title: Neonatal exposure to zearalenone induces long term modulation of ABC transporter expression in testis.
abstract: Mycotoxin zearalenone (ZEN) is a cereal contaminant produced by various species of Fusarium fungi. When interacting with estrogen receptors, ZEN leads to animal fertility disturbances and other reproductive pathologies. Few data are available on the effects of perinatal exposure to ZEN, particularly in the blood-testis barrier. The aim of this study was to assess the impact of ZEN in adult rats exposed neonatally. We focused on the expression and cellular localization of major ABC transporters expressed in adult rat testis, comparing ZEN effects with those of Estradiol Benzoate (EB) neonatal exposure. Dose-dependent and long term modulations of mRNA and protein levels of Abcb1, Abcc1, Abcg2, Abcc4 and Abcc5 were observed, along with Abcc4 protein cellular delocalization. ZEN exposure of SerW3 Sertoli cells showed modulation of Abcb1, Abcc4 and Abcc5. Comparison with EB exposure showed similar modulation profiles for Abcg2 but differential modulations for Abcb1, Abcc1, Abcc4 and Abcc5 in vivo, and a similar profile for Abcb1 modulation by ZEN and EB, but differential modulation for Abcc4 and Abcc5 in vitro. ZEN and EB effects were inhibited by in vitro addition of the pure anti-estrogen ICI 182.780, suggesting the at least partial implication of ZEN estrogenic activity in these modulations. These results suggested that ZEN neonatal exposure could affect the exposure of testis to ABC transporter substrates, and negatively influence spermatogenesis and male fertility.
authors.affiliation: CarMeN, INRA 1235/INSERM 1060/UCBL1/INSA Lyon/HCL, Faculté de Médecine, LYON SUD-BP 12, 165 Chemin du Grand Revoyet, 69921 Oullins Cedex, France.
authors.forename: Farah
authors.initials: F
authors.lastname: Koraïchi
authors.forename: Lilia
authors.initials: L
authors.lastname: Inoubli
authors.forename: Nadjem
authors.initials: N
authors.lastname: Lakhdari
authors.forename: Léo
authors.initials: L
authors.lastname: Meunier
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vega
authors.forename: Claire
authors.initials: C
authors.lastname: Mauduit
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benahmed
authors.forename: Caroline
authors.initials: C
authors.lastname: Prouillac
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Lecoeur
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D000077267:Fulvestrant; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D018528:ATP-Binding Cassette Transporters; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D000077267:Fulvestrant; D004958:Estradiol; D015025:Zearalenone
keywords: 17β estradiol; 4′,6′-diaminido-2-phenylindole; ABC; ABC transporters; ABCB1/Abcb1a-b; ABCC1-5/Abcc1-5; ABCG2/Abcg2; ATP Binding Cassette; ATP Binding Cassette, subfamily B, member 1A-B; ATP Binding Cassette, subfamily C, member 1–5; ATP Binding Cassette, subfamily G, member 2; Actb; Actin, beta; BTB; DAPI; E2; EB; ESR1/Esr1; ESR2/Esr2; ESRs/Esrs; Estradiol Benzoate; Estrogenic xenobiotics; GD; Gapdh; Neonatal exposure; PND; Rat; Sertoli; Testis; ZEN; blood testis barrier; estrogen receptor α; estrogen receptor β; estrogen receptors; gestational day; glyceraldehyde 3-phosphate dehydrogenase; post natal day; zearalenone