Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Omoto Y
PROVIDER: S-EPMC549492 | biostudies-other | 2005 Feb
REPOSITORIES: biostudies-other
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Project description:OBJECTIVE:Ovarian carcinoma (OC) is rare in young women and the fraction of early onset OC attributable to inherited mutations in known OC genes is uncertain. We sought to characterize the fraction of OC that is heritable in women diagnosed with ovarian, fallopian tube, or peritoneal carcinoma at forty years of age or younger. METHODS:We sequenced germline DNA from forty-seven women diagnosed with OC at age 40 or younger ascertained through a gynecologic oncology tissue bank or referred from outside providers using BROCA, a targeted capture and massively parallel sequencing platform that can detect all mutation classes. We evaluated 11 genes associated with ovarian carcinoma (BARD1, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51D, and RAD51C) and additional candidate genes in DNA repair (ATM, BAP1, CHEK2, MRE11A, NBN, PTEN, TP53). We counted only clearly damaging mutations. RESULTS:Damaging mutations in OC genes were identified in 13 of 47 (28%) subjects, of which 10 (77%) occurred in BRCA1 and one each occurred in BRCA2, MSH2, and RAD51D. Women with a strong family history were no more likely to have an OC gene mutation (8/17, 47%) than those without a strong family history (9/30, 30%, P=0.35). Additionally, damaging mutations in non-OC genes were identified, one in NBN and one in CHEK2. CONCLUSIONS:A high proportion of young women with invasive OC have mutations in BRCA1, and a smaller fraction have mutations in other known OC genes. Family history was not associated with mutation status in these early onset cases.
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Project description:In humans and model species, alterations of sperm DNA methylation patterns have been reported in cases of spermatogenesis defects, male infertility and exposure to toxins or nutritional challenges, suggesting that a memory of environmental or physiological changes is recorded in the sperm methylome. The objective of this study was to ascertain if early life plane of nutrition could have a latent effect on DNA methylation patterns in sperm produced post-puberty. Holstein-Friesian calves were assigned to either a high (H) or moderate (M) plane of nutrition for the first 24 weeks of age, then reassigned to the M diet until puberty, resulting in HM and MM groups. Sperm DNA methylation patterns from contrasted subgroups of bulls in the HM (ejaculates recovered at 15 months of age; n = 9) and in the MM (15 and 16 months of age; n = 7 and 9, respectively) were obtained using Reduced Representation Bisulfite Sequencing. Both 15 and 16 months were selected in the MM treatment as these bulls reached puberty approximately 1 month after the HM bulls. Hierarchical clustering demonstrated that inter-individual variability unrelated to diet or age dominated DNA methylation profiles. While the comparison between 15 and 16 months of age revealed almost no change, 580 differentially methylated CpGs (DMCs) were identified between the HM and MM groups. Differentially methylated CpGs were mostly hypermethylated in the HM group, and enriched in endogenous retrotransposons, introns, intergenic regions, and shores and shelves of CpG islands. Furthermore, genes involved in spermatogenesis, Sertoli cell function, and the hypothalamic-pituitary-gonadal axis were targeted by differential methylation when HM and MM groups were compared at 15 months of age, reflecting the earlier timing of puberty onset in the HM bulls. In contrast, the genes still differentially methylated in MM bulls at 16 months of age were enriched for ATP-binding molecular function, suggesting that changes to the sperm methylome could persist even after the HM and MM bulls reached a similar level of sexual maturity. Together, results demonstrate that enhanced plane of nutrition in pre-pubertal calves associated with advanced puberty induced modest but persistent changes in sperm DNA methylation profiles after puberty.
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Project description:Puberty is a special transition period in sexual maturation, and it has been extensively studied in vertebrates in the past decades. In mammals, the initiation of puberty involves activation of numerous genes; however, there have been few comprehensive reports in small model teleosts such as the zebrafish. In the zebrafish, the onset of puberty in females is marked by the appearance of the first wave of pre-vitellogenic (PV) follicles in the ovary during sexual maturation. Using transcriptomics and real-time qPCR, this study was undertaken to investigate temporal gene expression differences between the primary growth (PG) follicles and pre-vitellogenic (PV) follicles, with particular emphasis on oocyte and follicular cell specific genes as well as several closely associated signaling pathways. Our results showed that totally 1082 genes were significantly upregulated and 530 evidently downregulated during the PG-PV transition, and among them were some well recognized biomarkers such as cyp19a1a, fshr, inha and inhbaa and some novel genes like notch3, amh, gadd45ga and lpl. Further gene ontology analysis showed that egg coat formation and steroid hormone mediated signaling pathway might be critical for follicle activation from PG to PV stage. In addition, KEGG identified several signaling pathways that might play pivotal roles in early folliculogenesis, including phosphatidylinositol signaling system, glycolsaminoglycan biosynthesis, RNA transport, and p53 signaling pathways. Overall, this study reported a comprehensive analysis for biomarker genes and potential pathways involved in PG-PV transition or follicle activation, which also marks female puberty onset in the zebrafish when occurring for the first time in sexual maturation.
2018-10-01 | GSE99308 | GEO