Overexpression of cyclin A1 promotes meiotic resumption but induces premature chromosome separation in mouse oocyte

Abstract Background：Methotrexate (MTX) is an antifolate agent which is widely used in clinic for treating malignancies, rheumatoid arthritis and ectopic pregnancy. As reported, MTX has side effects on gastrointestinal system, nervous system and reproductive system, while its potential damages on oocyte quality are still unclear. It is known that oocyte quality is essential for healthy conception and the forthcoming embryo development. Thus, this work studied the effects of MTX on the oocyte quality. Results: We established MTX model mice by single treatment with 5 mg/Kg MTX. Both morphological and molecular biology studies were performed to assess the in-vivo matured oocytes quality and to analyze the related mechanisms. The in-vivo matured oocytes from MTX-treated mice had poor in-vitro fertilization ability, and the resulting embryo formation rates and blastocyst quality were lower than the control group. We found that the in-vivo matured MTX-treated mouse oocytes displayed abnormal transcript expressions for genes of key enzymes in the folate cycles. MTX increased the rate of abnormal chromosome alignment and affected the regulation of chromosome separation via disrupting the spindle morphology and reducing the mRNA expressions of MAD2 and Sgo1. MTX reduced the DNA methylation levels in the in-vivo matured oocytes, and further studies showed that MTX altered the expressions of DNMT1 and DNMT 3b, and may also affect the levels of the methyl donor and its metabolite. Conclusions: MTX impaired the in-vivo matured mouse oocyte quality by disturbing folate metabolism and affecting chromosome stability and methylation modification.

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Posttranscriptional Regulation of Cyclin A1 and Cyclin A2 During Mouse Oocyte Meiotic Maturation and Preimplantation Development1

Biology of Reproduction ◽

10.1095/biolreprod65.4.986 ◽

2001 ◽

Vol 65 (4) ◽

pp. 986-993 ◽

Cited By ~ 38

Author(s):

Dai-ichiro Fuchimoto ◽

Aki Mizukoshi ◽

Richard M. Schultz ◽

Senkiti Sakai ◽

Fugaku Aoki

Keyword(s):

Posttranscriptional Regulation ◽

Mouse Oocyte ◽

Meiotic Maturation ◽

Cyclin A1 ◽

Cyclin A2 ◽

Oocyte Meiotic Maturation

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Small GTPase RhoA is required for ooplasmic segregation and spindle rotation, but not for spindle organization and chromosome separation during mouse oocyte maturation, fertilization, and early cleavage

Molecular Reproduction and Development ◽

10.1002/mrd.20253 ◽

2005 ◽

Vol 71 (2) ◽

pp. 256-261 ◽

Cited By ~ 38

Author(s):

Zhi-Sheng Zhong ◽

Li-Jun Huo ◽

Cheng-Guang Liang ◽

Da-Yuan Chen ◽

Qing-Yuan Sun

Keyword(s):

Oocyte Maturation ◽

Small Gtpase ◽

Mouse Oocyte ◽

Early Cleavage ◽

Spindle Rotation ◽

Chromosome Separation ◽

Ooplasmic Segregation

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Methotrexate impaired in-vivo matured mouse oocyte quality and the possible mechanisms

10.21203/rs.2.18530/v1 ◽

2019 ◽

Author(s):

Ning Tian ◽

Dan-yu Lv ◽

Ji Yu ◽

Wan-yun Ma

Keyword(s):

Oocyte Quality ◽

Mouse Oocyte ◽

Control Group ◽

Vitro Fertilization ◽

Embryo Formation ◽

Blastocyst Quality ◽

Chromosome Alignment ◽

Chromosome Separation

Abstract Background: Methotrexate (MTX) is an antifolate agent which is widely used in clinic for treating malignancies, rheumatoid arthritis and ectopic pregnancy. As reported, MTX has side effects on gastrointestinal system, nervous system and reproductive system, while its potential damages on oocyte quality are still unclear. It is known that oocyte quality is essential for healthy conception and the forthcoming embryo development. Thus, this work studied the effects of MTX on the oocyte quality. Results: We established MTX model mice by single treatment with 5 mg/Kg MTX. Both morphological and molecular biology studies were performed to assess the in-vivo matured oocytes quality and to analyze the related mechanisms. The in-vivo matured oocytes from MTX-treated mice had poor in-vitro fertilization ability, and the resulting embryo formation rates and blastocyst quality were lower than the control group. We found that the in-vivo matured MTX-treated mouse oocytes displayed abnormal transcript expressions for genes of key enzymes in the folate cycles. MTX increased the rate of abnormal chromosome alignment and affected the regulation of chromosome separation via disrupting the spindle morphology and reducing the mRNA expressions of MAD2 and Sgo1. MTX reduced the DNA methylation levels in the in-vivo matured oocytes, and further studies showed that MTX altered the expressions of DNMT1 and DNMT 3b, and may also affect the levels of the methyl donor and its metabolite. Conclusions: MTX impaired the in-vivo matured mouse oocyte quality by disturbing folate metabolism and affecting chromosome stability and methylation modification.

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Methotrexate impaired in-vivo matured mouse oocyte quality and the possible mechanisms

10.21203/rs.2.18530/v4 ◽

2020 ◽

Author(s):

Ning Tian ◽

Dan-yu Lv ◽

Ji Yu ◽

Wan-yun Ma

Keyword(s):

Oocyte Quality ◽

Mouse Oocyte ◽

Control Group ◽

Single Treatment ◽

Embryo Formation ◽

Blastocyst Quality ◽

Chromosome Alignment ◽

Chromosome Separation

Abstract Background：Methotrexate (MTX) is an antifolate agent which is widely used in clinic for treating malignancies, rheumatoid arthritis and ectopic pregnancy. As reported, MTX has side effects on gastrointestinal system, nervous system and reproductive system, while its potential damages on oocyte quality are still unclear. It is known that oocyte quality is essential for healthy conception and the forthcoming embryo development. Thus, this work studied the effects of MTX on the oocyte quality. Results: We established MTX model mice by single treatment with 5 mg/Kg MTX. Both morphological and molecular biology studies were performed to assess the in-vivo matured oocytes quality and to analyze the related mechanisms. The in-vivo matured oocytes from MTX-treated mice had poor in-vitro fertilization ability, and the resulting embryo formation rates and blastocyst quality were lower than the control group. We found that the in-vivo matured MTX-treated mouse oocytes displayed abnormal transcript expressions for genes of key enzymes in the folate cycles. MTX increased the rate of abnormal chromosome alignment and affected the regulation of chromosome separation via disrupting the spindle morphology and reducing the mRNA expressions of MAD2 and Sgo1. MTX reduced the DNA methylation levels in the in-vivo matured oocytes, and further studies showed that MTX altered the expressions of DNMT1 and DNMT 3b, and may also affect the levels of the methyl donor and its metabolite. Conclusions: MTX impaired the in-vivo matured mouse oocyte quality by disturbing folate metabolism and affecting chromosome stability and methylation modification.

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Methotrexate impaired in-vivo matured mouse oocyte quality and the possible mechanisms

10.21203/rs.2.18530/v2 ◽

2020 ◽

Author(s):

Ning Tian ◽

Dan-yu Lv ◽

Ji Yu ◽

Wan-yun Ma

Keyword(s):

Oocyte Quality ◽

Mouse Oocyte ◽

Control Group ◽

Vitro Fertilization ◽

Embryo Formation ◽

Blastocyst Quality ◽

Chromosome Alignment ◽

Chromosome Separation

Abstract Background: Methotrexate (MTX) is an antifolate agent which is widely used in clinic for treating malignancies, rheumatoid arthritis and ectopic pregnancy. As reported, MTX has side effects on gastrointestinal system, nervous system and reproductive system, while its potential damages on oocyte quality are still unclear. It is known that oocyte quality is essential for healthy conception and the forthcoming embryo development. Thus, this work studied the effects of MTX on the oocyte quality. Results: We established MTX model mice by single treatment with 5 mg/Kg MTX. Both morphological and molecular biology studies were performed to assess the in-vivo matured oocytes quality and to analyze the related mechanisms. The in-vivo matured oocytes from MTX-treated mice had poor in-vitro fertilization ability, and the resulting embryo formation rates and blastocyst quality were lower than the control group. We found that the in-vivo matured MTX-treated mouse oocytes displayed abnormal transcript expressions for genes of key enzymes in the folate cycles. MTX increased the rate of abnormal chromosome alignment and affected the regulation of chromosome separation via disrupting the spindle morphology and reducing the mRNA expressions of MAD2 and Sgo1. MTX reduced the DNA methylation levels in the in-vivo matured oocytes, and further studies showed that MTX altered the expressions of DNMT1 and DNMT 3b, and may also affect the levels of the methyl donor and its metabolite. Conclusions: MTX impaired the in-vivo matured mouse oocyte quality by disturbing folate metabolism and affecting chromosome stability and methylation modification.

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Spindle scaling mechanisms

Essays in Biochemistry ◽

10.1042/ebc20190064 ◽

2020 ◽

Vol 64 (2) ◽

pp. 383-396

Author(s):

Lara K. Krüger ◽

Phong T. Tran

Keyword(s):

Cell Size ◽

Spindle Assembly ◽

Dependent Manner ◽

Post Translational Modification ◽

Size Dependent ◽

A Cell ◽

Chromosome Separation ◽

Spindle Elongation ◽

Protein Gradients ◽

Spindle Structure

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.

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