The Role of Mitochondria in Human Fertility and Early Embryo Development: What Can We Learn for Clinical Application of Assessing and Improving Mitochondrial DNA?

Podolak, Amira; Wocławek-Potocka, Izabela; Łukaszuk, Krzysztof

doi:10.3390/cells11050797

Cited by 28 publications

(29 citation statements)

References 109 publications

(332 reference statements)

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“…It has been reported that mitochondria have a significant contribution to regulating the various physiological aspects of reproductive processes. Normally functioning mitochondria and intact mitochondrial membrane potential are a pre-requisite for normal sperm motility (Piomboni et al, 2012;Dutta et al, 2019;Ribeiro et al, 2021), hyperactivation (Dutta et al, 2019), capacitation (Jha et al, 2003;Bailey, 2010;Aitken, 2017;Dutta et al, 2019), acrosin activity (Breitbart, 2003), acrosome reaction (Breitbart, 2003;Gupta and Bhandari, 2011)and DNA integrity (Sakkas and Alvarez, 2010;Mallidis and Wistuba, 2018;Durairajanayagam et al, 2021;Podolak et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

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Decoding the role of cytochrome c in metabolism of human spermatozoa by Raman imaging

Abramczyk

Sobkiewicz²,

Walczak-Jędrzejowska³

et al. 2022

Front. Cell Dev. Biol.

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The normal functioning of sperm cells requires cytochrome c in the redox balanced forms: reduced and oxidized. The oxidized form of cytochrome c is localized in the mitochondrial intermembrane space and is a part of the electron transport chain. This ensures that electron shuttling between the complex III, cytochrome c, and complex IV can occur leading to controlled effective oxidative phosphorylation (respiration) and ATP production needed for most steps in spermatozoal maturation, motility, hyperactivation and fertilization. We studied the biochemical composition of specific organelles in sperm cells by Raman imaging. The structures of the head consisting of the nucleus and acrosome, the midpiece representing mitochondria, and the tail characterized by the sperm axoneme surrounded by outer dense fiber and covered by the membrane were measured. Metabolic biochemical analysis of mitochondria, head and tail of sperm cells, and seminal plasma by using Raman imaging combined with chemometric classification method of Cluster Analysis has been obtained. Our results show that cytochrome c, which is a key protein that is needed to maintain life (respiration) and cell death (apoptosis), is located in sperm mitochondria in the oxidized or reduced form of the heme group. This work demonstrated that an application of Raman micro-spectroscopy can be extended to monitoring the redox state of mitochondrial cytochrome c in sperm cells.

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Section: Discussionmentioning

confidence: 99%

“…Frontiers in Cell and Developmental Biology frontiersin.org 2011; Aitken, 2017;Dutta et al, 2019;Ribeiro et al, 2021;Podolak et al, 2022) for semen quality and human sperm function in fertilization. However, the precise role of mitochondria in spermatozoa remains to be fully explored.…”

Section: The Redox Balance Of Cytochrome In the Midpiece Region Of Mi...mentioning

confidence: 99%

Decoding the role of cytochrome c in metabolism of human spermatozoa by Raman imaging

Abramczyk

Sobkiewicz²,

Walczak-Jędrzejowska³

et al. 2022

Front. Cell Dev. Biol.

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“…The control of reproductive behavior is tightly linked to the functional cellular/tissue mechanisms associated with energy metabolism and food availability [59,98,122,[183][184][185]. As reproductive behavior and physiology are tightly controlled at certain points in the lifespan, it is not surprising that the broader relaxin system likely intersects with this aging-reproduction nexus.…”

Section: Reproductive Agingmentioning

confidence: 99%

The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease

Leysen

Walter

Clauwaert

et al. 2022

IJMS

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During the aging process our body becomes less well equipped to deal with cellular stress, resulting in an increase in unrepaired damage. This causes varying degrees of impaired functionality and an increased risk of mortality. One of the most effective anti-aging strategies involves interventions that combine simultaneous glucometabolic support with augmented DNA damage protection/repair. Thus, it seems prudent to develop therapeutic strategies that target this combinatorial approach. Studies have shown that the ADP-ribosylation factor (ARF) GTPase activating protein GIT2 (GIT2) acts as a keystone protein in the aging process. GIT2 can control both DNA repair and glucose metabolism. Through in vivo co-regulation analyses it was found that GIT2 forms a close coexpression-based relationship with the relaxin-3 receptor (RXFP3). Cellular RXFP3 expression is directly affected by DNA damage and oxidative stress. Overexpression or stimulation of this receptor, by its endogenous ligand relaxin 3 (RLN3), can regulate the DNA damage response and repair processes. Interestingly, RLN3 is an insulin-like peptide and has been shown to control multiple disease processes linked to aging mechanisms, e.g., anxiety, depression, memory dysfunction, appetite, and anti-apoptotic mechanisms. Here we discuss the molecular mechanisms underlying the various roles of RXFP3/RLN3 signaling in aging and age-related disorders.

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“…Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen encoded proteins are involved in oxidative phosphorylation [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Does Trophectoderm Mitochondrial DNA Content Affect Embryo Developmental and Implantation Potential?

Łukaszuk

Podolak

2022

IJMS

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A retrospective case control study was undertaken at the molecular biology department of a private center for reproductive medicine in order to determine whether any correlation exists between the mitochondrial DNA (mtDNA) content of trophectoderm and embryo developmental potential. A total of 275 couples underwent IVF treatment, producing a total of 716 embryos. The trophectoderm was biopsied from each embryo at the blastocyst stage (day 5 or day 6 post-fertilization) subjected to low-pass next-generation sequencing (NGS), for the purpose of detecting aneuploidy. For each sample, the number of mtDNA reads obtained after analysis using NGS was divided by the number of reads attributable to the nuclear genome. The mtDNA copy number was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 1.13 ± 1.37 versus 1.45 ± 1.78, p = 0.02) and in day 5 biopsies compared to day 6 biopsies (1.41 ± 1.66 vs. 1.19 ± 1.27, p = 0.001), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (1.58 ± 2.44 vs. 2.19 ± 2.89, p = 0.12), genetic sex (1.27 ± 1.29 vs. 1.27 ± 1.18, p = 0.99), maternal age (1.31 ± 1.41 vs. 1.33 ± 1.29, p = 0.43), or its ability to implant (1.14 ± 0.88 vs. 1.21 ± 1.16, p = 0.39). mtDNA has small potential to serve as an additional, independent biomarker for embryo selection.

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The Role of Mitochondria in Human Fertility and Early Embryo Development: What Can We Learn for Clinical Application of Assessing and Improving Mitochondrial DNA?

Cited by 28 publications

References 109 publications

Decoding the role of cytochrome c in metabolism of human spermatozoa by Raman imaging

Decoding the role of cytochrome c in metabolism of human spermatozoa by Raman imaging

The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease

Does Trophectoderm Mitochondrial DNA Content Affect Embryo Developmental and Implantation Potential?

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