title: Endocrine effects of lifelong exposure to low-dose depleted uranium on testicular functions in adult rat.
abstract: Environmental toxicant exposure can induce disorders in sex steroidogenesis during fetal gonad development. Our previous study demonstrated that chronic adult exposure to a supra environmental concentration of depleted uranium (DU) does not impair testicular steroidogenesis in rats. In this study, we investigated the effects of lifelong exposure (embryo - adult) to low-dose DU (40 or 120mgL-1) on adult rat testicular steroidogenesis and spermatogenesis. A significant content of uranium was detected in testis and epididymis in the DU 120mgL-1group and the assay in epididymal spermatozoa showed a significant content in both groups. No major defect was observed in testicular histology except a decrease in the number of basal vacuoles in the DU groups. Moreover, plasma Follicle-Stimuling Hormone [FSH] and Luteinizing Hormone [LH] levels were increased only in the DU 120mgL-1group and intratesticular estradiol was decreased in both groups. Testosterone level was reduced in plasma and testis in the DU 40mgL-1group. These modulations could be explained by an observed decrease in gene expression of luteinizing hormone receptor (LHR), and enzymes involved in steroid production and associated signal transduction (StAR, cyp11a1, cyp17a1, 3βhsd, 17βhsd, TGFβ1, AR). Several genes specific to germ cells and cell junctions of the blood-testis barrier were also modulated. In conclusion, these data show that fetal life is a critical window for chronic uranium exposure and that the endocrine activities of low-dose uranium could disrupt steroidogenesis through the hypothalamic-pituitary-testicular axis. Further investigation should be so useful in subsequent generations to improve risk assessment of uranium exposure.
authors.affiliation: Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et SÛreté Nucléaire, B.P.17, 92262 Fontenay aux Roses Cedex, France. Electronic address: audrey.legendre@irsn.fr.
authors.forename: Audrey
authors.initials: A
authors.lastname: Legendre
authors.affiliation: Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et SÛreté Nucléaire, B.P.17, 92262 Fontenay aux Roses Cedex, France. Electronic address: christelle.elie@irsn.fr.
authors.forename: Christelle
authors.initials: C
authors.lastname: Elie
authors.affiliation: Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et SÛreté Nucléaire, B.P.17, 92262 Fontenay aux Roses Cedex, France. Electronic address: camilleramambason@gmail.com.
authors.forename: Camille
authors.initials: C
authors.lastname: Ramambason
authors.affiliation: Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et SÛreté Nucléaire, B.P.17, 92262 Fontenay aux Roses Cedex, France. Electronic address: line.manens@irsn.fr.
authors.forename: Line
authors.initials: L
authors.lastname: Manens
authors.affiliation: Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et SÛreté Nucléaire, B.P.17, 92262 Fontenay aux Roses Cedex, France. Electronic address: maamar.souidi@irsn.fr.
authors.forename: Maamar
authors.initials: M
authors.lastname: Souidi
authors.affiliation: UMR- PRC INRA, Centre INRA de Val de Loire, 37380 NOUZILLY, France. Electronic address: pfroment@tours.inra.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Froment
authors.affiliation: Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et SÛreté Nucléaire, B.P.17, 92262 Fontenay aux Roses Cedex, France. Electronic address: karine.tack@irsn.fr.
authors.forename: Karine
authors.initials: K
authors.lastname: Tack
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000187:drug effects / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D014501:Uranium / Q000097:blood / Q000633:toxicity*
chemical_list: D013739:Testosterone; D014501:Uranium; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: Depleted uranium; Hypothalamic-pituitary-testicular axis; Spermatogenesis; Steroidogenesis