Neurotoxicity and Biomarkers of Lead Exposure: a Review

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies.Biomarkers are generally classified into three groups:biomarkers of exposure,effect,and susceptibility.The main body compartments that store lead are the blood,soft tissues,and bone;the half-life of lead in these tissues is measured in weeks for blood,months for soft tissues,and years for bone.Within the brain,lead-induced damage in the prefrontal cerebral cortex,hippocampus,and cerebellum can lead to a variety of neurological disorders,such as brain damage,mental retardation,behavioral problems,nerve damage,and possibly Alzheimer’s disease,Parkinson’s disease,and schizophrenia.This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Breast Milk Lead and Cadmium Levels in Suburban Areas of Nanjing,China

Objective To evaluate levels of lead(Pb) and cadmium(Cd) in the breast milk in the second postpartum month,to investigate the relationship between Pb/Cd levels in breast milk and some sociodemographic parameters,and to explore whether these levels affect the infants' physical status or the mothers' psychological status(postpartum depression).Methods A cross-sectional study was conducted between November 2009 and December 2010.Altogether 170 healthy mothers were enrolled from Nanjing Maternity and Child Health Care Hospital.The inclusion criteria were:voluntary to participate in this study,healthy,with no chronic disease,breastfeeding in the second postpartum month,living in a suburban but not non-industrial area of Nanjing,and not occupationally exposed to toxic metals.All the mothers completed a questionnaire and were evaluated based on the Edinburgh Postpartum Depression Scale(EPDS) to identify the risk of postpartum depression.Pb and Cd levels in breast milk were determined by inductively coupled plasma mass spectroscopy.The infants of these mothers were examined for their z scores of weight for age,length for age,head circumference for age,and body mass index for age.Results The median breast milk levels of Pb and Cd were 40.6 μg/L and 0.67 μg/L,respectively.In 164(96.5%) of the 170 samples,Pb levels were higher than the limit reported by the World Health Organization(> 5 μg/L).Breast milk Cd level was > 1 μg/L in 54(31.8%) mothers.The mothers with a history of anemia had a higher breast milk Pb level than those without a history of anemia(41.1 μg/L vs.37.9 μg/L,P = 0.050).The median breast milk Cd level in those who were active and passive smokers during pregnancy was significantly higher than that in non-smokers(0.88 μg/L vs.0.00 μg/L,P = 0.025).The breast milk Cd level in the mothers not taking iron and vitamin supplements for 2 months postpartum was higher than in those taking the supplements(iron supplement:0.74 μg/L vs.0.00 μg/L,P = 0.025;vitamin supplement:0.78 μg/L vs.0.00 μg/L,P = 0.005).Breast milk Cd level at the second postpartum month was negatively correlated with the z scores of head circumference(r = 0.248,P = 0.042) and weight for age at birth(r = 0.241,P = 0.024) in girls.No correlation was found between the breast milk Pb/Cd levels and the EPDS scores.Conclusion Considering the high levels of Pb and Cd in breast milk in this study,breast milk monitoring programs are necessary.

Blood Lead Levels During Pregnancy and Its Influencing Factors in Nanjing,China

Objective To investigate the blood lead levels （BLLs） in the duration of pregnancy and 6-12 weeks after delivery, and analyze the influencing factors of BLLs in healthy pregnant women. Methods Pregnant women were recruited from September 2009 to February 2010 at the prenatal clinic in Nanjing Maternity and Child Health Care Hospital. Altogether 174 healthy pregnant women without pregnant or obstetric complications or abnormal pregnancy outcomes were enrolled as the gravida group, and 120 healthy non-pregnant women as the control group. BLLs during pregnancy were determined by flame atomic absorption spectroscopy. Results BLLs in all the three pregnancy trimesters and postpartum were 59.8±24.3, 55.4±20.1, 55.9±19.7, and 67.6±17.4 μ/L, respectively, and the mean BLL in control group was 67.5±21.3 μg/L. BLLs during all the three trimesters were lower in the gravida group than in the control group （P=0.043, 0.021, and 0.028）. Furthermore, occupations, nutrients supplementation, and time of house/apartment painted were associated with BLLs in pregnant women. Lead-related occupations, cosmetics use, and living in a house painted less than 1 year before are risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors. Conclusion Supplementing calcium, iron, zinc, and milk, or avoiding contact with risk factors may help people, especially pregnant women, to reduce lead exposure.

Advances of Long Noncoding RNAs-mediated Regulation in Reproduction

Objective： Advances in genomics and molecular biology have led to the discovery of a large group of uncharacterized long noncoding RNAs （lncRNAs）. Emerging evidence indicated that many lncRNAs function in multiple biological processes and its dysregulation otten causes diseases. Recent studies suggested that almost all regulatory lncRNAs interact with biological macromolecules such as DNA, RNA, and protein. LncRNAs regulate gene expression mainly on three levels, including epigenetic modification, transcription, and posttranscription, through DNA methylation, histone modification, and chromatin remodeling. LncRNAs can also affect the development of diseases and tllerefore be used to diagnose and treat diseases. With new sequencing and microarray techniques, hundreds oflncRNAs involved in reproductive disorders have been identified, but their functions in these disorders are undefined. Data Sources： This review was based on articles published in PubMed databases up to July 10, 2017, with the tbllowing keywords： ＂long noncoding RNAs＂, ＂＇LncRNA＂, ＂placentation＂, and ＂＇reproductive diseases＂. Study Selection： Original articles and reviews on the topics were selected. Results： LncRNAs widely participate in various physiological and pathological processes as a new class of important regulatory/＇,actors. In spermatogenesis, spermatocytes divide and differentiate into mature spermatozoa. The whole process is elaborately regulated by the expression of phase-specific genes that involve many strains of lncRNAs. Literature showed that IncRNA in reproductive cumulus cells may contribute to the regulation of oocyte maturation, fertilization, and embryo development. Conclusions： LncRNA has been found to play a role in the development of reproduction. Meanwhile, we reviewed the studies on how lncRNAs participate in reproductive disorders, which provides a basis fbr the study of [ncRNA in reproduction regulation.

Endoplasmic reticulum stress-induced apoptosis in the development of reproduction

Proteins synthesized in the endoplasmic reticulum （ER） are properly folded with the assistance of ER chaperones. Accumulation of misfolded protein in the ER triggers an adaptive ER stress （ERS） response termed the unfolded protein response. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to reproductive response, including preimplantation embryos, testicular germ cell, placenta, and unexplained intrauterine growth restriction （IUGR）. The major ERS pathway constituents are present at all stages of preimplantation development and that the activation of ERS pathways can be induced at the 8-cell, morula and blastocyst stage. This review mainly introduced the research progress of ERS induced apoptosis of reproductive cells, providing a new direction for the research of reproductive disease therapy.

Role of Related Regulatory Long Noncoding RNAs on Mammalian Spermatogenesis

Long noncoding RNAs(lncRNAs)are transcribed by RNA molecules,which are longer than 200 nucleotides that lack an open reading frame of significant length and possess no obvious protein-coding capacity.Studies have shown that lncRNAs participate in many physiological processes such as gene imprinting and X chromosome inactivation.They regulate gene expression mainly through DNA methylation,histone modification,and chromatin remodeling.LncRNAs can also affect the development of diseases,and they can be useful to diagnose and treat diseases.With the development of new sequencing and microarray techniques,hundreds of lncRNAs involved in spermatogenesis have been identified,but their functions in the testis are undefined.Herein,we will discuss the biology and regulation of lncRNAs,as well as the bioinformatics tools and searchable databases used to study them in the testis.We hope that this information will provide new insights in treating male reproductive diseases.

Evaluation of circulating tumor DNA as a biomarker for gynecological tumors

Circulating tumor DNA(ctDNA)is a DNA fragment released into the peripheral blood by apoptotic or necrotic tumor cells,which carry the basic genetic information after gene mutation.The detection and analysis of ctDNA can provide genomic information on the size and development of tumor;therefore,it is considered as an emerging and promising tumor biomarker for cancer progression,reoccurrence,and routine monitoring after surgery.Albeit the isolation method is relatively simple due to the stability of ctDNA,the abundance of ctDNA is extremely low,and result from the high content of background cell free DNA(cfDNA),the large difference between individuals,and the need of predicted detection sites,it is necessary to analyze ctDNA in a comprehensive way.At present,the main methods that meet the needs of ctDNA detection with sensitivity and specificity are amplification refractory mutation system PCR(ARMS-PCR),digital-PCR(dPCR)and high-throughput sequencing.Among them,dPCR has advantages in practicality,which can realize absolute quantification of single-molecule DNA,detect and trace DNA molecules and conduct quantitative analysis,providing a reliable basis for clinical monitoring of tumor recurrence and minimal residual diseases.The study reviews the detection and potential value of ctDNA in gynecologic tumors.

The Influence of Sperm DNA Damage and Semen Homocysteine on Male Infertility

Background:To explore the relationship of sperm DNA fragmentation index(DFI),serum and seminal plasma homocysteine(Hcy),and semen parameters in patients with severe spermatogenetic dysfunction.Methods:A total of 77 infertile males treated in our hospital for severe spermatogenetic dysfunction from January 2016 to November 2017 were recruited.The involved patients were divided into two groups:oligozoospermia(SOM group,35 cases)and asthenozoospermia(OAT group,42 cases).The control group(NM group)contained 31 healthy males without reproductive dysfunctions.All the participants involved were tested in the items below:spermatozoa parameters,spermatozoa DFI,serum Hcy level and seminal plasma Hcy level,concentration of seminal plasma malondialdehyde(MDA),and total antioxidant capacity(TAC).Results:Between the SOM group and NM group,there were significantly difference in sperm concentration,motility and vitality,concentration of MDA,and TAC.The spermatozoa DFI and Hcy levels in SOM group were significantly higher than those of the NM group.Sperm DFI was positively correlated with serum Hcy level(r=0.083,P<0.05).Serum Hcy level was negatively correlated with sperm concentration(r=−0.186,P<0.05)and sperm vitality(r=−0.216,P<0.05).The serum Hcy level was not correlated with sperm Hcy level(r=0.103,P>0.05).Conclusions:The elevated Hcy level and spermatozoa DFI may be important factors of the severe spermatogenetic dysfunction,which can be used as semen index to evaluate sperm quality and male fertility.