The Role of Mitochondria in Oocyte and Early Embryo Health

Kim, Kyunga; Kenigsberg, Shlomit; Jurisicova, Andrea; Bentov, Yaakov

doi:10.21926/obm.genet.1901070

Cited by 10 publications

(7 citation statements)

References 157 publications

(199 reference statements)

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“…These activities require, apart from cellular proteostasis, properly functioning cell cycle machinery and high energy to conduct. In addition to ATP production, mitochondria perform a number of functions that are vital for embryo survival, including intracellular calcium sequestration and release, free fatty acid synthesis, regulation of cell death and serving as a repository of intact mitochondrial DNA (mtDNA) for developing offspring [ 50 , 51 ]. Deficiencies in mitochondrial function and mtDNA number have been shown to impact egg quality and developmental competence in different yet overlapping ways [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Knock out of specific maternal vitellogenins in zebrafish (Danio rerio) evokes vital changes in egg proteomic profiles that resemble the phenotype of poor quality eggs

et al. 2021

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Background We previously reported the results of CRISPR/Cas9 knock-out (KO) of type-I and type-III vitellogenins (Vtgs) in zebrafish, which provided the first experimental evidence on essentiality and disparate functioning of Vtgs at different stages during early development. However, the specific contributions of different types of Vtg to major cellular processes remained to be investigated. The present study employed liquid chromatography and tandem mass spectrometry (LC-MS/MS) to meet this deficit. Proteomic profiles of zebrafish eggs lacking three type-I Vtgs simultaneously (vtg1-KO), or lacking only type III Vtg (vtg3-KO) were compared to those of wild type (Wt) eggs. Obtained spectra were searched against a zebrafish proteome database and identified proteins were quantified based on normalized spectral counts. Results The vtg-KO caused severe changes in the proteome of 1-cell stage zebrafish eggs. These changes were disclosed by molecular signatures that highly resembled the proteomic phenotype of poor quality zebrafish eggs reported in our prior studies. Proteomic profiles of vtg-KO eggs and perturbations in abundances of hundreds of proteins revealed unique, noncompensable contributions of multiple Vtgs to protein and in energy homeostasis. The lack of this contribution appears to have a significant impact on endoplasmic reticulum and mitochondrial functions, and thus embryonic development, even after zygotic genome activation. Increased endoplasmic reticulum stress, Redox/Detox activities, glycolysis/gluconeogenesis, enrichment in cellular proliferation and in human neurodegenerative disease related activities in both vtg1- and vtg3-KO eggs were found to be indicators of the aforementioned conditions. Distinctive increase in apoptosis and Parkinson disease pathways, as well as the decrease in lipid metabolism related activities in vtg3-KO eggs implies compelling roles of Vtg3, the least abundant form of Vtgs in vertebrate eggs, in mitochondrial activities. Several differentially abundant proteins representing the altered molecular mechanisms have been identified as strong candidate markers for studying the details of these mechanisms during early embryonic development in zebrafish and possibly other vertebrates. Conclusions These findings indicate that the global egg proteome is subject to extensive modification depending on the presence or absence of specific Vtgs and that these modifications can have a major impact on developmental competence.

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Section: Discussionmentioning

confidence: 99%

Knock out of specific maternal vitellogenins in zebrafish (Danio rerio) evokes vital changes in egg proteomic profiles that resemble the phenotype of poor quality eggs

et al. 2021

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“…Several studies have shown that apoptosis is involved in the pathogenesis of renal diseases (27). Apoptosis has two pathways (i.e., exogenous and endogenous) (28), and the endogenous pathway can be further divided into mitochondrial pathways and endoplasmic reticulum pathways (29)(30)(31). In our study, as the key factor in mitochondrial apoptosis, the decreased of Bcl-2 and the upregulation of Bax in the I/R-induced AKI and CKD models might indicate the occurrence of mitochondrial apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV protects against ischemia/reperfusion (I/R)-induced kidney injury based on the Keap1-Nrf2/ARE signaling pathway

Y¹,

Chen²,

Feng³

et al. 2022

Transl Androl Urol

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Background: This study sought to investigate the protective effects of Astragaloside IV (AS-IV) on ischemia-reperfusion (I/R) renal injury based on the keap1-Nrf2/ARE signaling pathway.Methods: A total of 36 male Sprague-Dawley rats (aged: 8 weeks; weighing: 200-220 g) were randomly divided into the following 6 groups (n=6 per group): (I) the control group; (II) the sham operation group;(III) the kidney I/R injury group (the I/R group); (IV) the kidney I/R injury group treated with 2 mg/kg of AS-IV (the low-dose group); (V) the kidney I/R injury group treated with 5 mg/kg of AS-IV (the mid-dose group); and (VI) the kidney I/R injury group treated with 10 mg/kg of AS-IV (the high-dose group). Serum creatinine (CRE), serum urea, malondialdehyde (MDA), and superoxide dismutase (SOD) were examined using enzyme-linked immunoassay kits. Cell apoptosis and the pathological damage to the renal tissue were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling, hematoxylin and eosin, and periodic acid-Schiff (PAS) staining. The immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and western blot methods were used to determine the expression of Nrf2, HO-1, Bcl-2 and Bax in the kidney tissue.Results: In the I/R rat model, the serum CRE level was increased. In the acute kidney injury (AKI) and chronic kidney disease (CKD) models, AS-IV treatment significantly decreased serum CRE levels in a dosedependent manner. AS-IV treatment also reduced the injury of renal tubular epithelial cells, increased the expression levels of Nrf2 and HO-1, decreased the rate of apoptosis, downregulated the level of MDA, and elevated the activity of SOD. In the CKD rat model, the AS-IV treatment groups had reduced renal tubular epithelial cell injury, increased expression levels of Nrf2 and HO-1, decreased MDA levels, and increased SOD activity compared to the I/R group.Conclusions: AS-IV induced the expression of Nrf2, enhanced the activity of antioxidant enzymes, reduced apoptosis, protected against renal I/R injury, and prevented AKI from transforming into CKD.These findings suggest that AS-IV is a promising drug for treating kidney injury.

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“…However, previous study ( Thundathil et al, 2005 ) has suggested that once ovulation, mtDNA replication is suspended and organelles are divided into a single blastomere through several rounds of cell divisions. Despite multiple cell divisions, the mtDNA copy number of each embryo does not change until the blastocyst stage (day 5–6 embryo) ( Kim et al, 2019 ). As for the enhanced fluorescence of mitochondria in morula stage, it may be just a manifestation of enhanced mitochondrial activity to meet the needs of embryonic development, rather than the proliferation of mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression Profiles and Potential Intergenerational Functions of tRNA-Derived Small RNAs in Mice After Cadmium Exposure

Zhou

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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Cadmium (Cd) is a toxic heavy metal and ubiquitous environmental endocrine disruptor. Previous studies on Cd-induced damage to male fertility mainly focus on the structure and function of testis, including cytoskeleton, blood-testis barrier, and steroidogenesis. Nevertheless, to date, no studies have investigated the effects of Cd exposure on sperm epigenetic inheritance and intergenerational inheritance. In our study, we systematically revealed the changes in sperm tRNA-derived small RNAs (tsRNA) profiles and found that 14 tsRNAs (9 up-regulated and 5 down-regulated) were significantly altered after Cd exposure. Bioinformatics of tsRNA-mRNA-pathway interactions revealed that the altered biological functions mainly were related to ion transmembrane transport, lipid metabolism and cell membrane system. In addition, we focused on two stages of early embryo development and selected two organs to study the impact of these changes on cell membrane system, especially mitochondrion and lysosome, two typical membrane-enclosed organelles. Surprisingly, we found that the content of mitochondrion was significantly decreased in 2-cell stage, whereas remarkably increased in the morula stage. The contents of mitochondrion and lysosome were increased in the testes of 6-day-old offspring and livers of adult offspring, whereas remarkably decreased in the testes of adult offspring. This provides a possible basis to further explore the effects of paternal Cd exposure on offspring health.

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The Role of Mitochondria in Oocyte and Early Embryo Health

Cited by 10 publications

References 157 publications

Knock out of specific maternal vitellogenins in zebrafish (Danio rerio) evokes vital changes in egg proteomic profiles that resemble the phenotype of poor quality eggs

Knock out of specific maternal vitellogenins in zebrafish (Danio rerio) evokes vital changes in egg proteomic profiles that resemble the phenotype of poor quality eggs

Astragaloside IV protects against ischemia/reperfusion (I/R)-induced kidney injury based on the Keap1-Nrf2/ARE signaling pathway

Differential Expression Profiles and Potential Intergenerational Functions of tRNA-Derived Small RNAs in Mice After Cadmium Exposure

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