Repeated Injections of Mesenchymal Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Cavernous Nerve Injury Rat Model.

PURPOSE: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. MATERIALS AND METHODS: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. RESULTS: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. CONCLUSIONS: Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

In vitro study of Organization for Economic Co-operation and Development (OECD) endocrine disruptor screening and testing methods- establishment of a recombinant rat androgen receptor (rrAR) binding assay.

The androgen receptor (AR) binding assay can be used to determine the ability of probable endocrine disruptors (EDs) to compete with synthetic androgen methyltrienolone (R1881) for binding to recombinant rat AR (rrAR). In this study, we assessed AR binding of various chemicals using Lexius Freyberger's method. The rank of relative binding affinity (RBA, IC(50)) on the tested chemicals was trenbolone 1.3 x 10(-8) M (RBA 138) > dihydrotesterone (DHT) 1.8 x 10(-8) M (RBA 100) > methyl testosterone 5.7 x 10(-8) M (RBA 31.6) > nonylphenol (NP) 1.3 x 10(-5) M (RBA 0.14) > bisphenol A (BPA) 1.1 x 10(-4) M (RBA 0.016) > isobutyl paraben 3.1 x 10(-4) M (RBA 0.0058) > butyl paraben 6.2 x 10(-4) M (RBA 0.0029) > propyl paraben 9.7 x 10(-4) M (RBA 0.0019). However, di(n-butyl) phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), known anti-androgenic chemicals, did not show any significant AR binding activity. Our data suggests that in vitro AR binding assay may be useful as a screening tool for potential EDs.