Environmental exposure during pregnancy and the risk of childhood allergic diseases.

BACKGROUND: Allergic diseases are one of the most common and important diseases that can exert hazardous effects on children's health. The prevalence of allergic diseases in childhood is gradually increasing all over the world in recent decades. Known causes of these diseases include anomalous immune responses and allergic inflammatory reactions, but the causes of allergic diseases in childhood are complex. DATA SOURCES: PubMed, Cochrane Library, Embase and Web of Science were searched for articles focusing on environmental exposure during pregnancy and the risk of childhood allergic diseases, including asthma and atopic dermatitis, and the possible underlying mechanism. RESULTS: In terms of environmental factors, allergic diseases in childhood are closely related to environmental chemical exposure during pregnancy, including bisphenols, phthalates acid esters, perfluorochemicals, polybrominated diphenyl ethers, and polychlorinated biphenyls. However, allergic diseases in childhood are also closely associated with maternal dietary nutrition, maternal intake of drugs, such as acetylsalicylic acid (aspirin), paracetamol and antibiotics, and maternal lifestyle. CONCLUSIONS: Several harmful environmental factors during pregnancy can result in the interruption of the function of helper T cells (Th1/Th2), cytokines and immunoglobulins and may activate allergic reactions, which can lead to allergic diseases during childhood.

Profiles of metabolic gene expression in the white adipose tissue, liver and hypothalamus in leptin knockout (LepΔI14/ΔI14 ) rats.

Leptin deficiency is principally linked to metabolic disorders. Leptin knockout (LepΔI14/ΔI14) Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of the white adipose tissue, liver and hypothalamus in LepΔI14/ΔI14 and wild-type (WT) rats. We found 1,651 differentially expressed (enriched) genes in white adipose tissue, 916 in the liver, and 306 in the hypothalamus in the LepΔI14/ΔI14 rats compared to WT. Gene ontology category and KEGG pathway analysis of the relationships among differentially expressed genes showed that these genes were represented in a variety of functional categories, including fatty acid metabolism, molecular transducers and cellular processes. The reliability of the data obtained from microarray was verified by quantitative real-time PCR on 14 representative genes. These data will contribute to a greater understanding of different metabolic disorders, such as obesity and diabetes.

The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine.

Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coli strain BL21 Star TM (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.

Associations of prenatal exposure to phenols with birth outcomes.

Many phenols are known to mimic or antagonize hormonal activities and may adversely affect fetal growth. A study of 567 pregnant women was conducted to investigate the relationship between prenatal phenol exposure and birth outcomes, including birth weight, length, and gestational age. We measured the concentrations of bisphenol A, benzophenone-3, 4-n-octylphenol and 4-n-nonylphenol in maternal urine and examine their association with birth outcomes. Categories of urinary benzophenone-3 concentration were associated with decreased gestational age in all infants (p for trend = 0.03). Between middle and low exposure groups, we also found bisphenol A was negatively associated with gestational duration (ßadjusted = -0.48 week; 95% confidence interval: -0.91, -0.05). After stratification by gender, we found the consistent results in infant boys with those in all infants, but we did not observe significant association for girls. In conclusion, we found prenatal phenol exposure was sex-specifically related to birth outcomes.

Preparation and immunogenicity of tag-free recombinant human eppin.

Human epididymal protease inhibitor (eppin) may be effective as a male contraceptive vaccine. In a number of studies, eppin with an engineered His(6)-tag has been produced using prokaryotic expression systems. For production of pharmaceutical-grade proteins for human use, however, the His(6)-tag must be removed. This study describes a method for producing recombinant human eppin without a His(6)-tag. We constructed plasmid pET28a (+)-His(6)-tobacco etch virus (TEV)-eppin for expression in Escherichia coli. After purification and refolding, the fusion protein His(6)-TEV-eppin was digested with TEV protease to remove the His(6)-tag and was further purified by NTA-Ni(2+) affinity chromatography. Using this procedure, 2 mg of eppin without a His(6)-tag was isolated from 1 l of culture with a purity of >95%. The immunogenicity of the eppin was characterized using male Balb/c mice.

BCL2 Ala43Thr is a functional variant associated with protection against azoospermia in a Han-Chinese population.

Apoptosis is very common during various stages of mammalian germ cell development and differentiation, and the BCL2 gene is one of the most important apoptotic regulators. Although its genetic variants are reported to be involved in cancers and autoimmune diseases, little information is available regarding BCL2 polymorphisms in male spermatogenesis. In the present study, single nucleotide polymorphisms (SNPs) in coding regions of the BCL2 gene were examined in a hospital-based, case-control study including 198 infertile patients with idiopathic azoospermia and 183 fertile controls. Subsequently, a functional study was conducted for comparison of paclitaxel-induced cytotoxicity and apoptosis between the BCL2 variant and the wild type in vitro. Three SNPs were found in exon 2--A21G (rs1801018), G127A (rs1800477), and C300T (rs61733416)--with the latter first reported in the Han-Chinese population. The frequency of G127A (GA+AA) genotype was significantly lower in azoospermic, infertile men compared to the age-matched controls (P = 0.01). This genotype may confer a lower risk of azoospermia (adjusted odd ratio [OR] = 0.448, 95% confidence interval = 0.226-0.889). In addition, HeLa cells expressing the BCL2 Ala43Thr (G127A), similar to the control cells, were more sensitive to paclitaxel-induced cytotoxicity and apoptosis than those expressing wild-type BCL2. Consistently, the cleaved PARP and p-BCL2 proteins were subsequently increased after paclitaxel treatment, as also predicted by the bioinformatics analysis. Considering the decreased antiapoptotic function of BCL2, these results suggest that the Ala43Thr variant is associated with protection against azoospermia in the Han-Chinese population.

[Ala499Val (C > T) and Lys939Gln (A > C) polymorphisms of the XPC gene: their correlation with male infertility].

OBJECTIVE: The Ala499Val (C > T) and Lys939Gln (A > C) of the XPC gene are two potentially functional nonsynonymous polymorphisms, which affect the rate of DNA repair and might change XPC production and activity. This study aimed to explore the distribution of these two polymorphisms in the Chinese Han population and their relationship with male infertility. METHODS: We genotyped the two polymorphisms of the XPC gene by the PCR-restriction fragment length polymorphism (PCR-RFLP) method in 318 infertile patients and 228 fertile male controls, detected the frequency of the alleles, and analyzed both the individual and the joint contribution of the two polymorphisms to male infertility. RESULTS: For the Ala499Val (C > T) polymorphism, the frequencies of the CC, CT, and TT genotypes were significantly different in distribution between the patients and the controls (P = 0.020). Males with the TT genotype had a lower risk of male infertility than those with the CC genotype (adjusted OR = 0.49, 95% CI: 0.23-0.88), and even lower than those with both CC and CT genotypes (adjusted OR = 0.39, 95% CI: 0.22-0.71). The Lys939Gln (A > C) polymorphism was not related with male infertility. The combined genotype analysis showed that the individuals with 1-4 risk alleles had a significantly higher risk of male infertility (adjusted OR = 2.75, 95% CI = 1.50-5.04) than those with 0 risk allele. CONCLUSION: The Ala499Val (C > T) polymorphism of the XPC gene is correlated with male infertility and may be a potential genetic risk factor for male infertility in the Chinese Han population.

Fenvalerate inhibits the growth of primary cultured rat preantral ovarian follicles.

Fenvalerate is a widely used synthetic pyrethroid insecticide and is reported to disrupt reproductive function in humans and animals. However, little is known about its influence on follicular development. In this study, rat preantral follicles were primary cultured to investigate the effects of fenvalerate on follicular survival rate, morphological change, steroid hormone levels and steroidogenesis related gene mRNA expression. Follicles were cultured with 0, 1, 5 and 25 micromol/L fenvalerate for 72 h. And then the morphous was assessed by conventional light microscopy, steroid hormones were measured by RIA, and the expressions of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc) were monitored by real-time quantitative PCR analysis. Results showed that fenvalerate inhibited the augmentation of follicular diameters but did not have detectable effects on follicular survival rates. The level of steroid hormones, such as progesterone, testosterone and estradiol, was inhibited. The inhibition might be due to the decreased expression levels of StAR and P450scc. These results suggested that fenvalerate restrained the follicular growth, and inhibited steroidogenesis by reducing StAR and P450scc gene expression, which might further contribute to the fenvalerate-induced reproductive dysfunction.

[An analysis on chromosome X, Y and 18 in the spermatozoa of asthenospermia patients by triple-color fluorescence in situ hybridization].

OBJECTIVE: To analyze the numerical aberration of chromosome X, Y and 18 in the spermatozoa of asthenospermia patients by triple-color fluorescence in situ hybridization. METHODS: The experiment included 10 asthenospermia patients and 5 healthy men with normal semen quality as controls. Fluorescence in situ hybridization (FISH) and probes for chromosomes including X, Y and 18 were used to determine the frequency of the aneuploid of the chromosomes in spermatozoa. RESULTS: Of the 45,547 spermatozoa counted from the semen samples, the hybridization rate was 99.18%. The frequencies of the chromosome disomies including XX18, XY18, YY18, X1818 and Y1818 were (0.124 +/- -0.086)%, (0.360 +/- 0.380)%, (0.109 +/- 0.195)%, (0.342 +/- 0.746)% and (0.299 +/- 0.564)% in the case group and (0.014 +/- 0.019)%, (0.090 +/- 0.080)%, (0.030 +/- 0.031)%, (0.068 +/- 0.103)% and (0.075 +/- 0.083)% in the control. The sperm aneuploid rate was 9.25% in the former and 2.70% in the latter, with significant difference in between (P< 0.01). CONCLUSION: Asthenospermia patients have a higher aneuploid rate of sperm chromosome than normal fertile men. However, larger samples are yet to be studied to obtain more scientific evidence.

Association of XRCC1 gene polymorphisms with idiopathic azoospermia in a Chinese population.

AIM: To assess the possible role of genetic polymorphisms in DNA repair gene XRCC1 (X-ray repair cross-complementing group 1) during spermatogenesis by investigating the associations of one promoter polymorphism (T-77C) and two exonic polymorphisms (Arg194Trp and Arg399Gln) in XRCC1 gene with risk of idiopathic azoospermia in a Chinese population. METHODS: The genotype and allele frequencies of three observed polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism based on a Chinese population consisting of 171 idiopathic azoospermia subjects and 247 normal-spermatogenesis controls. RESULTS: In our study, all the observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium. The 399A (GA+AA) allele frequency for idiopathic azoospermia subjects and controls was 0.216 and 0.269, respectively. Compared with GG genotype, the AA genotype of Arg399Gln showed a significant association with a decreased risk of idiopathic azoospermia (odds ratio = 0.315; 95% confidence interval = 0.12-0.86). However, no significant differences were found between the cases and controls for T-77C and Arg194Trp polymorphisms. The major haplotypes of XRCC1 gene were TCG, TTG and TCA, whereas no haplotypes appeared to be significantly associated with idiopathic azoospermia based on the cutoff of P < 0.05. CONCLUSION: In a selected Chinese population, AA genotype of Arg399Gln appears to contribute to a decreased risk of idiopathic azoospermia, while we have not any evidence of involvement of XRCC1 T-77C and Arg194Trp polymorphisms in idiopathic azoospermia.