BackgroundThe mismatch repair (MMR) pathway plays an important role in the maintenance of the genome integrity, meiotic recombination and gametogenesis. This study investigated whether genetic variations in MMR genes are associated with an increased risk of sperm DNA damage and male infertility.MethodsWe selected and genotyped 21 tagging single nucleotide polymorphisms (SNPs) in five MMR genes (MLH1, MLH3, PMS2, MSH4 and MSH5) using the SNPstream 12-plex platform in a case-control study of 1,292 idiopathic infertility patients and 480 fertile controls in a Chinese population. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay in 450 cases. Fluorescence resonance energy transfer (FRET) and co-immunoprecipitation techniques were employed to determine the effects of functional variants.ResultsOne intronic SNP in MLH1 (rs4647269) and two non-synonymous SNPs in PMS2 (rs1059060, Ser775Asn) and MSH5 (rs2075789, Pro29Ser) seem to be risk factors for the development of azoospermia or oligozoospermia. Meanwhile, we also identified a possible contribution of PMS2 rs1059060 to the risk of male infertility with normal sperm count. Among patients with normal sperm count, MLH1 rs4647269 and PMS2 rs1059060 were associated with increased sperm DNA damage. Functional analysis revealed that the PMS2 rs1059060 can affect the interactions between MLH1 and PMS2.ConclusionsOur results provide evidence supporting the involvement of genetic polymorphisms in MMR genes in the aetiology of male infertility.

No abstract

The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity. Both proteins have been functionally linked to germ cell apoptosis, which may affect human infertility, but very little is known on how common polymorphisms in these genes may influence germ cell apoptosis and the risk of male infertility. Thus, this study was designed to test whether three previously described polymorphisms 72Arg>Pro (rs1042522) and the Ex2+19C>T (rs2287498) in TP53, and the 5' untranslated region (5' UTR) 309T>G (rs937283) in MDM2, are associated with idiopathic male infertility in a Chinese population. The three polymorphisms were genotyped using OpenArray assay in a hospital-based case-control study, including 580 infertile patients and 580 fertile controls. Our analyses revealed that TP53 Ex2+19C>T and MDM2 309T>G polymorphisms are associated with male infertility. Furthermore, we detected a nearly statistically significant additive interaction between TP53 rs2287498 and MDM2 rs937283 for the development of male infertility (P(interaction)=0.055). In summary, this study found preliminary evidence, demonstrating that genetic variants in genes of the TP53 pathway are risk factors for male infertility.

To evaluate the association with genetic polymorphisms in Xeroderma pigmentosum complementation group D (XPD) gene of esophageal squamous cell carcinoma (ESCC) risk in a population of Yili Prefecture, in Xinjiang, China. A hospital-based case-control study was designed with 571 samples including 213 ESCC patients and 358 controls with age, gender and ethnicity-matched subjects (Kazakh, Uygur and Han ethnic). Genotypes were determined by PCR restriction fragment length polymorphism (PCR-RLFP) and confirmed by sequence. Relative risk associated with a particular genotype was estimated by calculating odds ratios (OR) along with 95% confidence intervals (CI). Significant ESCC risk was observed for XPD Lys751Gln (rs13181) frequency of presence C allele (OR: 1.409, 95% CI: 1.005-1.976) in the three ethnics. XPD Asp312Asn (rs1799793) of Han ethnic was associated with a borderline decrease of ESCC (OR: 0.362, 95% CI: 0.145-0.906), however, it was associated with ESCC risk in Uygur ethnic (OR: 2.403, 95% CI: 1.087-5.310). The results demonstrated an association between the XPD Lys751Gln (rs13181) for frequency of presence C allele and risk for ESCC in the three ethnics of Yili Prefecture, in Xinjiang, China. XPD Asp312Asn (rs1799793), which was associated with a borderline decrease of Han ethnic and risk of Uygur ethnic of ESCC, may play a different role in the three ethnics of ESCC.

Bactrocera minax, one of the most devastating citrus pests in Asia, has two developmental stages (mature larva and pupa) that complete their life cycle in the soil. Currently, southern China has a climate with abundant autumn rains, and soil moisture can be a major factor affecting the survival of larvae and pupae of B. minax. In the present study, we evaluated the effects of water immersion and high soil moisture content on the development of mature larvae and pupae of B. minax. When immersed in water for 1 d, 100% of mature larvae of B. minax were knocked out. When larvae were immersed for less than 6 d, however, more than 92% of knocked-out larvae recovered within 24 h. The days of water immersion with 50% and 90% recovery ratios (indicated as RD50 and RD90) were 10.3 d and 6.4 d, respectively. When larvae were immersed less than 6 d, the mortality ratios of larvae were not significantly different from those that were not immersed at all. The days of immersion causing 50% and 90% mortality of larvae (MD50 and MD90, respectively) were 7.6 d and 11.1 d, respectively. The pupation ratios of larvae were also observed to be not significantly different compared to non-immersion, and the days of immersion causing 50% and 90% pupation (PD50 and PD90, respectively) were 6.6 d and 0.8 d, respectively. Larval respiration rates were reduced after water immersion as a strategy for larval survival. High water content was not detrimental to pupae of B. minax. Adult emergence did not significantly decrease in soil with high water content, even though pupae were under those conditions for 161–175 d. The respiration rates of pupae were lower in soil with different moisture levels and were not significantly different, which ensured the survival of pupae in high water content. Reduced respiration rate is a strategy for survival of larvae and pupae, and remarkable tolerance to high moisture conditions could explain the high rate of spread and geographical distribution of B. minax. The results of this study provide a reference for the occurrence and control of B. minax.