JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATI C AGENTS Voi. 27, no . 3, 805-81 6 (20 13) TOXICITY OF CADMIUM ON SERTOLI CELLS FUNCTIONAL COMPETENCE : AN IN V ITROSTUDY G. LUCN, C. LILLI 1 , C. BELLUCCI 1 , F. MANCUS0 1 , M. CALVITTI 1 , I. ARAT0 1 , G. FALABELLA 1 , S. GIOVAGNOLP, M.C. AGLIETTP, A. LUMARE 4 , G. MUZI5 , R. CALAFIORE 3 and M. BOD0 1 1 Department of Experimental Medic in e and Biochemical Sciences, Uni versity of Perug ia, Perugia, Italy; 2 Department of Pharmaceuticaf Sciences, University of Perugia, Perugia, Jtal y,· 3 Department of Internal Medicine, Univers ity of Perugia, Perugia, Italy; 4 Specia li st in Occupational Medicine, Perugia, Jt al y,· 5 Section of Occupational Medicine, Resp iratory Diseases and To xicology, University of Perugia, Italy; Received March 24, 2013 -Acce pted June 25, 2 01 3 G. Luca, C. Lilli and C. Bellucci equally contributed to this paper. R. Calafìore and M. Bodo share senior authorship to thi s paper. Cadmium (Cd), an ubiquitous environmental metal, mainly used for industriai purposes , ma y be toxic at level ofthe reproductive system. Testis tubular-based Sertoli cells (SC), play a major role in constituting the blood-testis barrier and provide a unique microenvironment for the genesis and differentiation of germ cells. Hence SC strictly control sperm qu alitative and quantitative parameters. We aimed to assess whether exposure to Cd would ad versely affect sup e rior mammal SC viability and function. We isolated and purified SC from pre-pubertal pig testes according to our method and incubated the retriev ed cells with three different Cadmium chloride conce ntrations (5-10-15 μM ). Param eter s of SC function such as inhibin B and anti-Mullerian hormone (AMH) were depressed by Cd exposure, contrary to w hat observed in untreated controls. No impairment of the FSH receptor integrit y on the SC, as assessed by 17-P-estradiol production, upon stimulation with FSH, was observed in either 5 μM Cd-treated or untreated controls. Differences, on the contrary, were observed for higher Cd concentrations (10 and 15 mM), in terms ofFSH receptor integrity, that was altered, as compared to untreated controls, in term s of lower production of 17-P-estradiol. In addition, th e apoptotic test showed a significant increase of earl y (ANNEXIN V- /Propidium lodide+) (AV-/PI+) and late apoptotic cell s (AV+/ PI+) in ali Cd -treated SC conditions as compared to controls. In conclusion, the Cd -related toxicity on SC, clearly demonstr ated by our stud y, even at low concentrations, is expected to damage spermatogenesis that directly is depend e nt upon retention of se viability and function. Cd, an ubiquitous environmental pollutant, is a common heavy toxin mostly derived from industria! activities, that causes severe toxicity in various organs including the testi s (1- 7). Cd toxicity results, in fact, in severe irnpairment of the male genn ce ll s both in rodents (8, 9, 4) and humans, often le ading to Key words: Cadmium, Serto/i cells, jìmction Mailing address: Prof. Riccardo Cala fì ore, Depm tment of Intern al Medicine, Via Enrico Dal Pozzo, University of Perugia, 06 126, Perugia, lt aly Te l. : +39 0744 205454 Fax: +39 075 5730855 e-mail: is let@unipg.it 805 0393-974X (20 13) Copyright CO by BIOLI FE, s.a.s. Thìs publication and/or article is for individuai use only and may not be further reproduced without written penn ission from the copy ri g ht holder. Unauth o ri zed reproduction may result in financial and o th er penalties DISCLOSU RE: ALL AUT HORS REPORT NO CONF LI CTS or I NTE REST RELE VANT TO T HI S ART IC LE.