5-Aza-2'-deoxycytidine (AzC), trichostatin A (TSA), and its natural mimetic, sodium butyrate (NaB), are antineoplastic drugs that can modify the epigenetic status of donor cells prior to somatic cell nuclear transfer (SCNT). In this study, we used fibroblast cells treated with these drugs to investigate the direct and indirect effects of induced changes in DNA methylation and acetylation of the lysine 9 residue of histone H3 (H3K9). Additionally, we assayed cellular characteristics (cell growth, cell proliferation, cell cycle progression, and apoptosis) and SCNT efficiency in response to these drugs as well as monitoring these effects 24 h after removing the drugs. We observed the following: (1) AzC, TSA, and NaB all showed dose-dependent effects on different cellular characteristics; (2) TSA and NaB induced H3K9 hyperacetylation accompanied by DNA hypermethylation, whereas AzC induced DNA hypomethylation with no effect on H3K9 hyperacetylation; (3) TSA and NaB improved cloning efficiency, whereas AzC reduced it; and (4) unlike AzC, the effects of TSA and NaB on cellular characteristics and SCNT efficiency were reversed following drug removal. Our results indicate that somatic cells treated with TSA and NaB show better survival and recovery rates following the removal of these drugs. Moreover, H3K9 hyperacetylation (induced with TSA and NaB), but not DNA hypomethylation (induced with AzC), favors cloning efficiency.
A qualitative diagnosis of infertility requires attention to male and female physical abnormalities including endocrine anomalies and genetic conditions that interfere with reproduction. Many genes are likely to be involved in the complex process of reproduction. Congenital bilateral absence of the vas deferens (CBAVD) is a genital form of cystic fibrosis (CF) that is responsible for 2%-6% of male infertility. The incidence of CF varies in different populations; therefore, the incidence of CBAVD will also vary in different populations. The spectrum and distribution of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations differ between CBAVD and CF patients and are comparable to control individuals. Combinations of particular alleles at several polymorphic loci yield insufficient functional CFTR protein. CFTR mutations are also associated with congenital absence of the uterus and vagina (CAUV). Females with CF are found to be less fertile than normal healthy women. Because of techniques such as intracytoplasmic sperm injection (ICSI), CBAVD patients are now able to father children. Such couples, however, have an increased risk of having a child with cystic fibrosis, and therefore genetic testing and counseling should be provided. Around 10% of obstructive azoospermia is congenital and due to mutations in the CF gene. This review highlights the relationship of mutations in the CFTR gene with CBAVD and CAUV.
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