An Essential Role for Functional Telomeres in Mouse Germ Cells during Fertilization and Early Development

Lin, Liu; Blasco, Marı́a A.; Trimarchi, James R.; Keefe, David L.

doi:10.1006/dbio.2002.0735

Cited by 150 publications

(121 citation statements)

References 56 publications

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“…Telomeres are first structures to respond to oocyte signals for male pronucleus development at fertilization and microtubule guided movement [11]. Shortened telomeres in germ cells result in defects in early cleavage and preimplantation and this also has been documented in telomerase knockout mouse [9]. Telomere mediate nuclear reorganization leads to pairing and recombination of homologous chromosomes during meiosis and shortened telomeres result in meiotic arrest or aneuploidy and abnormal embryonic development and decreased rate of blastocyte development [46].…”

Section: Discussionmentioning

confidence: 99%

“…Telomere mediate nuclear reorganization leads to pairing and recombination of homologous chromosomes during meiosis and shortened telomeres result in meiotic arrest or aneuploidy and abnormal embryonic development and decreased rate of blastocyte development [46]. Telomerase knockout mouse exhibit decreases fertility, reduced litter size in subsequent generations and eventual sterility [9]. Hetrogenetiy of mouse and human somatic cell telomere length is also seen in oocytes [47].…”

Section: Discussionmentioning

confidence: 99%

“…Though shortened telomere length plays a significant role in various diseases its role in iRPL has not been evaluated. Chromosomes having sufficient telomere length have probable role in fertilization and shortened telomeres either from sperm or oocyte may contribute to abnormal cleavage and impaired development, as demonstrated in knock-out mice [9].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Thilagavathi

Mishra

Kumar

et al. 2013

J Assist Reprod Genet

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Purpose Telomere length plays a significant role in various disorders; however, its role in idiopathic recurrent pregnancy loss (iRPL) is not known. The objective of this study was to assess telomere length in peripheral blood leukocytes in couples experiencing unexplained recurrent pregnancy loss (iRPL). Methods The study included 25 couples experiencing iRPL and 20 controls. The mean relative telomere length was measured by quantitative Real Time PCR (Q-PCR) based assay, which measures the average ratio of telomere repeat copy number to a single copy gene (36B4) copy number (T/S ratio) in each sample. Results The relative leukocyte mean telomere length (T/S) in both men and women from iRPL group was significantly lower (p<0.05) when compared to controls. A significant (P<0.05) negative correlation was found between age and leukocyte telomere length (T/S ratio). Among the sperm parameters seminal volume was found to be negatively (r = −0.4679) associated with the telomere T/S ratio. The DNA fragmentation index of sperm showed positive correlation (r=0.4744) with telomere length. In this preliminary study, we found that shorter telomere length in both men and women may be associated with early pregnancy loss. Conclusion In conclusion, shorter telomere length in both male and female partners appears to play a role in the idiopathic recurrent pregnancy loss. Loss of telomeric DNA due to oxidative stress needs further analysis. Analysis of telomere length in germ cells are needed to further substantiate the findings of this study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Thilagavathi

Mishra

Kumar

et al. 2013

J Assist Reprod Genet

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“…Female mice were induced to super-ovulate by consecutive injection of pregnant mare's serum gonadotropin and human chorionic gonadotropin and mated with proven fertile males. Zygotes were collected from oviducts 20 -21 h after injection of human chorionic gonadotropin and cultured at 37°C in a humidified atmosphere of 7% CO 2 in potassium simplex optimized media supplemented with nonessential amino acids (42).…”

Section: Methodsmentioning

confidence: 99%

“…Cell Survival-To further confirm that arsenic-induced oxidative stress and increased apoptosis resulted from telomere dysfunction, we compared embryo survival after exposure to arsenic treatment between wild-type (WT) and age-matched, third generation telomerase-deficient mice (G3 TR Ϫ/Ϫ ) with shortened telomeres (36,37,42). Young G3 TR Ϫ/Ϫ mice were chosen because cells from these mice show no chromosome fusions with relatively shortened telomeres compared with wild-type cells (40,44).…”

Section: Telomerase-deficient Mouse Embryos With Shortened Telomeres mentioning

confidence: 99%

Oxidative Stress Contributes to Arsenic-induced Telomere Attrition, Chromosome Instability, and Apoptosis

Liu

Trimarchi

Navarro

et al. 2003

Journal of Biological Chemistry

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196

141

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The environmental contaminant arsenic causes cancer, developmental retardation, and other degenerative diseases and, thus, is a serious health concern worldwide. Paradoxically, arsenic also may serve as an antitumor therapy, although the mechanisms of its antineoplastic effects remain unclear. Arsenic exerts its toxicity in part by generating reactive oxygen species. We show that arsenic-induced oxidative stress promotes telomere attrition, chromosome end-to-end fusions, and apoptotic cell death. An antioxidant, N-acetylcysteine, effectively prevents arsenic-induced oxidative stress, telomere erosion, chromosome instability, and apoptosis, suggesting that increasing the intracellular antioxidant level may have preventive or therapeutic effects in arsenic-induced chromosome instability and genotoxicity. Embryos with shortened telomeres from late generation telomerase-deficient mice exhibit increased sensitivity to arsenic-induced oxidative damage, suggesting that telomere attrition mediates arsenic-induced apoptosis. Unexpectedly, arsenite did not cause chromosome endto-end fusions in telomerase RNA knockout mouse embryos despite progressively damaged telomeres and disrupting embryo viability. Together, these findings may explain why arsenic can initiate oxidative stress and telomere erosion, leading to apoptosis and anti-tumor therapy on the one hand and chromosome instability and carcinogenesis on the other.Arsenic is a significant environmental concern worldwide because millions of people are at risk of drinking water contaminated by arsenic (1, 2). Epidemiological data show that chronic exposure of humans to inorganic arsenic is associated with hepatic injury, peripheral neuropathy, and increased rates of a wide variety of cancers, particularly of the skin, lung, bladder, and liver (3-5). Arsenic also produces toxic effects on the female reproductive system, including ovarian dysfunction (6), aberrant embryo development and lethality (7,8), and postnatal growth retardation (9). Interestingly, it also has proven useful for anti-cancer therapy (10 -12), although the mechanisms underlying its paradoxical (antineoplastic) effects remain unclear.Many possible modes of arsenic action have been proposed, including chromosomal abnormalities, oxidative stress, altered DNA repair and DNA methylation patterns, altered cell proliferation, abnormal gene amplification, and inhibition of p53 and telomerase (5, 13-18). In particular, arsenic exerts its toxicity by generating reactive oxygen species (ROS) 1 (19 -22). Mitochondria, the main source of ROS production, which also play a crucial role in the control of apoptosis (23, 24), have been implicated in arsenite-induced apoptosis (21, 25). Thus, mitochondrial dysfunction may explain the cytotoxicity and degenerative effects induced by arsenic. How ROS links arsenic exposure to carcinogenesis is still not well understood.Vertebrate telomeres consist of tandem repeats of G-rich sequence that cap the ends of chromosomes, protecting them from fusion and chromosomal instability...

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Murine Models of Dysfunctional Telomeres and Telomerase

Liu

Harrington

2012

Telomerases

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An Essential Role for Functional Telomeres in Mouse Germ Cells during Fertilization and Early Development

Cited by 150 publications

References 56 publications

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Oxidative Stress Contributes to Arsenic-induced Telomere Attrition, Chromosome Instability, and Apoptosis

Murine Models of Dysfunctional Telomeres and Telomerase

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