'Idiopathic' partial androgen insensitivity syndrome in 28 newborn and infant males: impact of prenatal exposure to environmental endocrine disruptor chemicals?

Eur J Endocrinol. 2011 Oct;165(4):579-87. doi: 10.1530/EJE-11-0580. Epub 2011 Jul 25.


Objective: 46,XY disorders of sex differentiation (46,XY DSD) can be due to a testis determination defect, an androgen biosynthesis defect, or androgen resistance (complete or partial androgen insensitivity syndrome (PAIS), or 5α reductase deficiency). We aimed to evaluate the impact of a prenatal contamination by environmental xenoestrogens in 'idiopathic' PAIS-like phenotype.

Subjects: We investigated 28 newborn/infant males with 46,XY DSD, normal androgen production, and no androgen receptor or steroid-5αR type II enzyme (SRD5A2) gene mutations.

Methods: To exclude other genetic defects, we sequenced the steroidogenic factor 1 (SF1) and mastermind-like domain-containing 1 (MAMLD1) genes, which were recently found to be associated with the PAIS-like phenotype. Parents were interviewed about their environmental/occupational exposure to endocrine disrupting chemicals (EDCs) before/during the patients' fetal life. Total estrogenic bioactivity of patient serum was analyzed by ultrasensitive bioassay.

Results: All the patients had normal SF1 sequence and one patient showed a double polymorphism of MAMLD1. Eleven (39.3%) of the 28 patients had reported parental fetal exposure to EDCs. The mean estrogenic bioactivity in these 11 patients with fetal EDC exposure (6.65 ± 8.07 pg/ml) versus 17 cases without contamination (1.27 ± 0.34 pg/ml) and controls (1.06 ± 0.44 pg/ml; P<0.05) was elevated.

Conclusions: Our results indicate that the 'idiopathic' PAIS-like phenotype may in some cases be related to EDC contamination during fetal life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen-Insensitivity Syndrome / chemically induced*
  • Biological Assay
  • Cryptorchidism / chemically induced
  • DNA / genetics
  • Disorder of Sex Development, 46,XY / chemically induced
  • Disorder of Sex Development, 46,XY / epidemiology
  • Endocrine Disruptors / adverse effects*
  • Environmental Exposure
  • Environmental Pollutants / adverse effects*
  • Estrogens, Non-Steroidal / blood
  • Europe
  • Female
  • HeLa Cells
  • Humans
  • Hypospadias / chemically induced
  • Infant
  • Infant, Newborn
  • Male
  • Occupational Exposure
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Testosterone / blood


  • Endocrine Disruptors
  • Environmental Pollutants
  • Estrogens, Non-Steroidal
  • Testosterone
  • DNA