title: Exposure and effective dose biomarkers for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in infertile subjects: preliminary results of the PREVIENI project.
abstract: Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have been used as surfactants in various industry and consumer products. PFOS/PFOA are very persistent in the environment and bioaccumulate in humans. They are potential reproductive and developmental toxicants and are considered to be emerging endocrine disrupters (EDs). The Italian project PREVIENI, funded by the Italian Environment Ministry, aims to link environment and human health through the investigation of selected endocrine disrupters (EDs) exposure and associated biomarkers related to human infertility conditions. In the early PREVIENI phase, PFOS and PFOA were determined in 53 couples affected by an infertility status, enrolled in a metropolitan area, according to established inclusion criteria and informed consensus. Nuclear receptors related to chemical compounds interactions were selected as biomarkers of effect and their gene expression modulations were analyzed in human peripheral blood mononuclear cell (PBMC). Among couples, subjects not presenting infertility factors (IF--) were separated from affected subjects (IF++). Most IF-- serum samples showed PFOS and PFOA concentrations overlapping the limit of detection (LOD) of 0.5 ng/g wet weight (ww). A substantial percentage of IF++ serum samples showed PFOS concentrations >20-fold the LOD, i.e. from 3 to 50 ng/g ww. In male (50%, n=26) and from 3 to 144 ng/g ww in female (37%, n=30) samples. PFOA values were below the LOD levels in 90% of the total samples. Peroxisome proliferator-activated receptor-gamma (PPARγ) and aryl hydrocarbon receptor (AhR) showed a low level of expression in PBMC of both IF++ and IF-- groups. Whereas alpha and beta estrogen receptors (ERα and ERβ), androgen receptor (AR), and pregnane X receptor (PXR) were all upregulated in IF++ of both sexes with respect to IF-- group. Our preliminary results related to the metropolitan area indicate that subjects affected by infertility factors tend to have both higher PFOS levels and higher gene expression of specific nuclear receptors.
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy. cinzia.larocca@iss.it
authors.forename: Cinzia
authors.initials: C
authors.lastname: La Rocca
authors.forename: Eva
authors.initials: E
authors.lastname: Alessi
authors.forename: Bruno
authors.initials: B
authors.lastname: Bergamasco
authors.forename: Donatella
authors.initials: D
authors.lastname: Caserta
authors.forename: Francesca
authors.initials: F
authors.lastname: Ciardo
authors.forename: Emiliano
authors.initials: E
authors.lastname: Fanello
authors.forename: Silvano
authors.initials: S
authors.lastname: Focardi
authors.forename: Cristiana
authors.initials: C
authors.lastname: Guerranti
authors.forename: Laura
authors.initials: L
authors.lastname: Stecca
authors.forename: Massimo
authors.initials: M
authors.lastname: Moscarini
authors.forename: Guido
authors.initials: G
authors.lastname: Perra
authors.forename: Sabrina
authors.initials: S
authors.lastname: Tait
authors.forename: Carlo
authors.initials: C
authors.lastname: Zaghi
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000293:Adolescent; D000328:Adult; D017738:Alkanesulfonic Acids / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002210:Caprylates / Q000097:blood*; D016022:Case-Control Studies; D052244:Endocrine Disruptors / Q000097:blood; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring / Q000379:methods; D062665:Epidemiological Monitoring; D005260:Female; D005466:Fluorocarbons / Q000097:blood*; D015870:Gene Expression; D006801:Humans; D007247:Infertility, Female / Q000139:chemically induced* / Q000453:epidemiology; D007248:Infertility, Male / Q000139:chemically induced*; D007558:Italy / Q000453:epidemiology; D008297:Male; D016133:Polymerase Chain Reaction; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood* / Q000235:genetics; D011987:Receptors, Steroid / Q000097:blood; D017678:Sex Distribution; D055815:Young Adult
chemical_list: D017738:Alkanesulfonic Acids; D015415:Biomarkers; D002210:Caprylates; D052244:Endocrine Disruptors; D005466:Fluorocarbons; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid