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

• Published in: European journal of endocrinology Vol. 165; no. 4; pp. 579 - 587
• Main Authors: Gaspari, Laura, Paris, Françoise, Philibert, Pascal, Audran, Françoise, Orsini, Mattea, Servant, Nadège, Maïmoun, Laurent, Kalfa, Nicolas, Sultan, Charles
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.10.2011; European Society of Endocrinology
• Subjects: 46, XY Disorders of Sex Development - chemically induced; 46, XY Disorders of Sex Development - epidemiology; Androgen-Insensitivity Syndrome - chemically induced; Biological and medical sciences; Biological Assay; Clinical Study; Cryptorchidism - chemically induced; DNA - genetics; Endocrine Disruptors - adverse effects; Endocrinopathies; Environment. Living conditions; Environmental Exposure; Environmental Pollutants - adverse effects; Estrogens, Non-Steroidal - blood; Europe; Female; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Hypospadias - chemically induced; Infant; Infant, Newborn; Male; Medical sciences; Occupational Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Testosterone - blood; Vertebrates: endocrinology; Europe; Norway, Oslo; Endocrinopathy; Human; Androgen; Pseudohermaphroditism; Idiopathic; Male; Infant; Sexual differentiation disorder; Endocrine disruptor; Congenital disease; Syndrome; Genital diseases; Chemical product; Target tissue resistance; Newborn; Health and environment; Partial; Environment; Fetus; Sex steroid hormone; Endocrinology
• DOI: 10.1530/EJE-11-0580
• ISSN: 0804-4643; 1479-683X

Objective46,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.SubjectsWe 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.MethodsTo 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.ResultsAll 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.ConclusionsOur results indicate that the ‘idiopathic’ PAIS-like phenotype may in some cases be related to EDC contamination during fetal life.