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Abstract: The chemotherapeutic agents used to treat non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), have adverse effects on male reproductive function and progeny outcome. To determine the reversibility of these effects, male rats received a CHOP treatment mimicking human exposure. CHOP reduced testicular and epididymal weights; these remained decreased after 9 weeks recovery. This treatment also decreased testicular sperm number and increased spermatozoal DNA damage. Although sperm production returned to control values after 9 weeks recovery, DNA damage persisted. Decreased litter size, and increased pre- and post-implantation losses were observed among litters sired by CHOP-exposed males. Litter size and pre-implantation loss returned to control within 3 weeks post-treatment and post-implantation loss by 6 weeks. Thus, effects of CHOP on progeny outcome were reversed 9 weeks post-treatment, although germ cell DNA breaks remained elevated. These data suggest that the ability to sire viable progeny may not be a sensitive measure of spermatozoal quality in rats. [Copyright &y& Elsevier]

Background: The aim of the present study was to investigate the association of fMRI blood oxygen--level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD). Methods: We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyro-sequencing. Results: Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation. Limitations: It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn. Conclusion: Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery. [ABSTRACT FROM AUTHOR]

Serotonin plays an important role in the etiology of depression. Serotonin is also crucial for brain development. For instance, animal studies have demonstrated that early disruptions in the serotonin system affect brain development and emotion regulation in later life. A plausible explanation is that environmental stressors reprogram the serotonin system through epigenetic processes by altering serotonin system gene expression. This in turn may affect brain development, including the hippocampus, a region with dense serotonergic innervations and important in stress-regulation. The aim of this study was to test whether greater DNA methylation in specific CpG sites at the serotonin transporter promoter in peripheral cells is associated with childhood trauma, depression, and smaller hippocampal volume. We were particularly interested in those CpG sites whose state of methylation in peripheral cells had previously been associated with in vivo measures of brain serotonin synthesis. Thirty-three adults with Major Depressive Disorder (MDD) (23 females) and 36 matched healthy controls (21 females) were included in the study. Depressive symptoms, childhood trauma, and high-resolution structural MRI for hippocampal volume were assessed. Site-specific serotonin transporter methylation was assessed using pyrosequencing. Childhood trauma, being male, and smaller hippocampal volume were independently associated with greater peripheral serotonin transporter methylation. Greater serotonin transporter methylation in the depressed group was observed only in SSRI-treated patients. These results suggest that serotonin transporter methylation may be involved in physiological gene-environment interaction in the development of stress-related brain alterations. The results provide some indications that site-specific serotonin transporter methylation may be a biomarker for serotonin-associated stress-related psychopathology. [ABSTRACT FROM AUTHOR]

Highlights: [•] A clonal-based HIV-1 tropism phenotypic assay was developed. [•] Env-pseudotyped viruses were produced by co-transfection of the env-pcDNA3.1/V5HisTOPO expression vector and a backbone pNL4-3.Luc.E-R- in 293T cell cultures. [•] Coreceptor use was tested by infection of U87-CD4-CCR5+ and U87-CD4-CXCR4+ cells. [•] This sensitive clonal based phenotypic assay was able to differentiate between the truly dual-tropic viruses and a mixture of R5- and X4-tropic viruses. [•] Minor variants were always detectable when present at 0.4% or greater in the mixtures. [ABSTRACT FROM AUTHOR]