Anti-androgenic compounds in breast milk and cryptorchidism among Norwegian boys in the HUMIS birth cohort

Bérénice Collet, Anteneh A. Desalegn, Kees Swart, Matthijs Naderman, Nina Iszatt, Hein Stigum, Tina K. Jensen, Abraham Brouwer*, Merete Eggesbø, Bart van der Burg

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The prevalence of cryptorchidism has increased over the past decades, yet its origins remain poorly understood. Testis descent is dependent on androgens and likely affected by endocrine disrupting compounds (EDCs), targeting the androgen receptor (AR). We investigated the association between anti-androgenic activity, not derived from natural hormones, in maternal breast milk and impaired testis descent among boys. We performed a case-control study based on 199 breast milk samples from 94 mothers of cryptorchid boys and 105 random non-cryptorchid boys participating in the Norwegian HUMIS (Human Milk Study) cohort. For each participant, apolar, and polar fractions were extracted, and combined to reconstitute a mixture. Anti-androgenic activity was measured in all three fractions using the human cell-based in vitro anti-AR CALUX® assay and expressed in μg of flutamide equivalent, a well-known antiandrogen. Results from fraction analyses were compared among boys with cryptorchidism and controls using multiple logistic regression, controlling for appropriate confounders identified using a directed acyclic graph. Children's daily exposure to anti-androgenic EDCs through breastfeeding was estimated to 78 μg flutamide eq./kg of body weigh/day. The activity was higher in the polar fraction (1.48 ± 1.37 μg flutamide eq./g of milk) mainly representing non-persistent chemicals, in contrast to other fractions. However, the activity in the polar extracts was decreased when in mixtures with the apolar fraction, indicating synergistic interactions. No significant difference in the activity was observed according to cryptorchid status for polar, apolar or mixed breast milk fractions. The study showed anti-androgenic activity in nearly all human milk samples, and at levels higher than the advisory threshold. However, no significant association was observed between cryptorchidism and antiandrogenic activity measured in either polar, apolar, or mixture fractions derived from breast milk.

Original languageEnglish
Article number149746
Pages (from-to)1-10
Number of pages10
JournalScience of the Total Environment
Volume803
Early online date26 Aug 2021
DOIs
Publication statusPublished - 10 Jan 2022

Bibliographical note

Funding Information:
This work was supported by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 722634.

Funding Information:
This work was supported by the European Union 's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 722634 .

Publisher Copyright:
© 2021

Keywords

  • Androgen receptor
  • Bioassay
  • Breast milk
  • CALUX
  • Cryptorchidism
  • Human milk

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