Adriamycin induces H2AX phosphorylation in human spermatozoa

Aim： To investigate whether adriamycin induces DNA damage and the formation of γH2AX （the phosphorylated form of histone H2AX） foci in mature spermatozoa. Methods： Human spermatozoa were treated with adriamycin at different concentrations, γH2AX was analyzed by immunofluorescent staining and flow cytometry and doublestrand breaks （DSB） were detected by the comet assay. Results： The neutral comet assay revealed that the treatment with adriamycin at 2 μg/mL for different times （0.5, 2, 8 and 24 h）, or for 8 h at different concentrations （0,4, 2 and 10 μg/mL）, induced significant DSB in spermatozoa. Immunofluorent staining and flow cytometry showed that the expression of γH2AX was increased in a dose-dependent and time-dependant manner after the treatment of adriamycin. Adriamycin also induced the concurrent appearance of DNA maintenance/repair proteins RAD50 and 53BP 1 with γH2AX in spermatozoa. Wortmannin, an inhibitor of the phosphatidylinositol 3-kinase （PI3K） family, abolished the co-appearance of these two proteins with γH2AX. Conclusion： Human mature spermatozoa have the same response to DSB-induced H2AX phosphorylation and subsequent recruitment of DNA maintenance/ repair proteins as somatic cells.

The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis

The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.

Association between gestational anemia in different trimesters and neonatal outcomes:a retrospective longitudinal cohort study

Background Previous studies investigated the association between gestational anemia and neonatal outcomes.However,few studies explored whether the effects of gestational anemia could be eliminated by subsequent correction of anemia in the later stages of pregnancy.This study aimed to investigate the relationship between anemia in different trimesters and neonatal outcomes.Methods The study was conducted in Shanghai,China,with a sample of 46,578 pregnant women who delivered between January 1,2016 and July 1,2019.A multivariable logistic regression model was adopted to analyse the associations between maternal anemia and neonatal outcomes.Results The incidence of gestational anemia was 30.2%,including 4.4%in the first trimester,9.6%in the second trimester,and 16.2%in the third trimester.Only 24.5%(507/2066)of anemia that occurred in the first trimester and 29.6%(1320/4457)that occurred in the second trimester could be corrected in the later stages of pregnancy.Anemia occurring in the first trimester was associated with small for gestational age[odds ratio(OR)1.46;95%confidence interval(CI)1.20-1.78]and with fetal distress(OR 1.23;95%CI 1.08-1.40).Anemia corrected in the first trimester also was associated with a higher risk of small for gestational age.Conclusions Gestational anemia is a public health problem in China impacting neonatal health.Anemia in pregnancy could be corrected in only about a quarter of the women.Anemia in the first trimester,whether corrected or not,still led to lower birth weight;therefore,the prevention of anemia prior to pregnancy is important.

Long interpregnancy interval and adverse perinatal outcomes: a retrospective cohort study

We conducted a retrospective cohort study of 9,552 women experiencing their second delivery between 2014 and 2016 at the International Peace Maternity and Child Health Hospital to investigate the association between the interpregnancy interval(IPI)and adverse perinatal outcomes. With the 12–23-mon IPI as the reference category, logistic regression analyzes were used to examine associations between different IPIs(<12, 12–23, 24–59, 60–119, and ≥120 mon) and perinatal outcomes(gestational diabetes mellitus, premature membrane rupture, gestational hypertension, preterm birth, low birth weight, and macrosomia).Compared with the 12–23-mon IPI category, women with longer IPIs had a higher risk of adverse perinatal outcomes, and those with an IPI ≥120 mon had the highest risk of gestational diabetes mellitus and premature membrane rupture(adjusted odds ratio(OR) 1.76, 95% confidence interval(CI) 1.32–2.35 and adjusted OR 2.03, 95% CI 1.53–2.67, respectively). These results indicate that a longer IPI is associated with a higher risk of adverse perinatal outcomes and an IPI of ≥120 mon appears to be independently associated with a higher risk of gestational diabetes mellitus and premature membrane rupture.

Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis

Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree.In this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging.Genome-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis.The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature aging.Similarly,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive azoospermia.The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.