Procyanidin B2 (pcb2) Rescues Mitochondrial Function and Improves The Developmental Potential of Vitrified Oocytes By Regulating Autophagy

The mitochondrion undergoes significant functional and structural changes, as well as an increase in number, during preimplantation embryonic development. The mitochondrion generates ATP and regulates a range of cellular processes, such as signal transduction and apoptosis. Therefore, mitochondria contribute to overall oocyte quality and embryo developmental competence. The present study identified, for the first time, the detailed temporal expression of mRNAs related to mitochondrial biogenesis in rhesus monkey oocytes and embryos. Persistent expression of maternally encoded mRNAs was observed, in combination with transcriptional activation and mRNA accumulation at the eight-cell stage, around the time of embryonic genome activation. The expression of these transcripts was significantly altered in oocytes and embryos with reduced developmental potential. In these embryos, most maternally encoded transcripts were precociously depleted. Embryo culture and specific culture media affected the expression of some of these transcripts, including a deficiency in the expression of key transcriptional regulators. Several genes involved in regulating mitochondrial transcription and replication are similarly affected by in vitro conditions and their downregulation may be instrumental in maintaining the mRNA profiles of mitochondrially encoded genes observed in the present study. These data support the hypothesis that the molecular control of mitochondrial biogenesis, and therefore mitochondrial function, is impaired in in vitro-cultured embryos. These results highlight the need for additional studies in human and non-human primate model species to determine how mitochondrial biogenesis can be altered by oocyte and embryo manipulation protocols and whether this affects physiological function in progeny.

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The Role of Mitochondria in Oocyte Maturation

Cells ◽

10.3390/cells10092484 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2484

Author(s):

Anastasia Kirillova ◽

Johan E. J. Smitz ◽

Gennady T. Sukhikh ◽

Ilya Mazunin

Keyword(s):

Oocyte Maturation ◽

Mitochondrial Function ◽

Animal Cell ◽

Mitochondrial Morphology ◽

Mtdna Copy Number ◽

Cell Organelles ◽

Developmental Potential ◽

The Right

With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for continuous transcription and translation, the availability of the right number of functional mitochondria is crucial. There is a correlation between the quality of oocytes and both the amount of mtDNA and the amount of ATP. Suboptimal conditions of in vitro maturation (IVM) might lead to changes in the mitochondrial morphology as well as alternations in the expression of genes encoding proteins associated with mitochondrial function. Dysfunctional mitochondria have a lower ability to counteract reactive oxygen species (ROS) production which leads to oxidative stress. The mitochondrial function might be improved with the application of antioxidants and significant expectations are laid on the development of new IVM systems supplemented with mitochondria-targeted reagents. Different types of antioxidants have been tested already on animal models and human rescue IVM oocytes, showing promising results. This review focuses on the recent observations on oocytes’ intracellular mitochondrial distribution and on mitochondrial genomes during their maturation, both in vivo and in vitro. Recent mitochondrial supplementation studies, aiming to improve oocyte developmental potential, are summarized.

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Investigation into Developmental Potential and Nuclear/Mitochondrial Function in Early Wood and Plains Bison Hybrid Embryos*

Reproduction in Domestic Animals ◽

10.1111/j.1439-0531.2011.01936.x ◽

2011 ◽

Vol 47 (4) ◽

pp. 644-654 ◽

Cited By ~ 3

Author(s):

RP Seaby ◽

P Mackie ◽

WA King ◽

GF Mastromonaco

Keyword(s):

Mitochondrial Function ◽

Developmental Potential

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Glycine Ameliorates Endoplasmic Reticulum Stress Induced by Thapsigargin in Porcine Oocytes

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.733860 ◽

2021 ◽

Vol 9 ◽

Author(s):

Sicong Yu ◽

Lepeng Gao ◽

Chang Zhang ◽

Yumeng Wang ◽

Hainan Lan ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Mitochondrial Function ◽

Caspase 3 ◽

Polar Body ◽

Free Calcium ◽

Voltage Dependent Anion Channel ◽

Developmental Potential ◽

First Polar Body

The endoplasmic reticulum (ER) is a multifunctional organelle in the cytoplasm that plays important roles in female mammalian reproduction. The endoplasmic reticulum and mitochondria interact to maintain the normal function of cells by maintaining intracellular calcium homeostasis. As proven by previous research, glycine (Gly) can regulate the intracellular free calcium concentration ([Ca2+]i) and enhance mitochondrial function to improve oocyte maturation in vitro. The effect of Gly on ER function during oocyte in vitro maturation (IVM) is not clear. In this study, we induced an ER stress model with thapsigargin (TG) to explore whether Gly can reverse the ER stress induced by TG treatment and whether it is associated with calcium regulation. The results showed that the addition of Gly could improve the decrease in the average cumulus diameter, the first polar body excretion rate caused by TG-induced ER stress, the cleavage rate and the blastocyst rate. Gly supplementation could reduce the ER stress induced by TG by significantly improving the ER levels and significantly downregulating the expression of genes related to ER stress (Xbp1, ATF4, and ATF6). Moreover, Gly also significantly alleviated the increase in reactive oxygen species (ROS) levels and the decrease in mitochondrial membrane potential (ΔΨ m) to improve mitochondrial function in porcine oocytes exposed to TG. Furthermore, Gly reduced the [Ca2+]i and mitochondrial Ca2+ ([Ca2+]m) levels and restored the ER Ca2+ ([Ca2+]ER) levels in TG-exposed porcine oocytes. Moreover, we found that the increase in [Ca2+]i may be caused by changes in the distribution and expression of inositol 1,4,5-triphosphate receptor (IP3R1) and voltage-dependent anion channel 1 (VDAC1), while Gly can restore the distribution and expression of IP3R1 and VDAC1 to normal levels. Apoptosis-related indexes (Caspase 3 activity and Annexin-V) and gene expression Bax, Cyto C, and Caspase 3) were significantly increased in the TG group, but they could be restored by adding Gly. Our results suggest that Gly can ameliorate ER stress and apoptosis in TG-exposed porcine oocytes and can further enhance the developmental potential of porcine oocytes in vitro.

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Assessment of Mitochondrial Function and Developmental Potential of Mouse Oocytes after Mitoquinone Supplementation during Vitrification

Journal of the American Association for Laboratory Animal Science ◽

10.30802/aalas-jaalas-20-000123 ◽

2021 ◽

Author(s):

Maryam H Shirzeyli ◽

Fatemeh Eini ◽

Farshad H Shirzeyli ◽

Saeid A Majd ◽

Mehrdad Ghahremani ◽

...

Keyword(s):

Mitochondrial Function ◽

Mitochondrial Membrane ◽

Membrane Integrity ◽

Atp Depletion ◽

Developmental Competence ◽

Control Group ◽

Nmri Mouse ◽

Developmental Potential ◽

Mouse Oocytes

Vitrification negatively affects the mitochondrial membrane potential (ΔΨm) in oocytes while also leading to increased reactive oxygen species (ROS), ATP depletion and induction of apoptosis in oocytes. Mitoquinone (MitoQ) is an antioxidant that protects mitochondrial membrane integrity from ROS. This study examined the effect of adding MitoQ to vitrification medium on mitochondrial function and embryo development in vitrified oocytes. Metaphase II (MII) stage oocytes were collected from NMRI mouse ovaries and preincubated for 20 min in a medium containing 0.02 µM of MitoQ. Next, oocytes were vitrified in medium supplemented with 0.02 μM of MitoQ (treatment group). The control group was processed in the same way but without exposure to MitoQ. After warming, oocyte survival rate, ΔΨm, cytoplasmic ROS and glutathione (GSH) levels and gene expression levels (Bcl2, BAX, and caspase3) were measured. In addition, the vitrified oocytes were fertilized in-vitro to assess developmental competence. The results showed that MitoQ improved survival and ΔΨm in treated vitrified oocytes. Treated oocytes showed lower ROS levels and higher GSH levels than did the control group. Furthermore, mRNA expression of the Bax/Bcl2 ratio and caspase3 were significantly lower in treated oocytes. These findings indicate that medium supplementation with 0.02 μM of MitoQ during vitrification can improve oocyte survival and developmental competency in mouse oocytes.

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Lysophosphatidic acid improves oocyte quality during IVM by activating the ERK1/2 pathway in cumulus cells and oocytes

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaab032 ◽

2021 ◽

Author(s):

Yerong Ma ◽

Weijie Yang ◽

Peipei Ren ◽

Xiang Li ◽

Jiamin Jin ◽

...

Keyword(s):

Lysophosphatidic Acid ◽

Mitochondrial Function ◽

Polycystic Ovary ◽

Cumulus Cell ◽

Germinal Vesicle ◽

Underlying Mechanism ◽

Oocyte Quality ◽

Developmental Potential ◽

Nuclear Maturation ◽

Cytoplasmic Maturation

Abstract Oocyte IVM technology is an option for fertility preservation in some groups of patients, such as those with polycystic ovary syndrome, patients with ovarian hyperstimulation syndrome, and for patients with cancer. However, the developmental potential of oocytes from IVM still needs to improve. Several previous studies have reported that lysophosphatidic acid (LPA) promotes glucose metabolism, cumulus cell (CC) expansion, and oocyte nuclear maturation. However, the effect of LPA on oocyte cytoplasmic maturation, particularly mitochondrial function, has rarely been studied and the underlying mechanism is largely unknown, which impedes (pre)clinical applications of LPA. In this study, cumulus-oocyte complexes (COCs) and cumulus-denuded germinal vesicle oocytes (DOs) were treated with various concentrations of LPA during IVM, in the presence or absence of the oxidative stressor cyclophosphamide (CTX). In both normal and CTX-damaged COCs, the 25 μM LPA group exhibited improved CC expansion capacity, a higher nuclear maturation rate, and superior mitochondrial function, compared to no LPA treatment. When the concentration of LPA was over 40 μM, detrimental effects of LPA on oocyte maturation occurred. Compared with COCs, the addition of LPA slightly improved oocyte nuclear and cytoplasmic maturation of DOs, but this was not statistically significant. We observed that LPA promotes the activation of ERK1/2, although this was not statistically significant in DOs. Furthermore, LPA could not reverse the negative effect of CC expansion and mitochondrial function after inactivation of ERK1/2 by U0126. RNA-Sequencing and RT-PCR results showed that LPA upregulated several ERK1/2 downstream genes related to CC expansion, such as Areg, Cited4, and Ptgs2. This study demonstrates that LPA improves oocyte quality during IVM through the activation of ERK1/2 pathway CCs and oocytes, which provides evidence for the potential addition of LPA to IVM medium.

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Measuring “Language Access Profiles” in Deaf and Hard-of-Hearing Children With the DHH Language Exposure Assessment Tool

Journal of Speech Language and Hearing Research ◽

10.1044/2020_jslhr-20-00439 ◽

2020 ◽

pp. 1-25

Author(s):

Matthew L. Hall ◽

Stephanie De Anda

Keyword(s):

Cluster Analysis ◽

Exposure Assessment ◽

Hard Of Hearing ◽

Assessment Tool ◽

Communication Mode ◽

Developmental Potential ◽

Language Access ◽

Retest Reliability ◽

Language Exposure ◽

Test Retest Reliability

Purpose The purposes of this study were (a) to introduce “language access profiles” as a viable alternative construct to “communication mode” for describing experience with language input during early childhood for deaf and hard-of-hearing (DHH) children; (b) to describe the development of a new tool for measuring DHH children's language access profiles during infancy and toddlerhood; and (c) to evaluate the novelty, reliability, and validity of this tool. Method We adapted an existing retrospective parent report measure of early language experience (the Language Exposure Assessment Tool) to make it suitable for use with DHH populations. We administered the adapted instrument (DHH Language Exposure Assessment Tool [D-LEAT]) to the caregivers of 105 DHH children aged 12 years and younger. To measure convergent validity, we also administered another novel instrument: the Language Access Profile Tool. To measure test–retest reliability, half of the participants were interviewed again after 1 month. We identified groups of children with similar language access profiles by using hierarchical cluster analysis. Results The D-LEAT revealed DHH children's diverse experiences with access to language during infancy and toddlerhood. Cluster analysis groupings were markedly different from those derived from more traditional grouping rules (e.g., communication modes). Test–retest reliability was good, especially for the same-interviewer condition. Content, convergent, and face validity were strong. Conclusions To optimize DHH children's developmental potential, stakeholders who work at the individual and population levels would benefit from replacing communication mode with language access profiles. The D-LEAT is the first tool that aims to measure this novel construct. Despite limitations that future work aims to address, the present results demonstrate that the D-LEAT represents progress over the status quo.

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