title: 'Idiopathic' partial androgen insensitivity syndrome in 28 newborn and infant males: impact of prenatal exposure to environmental endocrine disruptor chemicals?
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Unité d'Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie 1, Hôpital Arnaud-de-Villeneuve, Montpellier, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Gaspari
authors.forename: Françoise
authors.initials: F
authors.lastname: Paris
authors.forename: Pascal
authors.initials: P
authors.lastname: Philibert
authors.forename: Françoise
authors.initials: F
authors.lastname: Audran
authors.forename: Mattea
authors.initials: M
authors.lastname: Orsini
authors.forename: Nadège
authors.initials: N
authors.lastname: Servant
authors.forename: Laurent
authors.initials: L
authors.lastname: Maïmoun
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kalfa
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
mesh_terms: D013734:Androgen-Insensitivity Syndrome / Q000139:chemically induced*; D001681:Biological Assay; D003456:Cryptorchidism / Q000139:chemically induced; D004247:DNA / Q000235:genetics; D058490:Disorder of Sex Development, 46,XY / Q000139:chemically induced / Q000453:epidemiology; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000009:adverse effects*; D004968:Estrogens, Non-Steroidal / Q000097:blood; D005060:Europe; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007021:Hypospadias / Q000139:chemically induced; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016273:Occupational Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013739:Testosterone / Q000097:blood
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D013739:Testosterone; D004247:DNA