MiR-301b-3p/3584-5p enhances low-dose mono-n-butyl phthalate (MBP)–induced proliferation by targeting Rasd1 in Sertoli cells

Cross Sectional Study on Exposure to BPA and Phthalates and Semen Parameters in Men Attending a Fertility Center

“…To use as a model for human testicular dysgenesis syndrome, pregnant rats were exposed to DnBP and a suppression of intratesticular testosterone, a focal aggregation of Leyding cells and ectopic Sertoli cells were obtained [27]. Also, the possible molecular mechanism of MnBP was investigated in vitro and even at low dose, an increased Sertoli cells proliferation emerged [28].Among other chemicals, evidence from previous studies showed that also bisphenol A (BPA), a precursor to important plastics like polycarbonates and epoxy resins, could interact with the endocrine system [29,30] and semen quality as well [31,32] even if the present evidence is controversial.According to Lassen et al [33] the association between BPA levels and reproductive hormones would support an anti-androgenic effect with deleterious consequences on motile spermatozoa (−6.7%, confidence interval-CI −11.76/1.63 95%), data confirmed also by Radwan et al [34].BPA induced, in in vivo studies, testicular dysfunction and alteration of Sertoli cell viability [35], testicular apoptosis in male rats [36]; after BPA exposure spermatogenic cells were disorganized and degenerated, spermatids had fragmented pyknotic nuclei and a significant decrease in the rate of proliferation of germ cells was present [37].In an epidemiological survey on 215 young health adults, the urinary BPA levels were significantly and inversely associated with sperm concentration and total sperm count [38]. In recent surveys [39,40] sperm concentration, morphology and motility were negatively associated with BPA urinary levels.…”

“…To use as a model for human testicular dysgenesis syndrome, pregnant rats were exposed to DnBP and a suppression of intratesticular testosterone, a focal aggregation of Leyding cells and ectopic Sertoli cells were obtained [27]. Also, the possible molecular mechanism of MnBP was investigated in vitro and even at low dose, an increased Sertoli cells proliferation emerged [28].…”

Dibutyl phthalate promotes juvenile Sertoli cell proliferation by decreasing the levels of the E3 ubiquitin ligase Pellino 2

“…Based on microarray data in the GEO (Gene Expression Omnibus) database from our previous report [9], Peli2 was chosen for further study because of its important role in cell proliferation. We demonstrated that prenatal exposure to DBP (50 mg/kg/day) reduced the levels of Peli2 in the mouse testes, as shown by immunohistochemical staining (Fig.…”

“…Some studies confirmed that in utero exposure to DBP caused testicular malformations in male offspring [3][4][5], but the underlying mechanism has not yet fully investigated. As one of the target cells of DBP/MBP [5][6][7][8][9], Sertoli cells (SCs) are the first that are recognized to differentiate in the foetal indifferent gonad, and they play a critical role in foetal testis formation and sexual differentiation as well as in adult spermatogenesis [10][11][12]. Because of the fixed number of germ cells supported by SCs, the proliferative capability of immature SCs during prepuberty determines the number of mature SCs, testis size and output of germ cells in the mature testis.…”

“…Because of the fixed number of germ cells supported by SCs, the proliferative capability of immature SCs during prepuberty determines the number of mature SCs, testis size and output of germ cells in the mature testis. Our recent study suggested that monobutyl phthalate (MBP), the metabolite of DBP, could disrupt the growth of juvenile SCs [9], however, the underlying molecular mechanism still needs to be further explored.…”