Abstract
Zearalenone (ZEA) is a non-steroidal xenoestrogen mycotoxin produced by many Fusarium fungal species, which are common contaminants of cereal crops destined for worldwide human and animal consumption. ZEA has been reported in various male reproduction dysfonctions, including decreased fertility potential. In this report, the direct effect of ZEA on the immature Sertoli TM4 cell line was evaluated. The results show that high concentrations of ZEA increase reactive oxygen species via the activation of MAPK signaling. Transcriptome analysis was performed on the TM4 cell line treated with ZEA, and genes involved in sex differentiation (Fgfr2, Igf1, Notch1, Sox9) and extracellular matrix (ECM) formation (Ctgf, Fam20a, Fbn1, Mmp9, Postn, Sparcl1, Spp1) were identified at the center of the functional protein association network, suggesting that ZEA could be detrimental to the early steps of Sertoli cell differentiation.
Highlights
Sertoli cells are involved in testis biology and in the spermatogenesis process
The subsequent proliferation of immature Sertoli cells until puberty determines sperm production capacity through adulthood, as each Sertoli cell is only able to sustain a limited number of germ cells, as the essential role of each Sertoli cell is to regulate germ cell number [2]
It was proposed that E2 might interact with ESR1 in immature Sertoli cells to activate cell proliferation and with ESR2 to induce differentiation
Summary
Sertoli cells are involved in testis biology and in the spermatogenesis process. During the testis development stage, Sertoli cells initiate the sex-specificity differentiation and coordinate the process of sex determination [1]. Estradiol (E2) and its three receptors (ESR1, ESR2 and G protein-coupled estrogen receptor 1-GPER1) play a crucial role in the differentiation and maturation processes of Sertoli cells and in the maintenance of homeostasis. The importance of neonatal estrogen-mediated ESR1 signaling for spermatogenesis was confirmed using a nonresponsive ESR1 knockin mouse model [6], while GPER1 has been shown to regulate apoptosis in Sertoli cells [7]. These experiments suggest that estrogenic activity must be tightly regulated in the testis and in the Sertoli cells. 22..1Rno. eTnusMmuTl4MtbsIem4rmcoaeftlulgreveSiramerbtoiclliietClyles,ll.cLeTilnMlesI4fsrScoeemnllssiitmidveemtroiavZteEudArefrBoAmLBSec/rmtoilciecewllesr.eTtoreaanteadlywzeitthheinecfrfee to ecsetPnarbtolrilasifhteirpoartnoiospneorofsfZpSeeErrmtAoali(toc0eg.lel1sn,de1sui0sr,i,na2gs0pe,ar4ec0ph,uS8be0errtoatalnil dcteesl1lti0cca0unlμaorMndley)vsfeuoloprpp2mo4rethnat.diAseafisnkseehdyoenwluemmnbeinenrt Figure of ginercmrecaeslles., TnMot cseigllsndifeircivaendt,frionmcSeelrltovliiaceblillsi.tTyo wanaaslyzoebtsheerevfefedct aotf Z1E0AμoMn T, Mw4hciellel a sign viacbrieliatys,eceilnlscfyrotmoviimabmialittuyrewBaAsLoBbc/smerivceedwearte atrecaotnedcewnitrhaitnicorneaosifn4g0coμnMcenotrahtiiognhser and of ZZEEAA(0w. 1a,s10e,s2t0im, 4a0,te8d0 aantd71800μμMM.) fTohr e24ohb.sAesrvsheodwZnEinAFidgoursee1e, fafeslcigt hwt ianscrceoasnes, istent t nceysotttpiiotmsvryieiagawvtnbeiiidaofilisctuayatasnw7lfty8f,aesμiocnMobtebcs.edseTellrrhavvveteeia1oddbb0aisbltμeiytaryMvcLewodon[a2ncZse2gEno]Atberostardetairoaovls.ntee[dao2enf5faf4t]ee0c1bvtμ0uewMμntaMdoslori,cfwhowfienghershrisilseectfreroaanonntsmdcitgoetnonhtihetfithrecIaCeaotnr5ni0toegodnrpfeorZaceurfEvepfAiaeosscuwetisneailnydswshtaicrhtinc obs[e2r1v]e.d by Long et al [25] but differs from other groups in which cytoviability was affected at 10 μM [22] or at an even lower concentration affected starting at 1 μM [21]
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