• PMID: 21788424
• Gene Name: NR5A1
• Condition: Infertility
• Association: All the patients had normal SF1 sequence and one patient showed a double polymorphism of MAMLD1
• Population size: 47
• Population details: 47 patients
• Age: 0-1yr
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Cryptorchid, Hypospadias, 46,XY disorders of sex differentiation

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

Gaspari L, Paris F, Philibert P, Audran F, Orsini M, Servant N, Maïmoun L, Kalfa N, Sultan C.

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. FAU - Gaspari, Laura AU - Gaspari L AD - Unité d'Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie 1, Hôpital Arnaud-de-Villeneuve, Montpellier, France. FAU - Paris, Françoise AU - Paris F FAU - Philibert, Pascal AU - Philibert P FAU - Audran, Françoise AU - Audran F FAU - Orsini, Mattea AU - Orsini M FAU - Servant, Nadège AU - Servant N FAU - Maïmoun, Laurent AU - Maïmoun L FAU - Kalfa, Nicolas AU - Kalfa N