[Study of Pregnancy Exposure to PFOS on Reproductive Toxicities and Mechanism in Male Offspring Rats].

OBJECTIVE: To explore the effects of testosterone synthesis in adult leydig cell (ALC) of male rats exposed by perfluorooctane sulfonate (PFOS) during pregnancy. METHODS: At gestations 12 day, the pregnant rats were exposed to PFOS (5 mg/kg, PFOS group) or 0.5% Tween (control group) by gavage, once a day for 8 consecutive days. On postnatal day (PND) 70, several indexes of male offspring rats were measured including body mass, testicular coefficient, sperm count, serum testosterone concentration. The mRNA levels of ALC associated with testosterone synthesis were detected by real-time quantitative RT-PCR. RESULTS: The result showed that sperm count and serum testosterone concentration decreased in male offspring rats of PFOS group (P < 0.05), and body mass was significantly lower (P < 0.001). The expression of steroidogenic acute regulatory factor (Star), scavenger receptor class B type 1 (Scarb1), Cyp11a1 (coding gene of cytochrome P450 side chain cleavage) and Hsd17b3 (coding gene of 17ß-hydroxysteroid dehydrogenase) were down regulated (P < 0.05), no significant statistical difference was observed on the mRNA level of insulin-like growth factor-1 (Igf1) and insulin-like factor 3 (Insl3). CONCLUSION: Gestational exposure to PFOS can inhibit the mRNA levels associated with testosterone synthesis, and decrease the ability of testosterone synthesis in ALC of male offspring rats.

Hydroxysafflor yellow A induces apoptosis in activated hepatic stellate cells through ERK1/2 pathway in vitro.

A key feature in the molecular pathogenesis of liver fibrosis requires maintenance of the activated hepatic stellate cells (HSCs) phenotype by inhibition of apoptosis. The induction of apoptosis in activated HSCs has been proposed as an antifibrotic treatment strategy. This study aims at evaluating the effect of hydroxysafflor yellow A (HSYA) on apoptosis of culture-activated HSCs and further elucidating the underlying mechanisms. Primary HSCs were isolated from rats. The analysis of the cell cycle be performed by flow cytometry, detection of apoptosis by Annexin V-FITC/ PI staining, and the results were confirmed by DNA fragmentation, and cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Real-time polymerase chain reaction and Western blotting were used to analyze the expression of genes. Our results revealed that HSYA significantly induced apoptosis in a dose- and time-dependent manner. HSYA suppresses the activation of ERK1/2 and ERK1/2-regulated gene expression, including Bcl-2, Cytochrome c, caspase-9, and caspase-3, leading to the enhancement of apoptosis. Pharmacological blockade of ERK1/2 kinase abrogation this action of HSYA. Our data provide a molecular basis for the anti-hepatic fibrosis activity of HSYA.