Titanium dioxide nanoparticles (TiO2 NPs) were used worldwide for decades, and pregnant women are unable to avoid exposing to them. Studies revealed that TiO2 NPs could kill many kinds of bacteria, but whether they would affect the composition of gut microbiota, especially during pregnancy, was seldom reported. And, what adverse effects may be brought to pregnant females was also unknown. In this study, we established the prenatal exposure model of rats to explore the effects of TiO2 NPs on gut microbiota. We observed an increasing trend, but not a significant change of alpha-diversity among control and exposure groups at gestation day (GD) 10 and GD 17 during normal pregnancy process. Each different time point had unique gut microbiota operational taxonomic units (OTUs) characteristics. The abundance of Ellin6075 decreased at GD 10 and GD 17, Clostridiales increased at GD 10, and Dehalobacteriaceae decreased at GD 17 after TiO2 NPs exposure. Further phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) prediction indicated that the type 2 diabetes mellitus related genes were enhanced, and taurine metabolism was weakened at the second-trimester. Further study showed that the rats’ fasting blood glucose levels significantly increased at GD 10 (P < 0.05) and GD 17 (P < 0.01) after exposure. Our study pointed out that TiO2 NPs induced the alteration of gut microbiota during pregnancy and increased the fasting blood glucose of pregnant rats, which might increase the potential risk of gestational diabetes of pregnant women.

Congenital limb malformations (CLMs) affect 1 in 500 live births. However, the value of exome sequencing (ES) for CLM is lacking. The purpose of this study was to decipher the mutational signature of CLM on an exome level. We enrolled a cohort of 66 unrelated probands (including 47 families) with CLM requiring surgical correction. ES was performed for all patients and available parental samples. A definite molecular diagnosis was achieved in 21 out of 66 (32%) patients. We identified 19 pathogenic or likely pathogenic single-nucleotide variants and three copy number variants, of which 11 variants were novel. We identified four variants of uncertain significance. Additionally, we identified RPL9 and UBA2 as novel candidate genes for CLM. By comparing the detailed phenotypic features, we expand the phenotypic spectrum of diastrophic dysplasia and chromosome 6q terminal deletion syndrome. We also found that the diagnostic rate was significantly higher in patients with a family history of CLM (p = 0.012) or more than one limb affected (p = 0.034). Our study expands our understanding of the mutational and phenotypic spectrum of CLM and provides novel insights into the genetic basis of these syndromes.

Anti-Müller hormone (AMH) plays an important role in reproductive development and has a wide potential clinical application value. Phthalates have been widely found in human living environment and have negative effects on human reproduction. This study aimed to explore the relationship between urinary phthalate metabolites and serum AMH level in the general male population. Cross-sectional analyses were performed with a population of 489 men aged more than 12 years who participated in National Health and Nutrition Examination Survey (NHANES) 2003–2004 by Centers for Disease Control and Prevention, the United States. NHANES public data (demographic and socioeconomic information, examinations, and laboratory tests) were analyzed using Kruskal-Wallis test, Wilcoxon test and multivariable regression. Results showed that the urine concentration of mono (3-carboxypropyl) phthalate (MCPP) of 12–20 age group was significantly positively correlated with serum AMH concentration in the model without any covariates (p < 0.05). In the 60-year-old group, the monomethyl phthalate (MEP), mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations were significantly correlated with serum AMH concentrations in models both with and without covariates (all p < 0.05). It could be concluded that exposure to phthalates might have negative effects on AMH level, especially in seniors. AMH could be used as a marker of exposure to phthalates in aged males. How exposure to phthalates affected AMH level and what the potential long-term health consequences of their relationship are needs more investigation.

Endogenous expression level of Gas1 in six colon cancer cells demonstrated by Western blot (A) and RT-PCR (B).