The Danish Environmental Protection Agency (Miljøstyrelsen: MST- 621- 00012 Center on Endocrine Disrupters) (AJ, HF); The Research council of Capital Region of Denmark: No. E- 22717–11 (AJ); Research council of Rigshospitalet: Nos. E- 22717–12, E- 22717–07, E- 22717–08 (AJ, ASB, CEK, MLL); Aase og Ejnar Danielsens Fond: No. 10–001874 (AJ); International Research and Research Training Centre for Male Reproduction and Child Health (EDMaRC): No. 1500321/1604357 (ASB). Chemical analyses and data analyses for this sub-study of the Copenhagen Minipuberty study were funded by the Danish Centre on Endocrine Disruptors through a contract with the Danish EPA ( MST-611-00012 ). ASB was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 464240267 .

Publisher Copyright:
© 2023 The Authors

ID: 344647153