Retraction: <i>In utero</i>-exposed di(<i>n</i>-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Abstract

-Female pregnant Sprague-Dawley rats were intragastrically (ig) administered di(n-butyl) phthalate (DBP) at four doses (0, 10, 50 and 100 mg/kg) during gestation days (GD) 12-21 (n = 5 per group). The age-related morphological changes of Leydig cell mitochondrion (LC-Mt) and testosterone biosynthesis enzymes/associated genes/proteins expression levels were investigated. As compared to the control (no DBP), the 10 mg, and 50 mg DBP dose groups, the 100 mg DBP dose group at weeks 5 and 7 showed a significant amount of small LC-Mt. Thereafter, from weeks 9 to 17, the LC-Mt size and quantity in the100 mg DBP dose group increased and became statistically similar to the other dose groups; hence, dose and time-dependent LC-Mt changes were observed. Throughout the study, the 100 mg DBP dose group had significantly lower testosterone levels. In addition, the 100 mg DBP dose group displayed lower StAR (StAR, steroidogenic acute regulatory protein) and P450scc (CYP11a1, cholesterol side-chain cleavage enzyme) levels at weeks 5 and 7, but they became statistically similar to all other dose groups at weeks 9 to 17; in contrast, the SR-B1 (Sarb1, scavenger receptor class B member 1) levels were similar for all DBP dose groups. The rats in utero 100 mg DBP /kg/day (GD 12-21) exposure results from this study indicate a dose-dependent, age-related morphological change in LC-Mt which are linked to reductions in testosterone biosynthesis genes / proteins expression, specifically StAR and P450scc.

Retraction: Quantitative morphometric analysis of vimentin filaments in Sertoli cells of rats after <i>in utero</i> DBP exposure

“…The decrease of Vim in Sertoli cells seemed to be linked to testicular testosterone levels (Wakui et al, 2013;Motohashi et al, 2016). Moreover, the present study also shows that new morphometric methods can be used widely for quantitative analysis of cellular cytoplasmic filaments.…”

“…In the present study, rats in utero were exposed to DBP (intragastrically, 100 mg/kg/day) (Wakui et al, 2013;Motohashi et al, 2016), and the perinuclear volume of Vim microfilaments in Sertoli cells was quantified at 7, 9, 14, and 17 weeks using improved electron microscopy morphometric quantitative analysis techniques.…”

Chlorinated biphenyls effect on estrogen-related receptor expression, steroid secretion, mitochondria ultrastructure but not on mitochondrial membrane potential in Leydig cells

“…Histomorphological analysis of rat testes after exposure to di(n-butyl) phthalate revealed an increased Leydig cell number that showed swollen mitochondria (Ha et al 2016 ). In animals, exposed to di(n-butyl) phthalate in utero , dose-dependent and age-related changes of Leydig cell mitochondria morphology, function and associated proteins were observed (Motohashi et al 2016 ). Also, in tumors, Leydig cell organophosphate flame retardants affected mitochondrial activity, cell survival and superoxide production (Schang et al 2016 ).…”

In Utero Exposure to Di(n-butyl)phthalate Induces Morphological and Biochemical Changes in Rats Postpuberty

“…The testicular T levels via the DBP treatment group were significantly lower (p < .05) than the control group at all 4 time points (i.e., weeks 7, 9, 14, and 17; Figure 1I). We previously demonstrated that in utero DBP exposure decreased T levels by causing dysfunction of Leydig cells Wempe, Mutou, Okayama, et al 2016;. Testicular T is a determinant of spermatogenesis, which binds with the androgen-binding protein of Sertoli cells to produce glycoprotein (b globulin).…”