Pre and postnatal exposure to mercury and sexual development in 9-year-old children in Spain: The role of brain-derived neurotrophic factor

Environ Res. 2022 Oct:213:113620. doi: 10.1016/j.envres.2022.113620. Epub 2022 Jun 10.


Early exposure to mercury has been related to endocrine disruption. Steroid hormones play a crucial role in neural cell migration, differentiation, etc., as well as protecting against several neurotoxic compounds. We investigate the relation between mercury exposure and children's sexual development, and we evaluate the possible influence of different brain-derived neurotrophic factor (BDNF) polymorphisms on this association. Our study sample comprised 412 9-year-old children participating in the INMA cohort (2004-2015). Mercury concentrations were measured at birth (cord blood) and at 4 and 9 years of age (hair). Sexual development was assessed by levels of sex steroid hormones (estradiol and testosterone) in saliva and the Tanner stages of sex development at 9 years (categorized as 1: prepuberty and >1: pubertal onset). Covariates and confounders were collected through questionnaires during pregnancy and childhood. Polymorphisms in the BDNF gene were genotyped in cord blood DNA. Multivariate linear regression analyses were performed between mercury levels and children's sexual development by sex. Effect modification by genetic polymorphisms and fish intake was assessed. We found marginally significant inverse associations between postnatal exposure to mercury (at 9 years) and testosterone levels (β[95%CI] = -0.16[-0.33,0.001], and -0.20[-0.42,0.03], for boys and girls, respectively). Additionally, we found that prenatal mercury was negatively associated with Tanner stage >1 in boys. Finally, we found significant genetic interactions for some single nucleotide polymorphisms in the BDNF gene. In conclusion, pre and postnatal exposure to mercury seems to affect children's sexual development and BDNF may play a role in this association, but further research would be needed.

Keywords: BDNF; Birth cohort; Childhood; Mercury exposure; Steroid hormones; Tanner stages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Child
  • Diet / statistics & numerical data
  • Female
  • Fishes
  • Humans
  • Mercury Poisoning
  • Mercury* / adverse effects
  • Mercury* / analysis
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Sexual Development
  • Spain
  • Testosterone


  • Brain-Derived Neurotrophic Factor
  • Testosterone
  • Mercury