CHFR is important for the survival of male premeiotic germ cells

Lu, Lin-Yu; Yu, Xiaochun

doi:10.1080/15384101.2015.1093701

Cited by 6 publications

(3 citation statements)

References 23 publications

(33 reference statements)

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“…Some authors have shown in animal models that the spermatocyte can actuate various DSB repair mechanisms ( 36 ) through non-homologous end-joining (NHEJ) and homologous recombination (HR) ( 35 , 36 ). These two mechanisms may co-exist ( 36 – 38 ) but if inadequate, can introduce new mutations. Despite all this, sperm with fragmented DNA can be fertile, and the biological impact of an abnormal sperm chromatin structure depends on the combined effects of the extent of DNA or chromatin damage in the sperm and the capacity of the oocyte to repair that damage ( 35 , 39 – 42 ).…”

Section: Introductionmentioning

confidence: 99%

Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

et al. 2018

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Testicular cancer (TC) is one of the most treatable of all malignancies and the management of the quality of life of these patients is increasingly important, especially with regard to their sexuality and fertility. Survivors must overcome anxiety and fears about reduced fertility and possible pregnancy-related risks as well as health effects in offspring. There is thus a growing awareness of the need for reproductive counseling of cancer survivors. Studies found a high level of sperm DNA damage in TC patients in comparison with healthy, fertile controls, but no significant difference between these patients and infertile patients. Sperm DNA alterations due to cancer treatment persist from 2 to 5 years after the end of the treatment and may be influenced by both the type of therapy and the stage of the disease. Population studies reported a slightly reduced overall fertility of TC survivors and a more frequent use of ART than the general population, with a success rate of around 50%. Paternity after a diagnosis of cancer is an important issue and reproductive potential is becoming a major quality of life factor. Sperm chromatin instability associated with genome instability is the most important reproductive side effect related to the malignancy or its treatment. Studies investigating the magnitude of this damage could have a considerable translational importance in the management of cancer patients, as they could identify the time needed for the germ cell line to repair nuclear damage and thus produce gametes with a reduced risk for the offspring.

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Section: Introductionmentioning

confidence: 99%

Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

et al. 2018

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“…The upstream regulators genes of candidate DcoExp modules, harboring functional candidate variants, were follows: DLG1 (Tan HF), AGER (Saddlebrown HF), SORT1 (Saddlebrown HF), HNRNPAB (Saddlebrown HF), TBX6 (Red HF), HSF1 (Purple HF and Darkgreen HF), LEPR (Lightgreen HF), DYSF (Lightgreen HF), BCKDK (Lightgreen HF), CHFR (Grey60 HF), ERN2 (Green HF), and RDH10 (Darkgreen HF). Among these genes, it was possible to identify relevant biological processes associated with fertility, such as oocyte polarization during maturation (DLG1), disorders of the müllerian ducts (TBX6), regulation of affects gonads or gonadotrophs (LEPR), and reproductive success (HSF1) [57][58][59][60][61][62].…”

Section: Differentially Co-expressed Modules and The Identification Of Functional Candidate Genesmentioning

confidence: 99%

Weighted Gene Correlation Network Meta-Analysis Reveals Functional Candidate Genes Associated with High- and Sub-Fertile Reproductive Performance in Beef Cattle

Fonseca

Suárez-Vega

Cánovas

2020

Genes

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Improved reproductive efficiency could lead to economic benefits for the beef industry, once the intensive selection pressure has led to a decreased fertility. However, several factors limit our understanding of fertility traits, including genetic differences between populations and statistical limitations. In the present study, the RNA-sequencing data from uterine samples of high-fertile (HF) and sub-fertile (SF) animals was integrated using co-expression network meta-analysis, weighted gene correlation network analysis, identification of upstream regulators, variant calling, and network topology approaches. Using this pipeline, top hub-genes harboring fixed variants (HF × SF) were identified in differentially co-expressed gene modules (DcoExp). The functional prioritization analysis identified the genes with highest potential to be key-regulators of the DcoExp modules between HF and SF animals. Consequently, 32 functional candidate genes (10 upstream regulators and 22 top hub-genes of DcoExp modules) were identified. These genes were associated with the regulation of relevant biological processes for fertility, such as embryonic development, germ cell proliferation, and ovarian hormone regulation. Additionally, 100 candidate variants (single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs)) were identified within those genes. In the long-term, the results obtained here may help to reduce the frequency of subfertility in beef herds, reducing the associated economic losses caused by this condition.

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“…Specifically DNA synthesis with proper fidelity is essential for repair of programmed DNA double strand breaks (DSBs) that are essential for chromosome dynamics in meiotic prophase I. Meiotic DSBs are repaired through two pathways, a synthesis-dependent strand annealing (SDSA) pathway to form non-crossover products and the classical pathway through double Holiday Junction (dHJ) formation to create both crossover and non-crossover products (Fishel, 2015;Lu and Yu, 2015). The DSBs that persist till pachynema are more likely to be repaired through the classical pathway to generate crossovers (Allers and Lichten, 2001).…”

Section: Introductionmentioning

confidence: 99%

Role of HP1β during spermatogenesis and DNA replication

et al. 2020

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Maintaining genomic stability in a continually dividing cell population requires accurate DNA repair, especially in male germ cells. Repair and replication protein access to DNA, however, is complicated by chromatin compaction. The HP1β chromatin protein, encoded by Cbx1, is associated with chromatin condensation but its role in meiosis is not clear. To investigate the role of Cbx1 in male germ cells, we generated testis specific Cbx1 deficient transgenic mice by crossing Cbx1 flox/flox (Cbx1 f/f ) mice with Stra8 Cre +/mice. Loss of Cbx1 in testes adversely affected sperm maturation and Cbx1 deletion increased seminiferous tubule degeneration and basal level DNA damage., We observed that Cbx1 -/-MEF cells displayed reduced resolution of stalled DNA replication forks as well as decreased fork restart, indicating defective DNA synthesis. Taken together, these results suggest that loss of Cbx1 in growing cells leads to DNA replication defects and associated DNA damage that impact cell survival..

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CHFR is important for the survival of male premeiotic germ cells

Cited by 6 publications

References 23 publications

Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

Weighted Gene Correlation Network Meta-Analysis Reveals Functional Candidate Genes Associated with High- and Sub-Fertile Reproductive Performance in Beef Cattle

Role of HP1β during spermatogenesis and DNA replication

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