RESUMEN
Previous studies show that prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure induces premature testicular aging. However, the evidence is weak, and the underlying mechanisms remain unclear. p38/extracellular signal-regulated kinase (ERK)/c-Jun NH(2)-terminal kinase (JNK) MAPK pathways participate in aging. Leydig cell (LC) senescence results in testicular aging. Whether prenatal DEHP exposure induces premature testicular aging by promoting LC senescence warrants further study. Here, male mice undergo prenatal exposure to 500 mg per kg per day DEHP, and TM3 LCs are treated with 200 µm mono (2-ethylhexyl) phthalate (MEHP). MAPK pathways, testicular toxicity, and senescent phenotypes (ß-gal activity, p21, p16, and cell cycle) of male mice and LCs are explored. Prenatal DEHP exposure induces premature testicular aging in middle-aged mice (poor genital development, reduced testosterone synthesis, poor semen quality, increased ß-gal activity, and upregulated expression of p21 and p16). MEHP induces LCs senescence (cell cycle arrest, increased ß-gal activity, and upregulated expression of p21). p38 and JNK pathways are activated, and the ERK pathway is inactivated. In conclusion, prenatal DEHP exposure induces premature testicular aging by promoting LC senescence through MAPK signaling pathways.
RESUMEN
The existing regulations and systems of the Swedish Medical Products Agency (MPA) have clear provisions on the definition, classification and listed on the market procecure of pharmaceutical products, and the supervision strictly follows the EU standards. Traditional Chinese Medicine (TCM) products belong to the category of Swedish Herbal Medicine Products (HMP) or Traditional Herbal Medicine Products (THMP) and are under the supervision of Swedish Pharmaceutical Products Administration (MPA). This paper analyzes the classification, relevant regulations and registration procecures of TCM products in Sweden. It is suggests that TCM enterprises should fully understand the EU regulations and guidance regulations before listed on the market of TCM products. They should also clarify the product category, and provide sufficient and accurate evidence. In the application process, they should pay attention to strengthening communication with the drug administration units of Sweden.