Fragmentation of embryos is associated with both necrosis and apoptosis

Chi, Hee-Jun; Koo, Jung-Jin; Choi, S.Y.; Jeong, Hyeon-Jeong; Roh, Sangho

doi:10.1016/j.fertnstert.2011.04.020

Cited by 44 publications

(32 citation statements)

References 31 publications

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“…Embryo fragmentation is clinically considered as an indicator of reduced embryo viability and developmental ability, reduced number of high quality embryos available for establishing pregnancies, thus as a relevant problem for assisted reproduction outcome. In fresh embryos, blastomere fragmentation has been reported to be associated to apoptosis [24,35,36] or to apoptosis and necrosis [37]. A recent study [36] revealed novel early transcription mechanisms by which maternal genotype affects cytofragmentation by alterating regular cytoskeletal functions.…”

Section: Discussionmentioning

confidence: 99%

Vitrification preserves chromatin integrity, bioenergy potential and oxidative parameters in mouse embryos

Martino

Dell’Aquila

Cardone

et al. 2013

Reprod Biol Endocrinol

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BackgroundThe aim of this study was to evaluate the effects of vitrification on morpho-functional parameters (blastomere/chromatin integrity and bioenergy/oxidative potential) of mouse preimplantation embryos.MethodsIn vivo produced mouse (4/16-cell, morulae and blastocyst-stage) embryos were randomly divided into vitrification and control groups. For vitrification, embryos were exposed to a 2-step loading of ethylene glycol and propylene glycol, before being placed in a small nylon loop and submerged into liquid nitrogen. After warming, the cryoprotectants were diluted by a 3-step procedure. Embryo morphology, chromatin integrity and energy/oxidative status were compared between groups.ResultsVitrification induced low grade blastomere cytofragmentation (P < 0.05) and low chromatin damage only in embryos at the morula stage (P < 0.001). Mitochondrial (mt) distribution pattern was affected by vitrification only in early embryos (P < 0.001). Mitochondrial activity did not change upon vitrification in morula-stage embryos but it was reduced in blastocyst-stage embryos (P < 0.05). Intracellular ROS levels significantly increased in embryos at the morula and blastocyst stages (P < 0.001). Colocalization of active mitochondria and ROS increased only in vitrified blastocysts.ConclusionsIn conclusion, this study elucidates the developmentally-related and mild effects of vitrification on morphology, nuclear and bioenergy/oxidative parameters of mouse embryos and demonstrates that vitrification is a suitable method for preserving predictive parameters of embryo ability to induce a full-term pregnancy.

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Section: Discussionmentioning

confidence: 99%

Vitrification preserves chromatin integrity, bioenergy potential and oxidative parameters in mouse embryos

Martino

Dell’Aquila

Cardone

et al. 2013

Reprod Biol Endocrinol

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“…Embryo fragments have been reported to cause apoptosis or necrosis in blastomeres and to adversely affect the development of surrounding blastomeres by secreting harmful substances such as reactive oxygen species [6912172023]. Embryo fragments first appear during the initial cleavage process of zygotes on day 2 in vitro , and the proportion of fragments gradually increases during subsequent in vitro culture.…”

Section: Discussionmentioning

confidence: 99%

“…These fragments have been shown to secrete harmful substances that adversely affect the surrounding healthy cells, resulting in impaired embryo development [12], decreased implantation potential and pregnancy rate, and an increased abortion rate [2891011141516]. Furthermore, excessive fragments may induce arrest of embryo development, apoptosis and necrosis of blastomeres, and abnormal embryo development, compaction, and blastocyst formation [617]. …”

Section: Introductionmentioning

confidence: 99%

Early fragment removal on in vitro fertilization day 2 significantly improves the subsequent development and clinical outcomes of fragmented human embryos

Kim¹,

Kim²,

Park³

et al. 2018

Clin Exp Reprod Med

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ObjectiveTo determine whether fragment removal on in vitro fertilization (IVF) day 2 improved the subsequent development and pregnancy outcomes of fragmented embryos compared to similar-grade embryos without fragment removal.MethodsThis study was a retrospective analysis involving 191 IVF cycles in which all embryos had over 10% fragmentation (grade 3 or 4) on day 2 of the IVF-embryo transfer cycle from March 2015 to December 2017. IVF cycles were divided into the fragment removal group (n=87) and the no fragment removal group (n=104) as a control cohort. Before fragment removal, embryos with fragmentation on day 2 were incubated in Ca2+- and Mg2+-free biopsy medium under paraffin oil for 30 minutes. Microsurgical fragment removal was performed with later-assisted hatching and a handmade suction micropipette that had an outer diameter of 30 µm.ResultsThere were no significant differences in the characteristics of the patients between the control and the fragment removal groups. After fragment removal and subsequent in vitro culture for 24 hours, the number of blastomeres (7.1±1.7 vs. 6.9±1.6) was comparable between the transferred embryos in the two groups, but the morphological grade of the embryos in the fragment removal group (1.9±0.7) was significantly higher than that of the control group (3.1±0.5, p<0.01). The clinical pregnancy (43.7%) and implantation rates (25.8%) in the fragment removal group were significantly higher than those in the control group (28.8% and 14.0%, respectively; p<0.05).ConclusionEarly fragment removal on day 2 significantly improved the subsequent development and pregnancy outcomes of fragmented embryos.

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“…In addition, the fragmentation was increased in multinucleated embryos of Kid KD in the present study during cell division. It was reported that fragmented blastomeres decrease adenosine triphosphate production in the cell, resulted in decreasing the developmental competence in vitro (Chi et al ). Considering these facts, the lower developmental competence of Kid KD embryos seems to be depended on the detrimental effects of multinucleous formation.…”

Section: Discussionmentioning

confidence: 99%

Kid depletion in mouse oocytes associated with multinucleated blastomere formation and inferior embryo development

Egashira¹,

Yamauchi

Islam

et al. 2016

Animal Science Journal

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This study investigated the knockdown (KD) of Kid on maturation developmental competence and multinucleation of mouse germinal vesicle (GV) oocytes after parthenogenetic activation. Data revealed that Kid messenger RNA (mRNA) was expressed in GV and MII stage oocyte and 1- and 2-cell embryos. Additionally, Kid mRNA expression in the Kid KD group decreased by nearly 46% compared to the control small interfering RNA (siRNA) groups. The rate of multinucleated embryos in the Kid KD group (52.4%) was significantly higher (P < 0.05) than the control siRNA group (4.7%). Finally, the developmental rates were significantly lower in the Kid siRNA group at > 4-cell stage (28.6% vs. 53.5%) and the blastocyst stage (2.4% vs. 23.3%) compared to the control siRNA groups. Suppression of Kid using siRNA caused multinucleation in early embryos with high frequency and it may increase 2- to 4-cell arrested embryos and reduce the developmental competence to blastocyst.

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Fragmentation of embryos is associated with both necrosis and apoptosis

Cited by 44 publications

References 31 publications

Vitrification preserves chromatin integrity, bioenergy potential and oxidative parameters in mouse embryos

Vitrification preserves chromatin integrity, bioenergy potential and oxidative parameters in mouse embryos

Early fragment removal on in vitro fertilization day 2 significantly improves the subsequent development and clinical outcomes of fragmented human embryos

Kid depletion in mouse oocytes associated with multinucleated blastomere formation and inferior embryo development

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