[Effects of organochloride pesticides on dyslipidemias].

Dyslipidemias is one important risk factor associated with chronic diseases. Persistent organic pollutants are resistant to degradation and can be bio-accumulated and magnified through the food chain. Recently, the relation between dyslipidemias and organochlorine pesticides has attracted more attentions. In this review, we explored the distribution of organochloride pesticides in the environment and human body, as well as the possible underlying mechanisms of the association between dyslipidemias and organochloride pesticides, including accumulation and release of organochloride, simulation of estrogen, impact on PPARs, the metabolic fingerprint, and the inflammatory reaction.

Transforming growth factor-ß1 regulates the nascent hematopoietic stem cell niche by promoting gluconeogenesis.

The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-ß1 in the metabolic niche of HSC emergence using the tgf-ß1b-/- zebrafish. Our findings first showed that Tgf-ß1 transcripts were enriched in the nascent HSCs. Loss of tgf-ß1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-ß1b+ cells were runx1+ HSCs and underwent an endothelial-to-hematopoietic-transition process. Although the autocrine of Tgf-ß1 in HSCs rather than endothelial cells was highly demanded to regulate HSC generation, we found that tgf-ß1b promoted HSC emergence through the endothelial c-Jun N-terminal kinase/c-Jun signaling. Chromatin immunoprecipitation (ChIP)-sequencing data showed that tgf-ß1b/c-Jun targeted g6pc3 of FoxO signaling to promote gluconeogenesis and maintain a high glucose level in the niche. Furthermore, loss of tgf-ß1b increased the endoplasmic-reticulum stress and oxidative stress by disturbing metabolic homeostasis. Adding a low dose of TGF-ß1 protein could promote the differentiation of mouse embryonic stem cells towards HSCs in vitro. Altogether, our study provided insights into a new feature of TGF-ß1 in the regulation of glucose metabolism and nascent HSC niche, which may contribute to therapies of hematological malignancies.

Lack of association between polymorphisms in p53 gene and spermatogenetic failure in a Chinese population.

Although various genetic factors have been demonstrated in human male infertility, many genetic causes involving gene variants for the idiopathic male infertility have not yet been elucidated. P53 gene is involved in the meiosis of the male rat and mice, which suggested that p53 plays a critical role in spermatogenesis. To examine whether the codon72 polymorphism and IVS7+72C>T polymorphism of the human p53 gene are associated with spermatogenetic failure in Han-Chinese population. A case-control study was conducted with 198 idiopathic infertile patients with nonobstructive azoospermia or severe oligozoospermia and 233 fertile controls. We genotyped the two polymorphisms, codon72 and IVS7+72C>T, using polymerase chain reaction-restriction fragment length polymorphism assay. The polymorphisms were identified in both infertile patients and fertile controls. The allele and genotype frequencies of the two polymorphisms were not significantly different between the patients and controls. Further analysis showed that there was no statistically significant difference in the haplotype distributions between the patients and controls. The results of this study suggest that the codon72 and IVS7+72C>T polymorphisms of the p53 gene are unlikely to contribute to the pathogenesis of idiopathic male infertility with spermatogenetic failure.

A frequent Y chromosome b2/b3 subdeletion shows strong association with male infertility in Han-Chinese population.

BACKGROUND: Azoospermia factor c (AZFc) subdeletions were reported to be significant risk factors for spermatogenesis. In this study, we assessed the occurrence of classical AZF deletions and AZFc subdeletions and their impact on male infertility in a Han-Chinese population. METHODS: This study analysed a population of 699 subjects, including 451 idiopathic infertile patients with a range of fertility disorders and 248 fertile controls, using a retrospective design. Deletions were identified by multiplex PCR. RESULTS: The prevalence and phenotypes of the classical AZF deletions were similar to previous studies. Subdeletions of the AZFc region in patients showed similar overall frequencies in all sperm concentration categories of gr/gr (7.0%) and b2/b3 (8.9%). For controls, these subdeletions were also found with a prevalence of gr/gr (7.7%) and b2/b3 (3.2%). b1/b3 deletions were not found either in the patients or in the controls. CONCLUSION: Our data showed a higher frequency of deletion events in this Han-Chinese population than in populations elsewhere in the world. The classical AZF deletions were the primary genetic factors for spermatogenic failure, while no significant association was found for AZFc subdeletions with sperm concentration. However, the b2/b3 subdeletion was significantly associated with idiopathic male infertility (odds ratio, 2.93; 95% confidence interval 1.34-6.39) (P = 0.005), indicating a potential impairment of male fertility.