bims-gamemb 2022-01-23 papers

bims-gamemb

Biomed News

on Gamete and embryo metabolism

Issue of 2022‒01‒23
eight papers selected by
Cameron A. Schmidt
East Carolina University

Changes in the Mitochondria-Related Nuclear Gene Expression Profile during Human Oocyte Maturation by the IVM Technique.
Mitochondrial DNA content in eggs as a maternal effect.
Energy Metabolism and Hyperactivation of Spermatozoa from Three Mouse Species under Capacitating Conditions.
Sperm metabolic rate predicts female mating frequency across Drosophila species.
Uncovering the important role of mitochondrial dynamics in oogenesis: impact on fertility and metabolic disorder transmission.
Effects of Palmitic Acid on localization of embryo cell fate and blastocyst formation gene products.
REDOX IMBALANCE INDUCES REMODELING OF GLUCOSE METABOLISM IN RHIPICEPHALUS MICROPLUS EMBRYONIC CELL LINE.
Ketogenic diet impairs neurological development of neonatal rats and affects biochemical composition of maternal brains: evidence of functional recovery in pups.

Cells. 2022 Jan 16. pii: 297. [Epub ahead of print]11(2):

Changes in the Mitochondria-Related Nuclear Gene Expression Profile during Human Oocyte Maturation by the IVM Technique.

Zhi-Yong Yang, Min Ye, Ya-Xin Xing, Qi-Gui Xie, Jian-Hong Zhou, Xin-Rui Qi, Kehkooi Kee, Ri-Cheng Chian.

  To address which mitochondria-related nuclear differentially expressed genes (DEGs) and related pathways are altered during human oocyte maturation, single-cell analysis was performed in three oocyte states: in vivo matured (M-IVO), in vitro matured (M-IVT), and failed to mature in vitro (IM-IVT). There were 691 DEGs and 16 mitochondria-related DEGs in the comparison of M-IVT vs. IM-IVT oocytes, and 2281 DEGs and 160 mitochondria-related DEGs in the comparison of M-IVT vs. M-IVO oocytes, respectively. The GO and KEGG analyses showed that most of them were involved in pathways such as oxidative phosphorylation, pyruvate metabolism, peroxisome, and amino acid metabolism, i.e., valine, leucine, isoleucine, glycine, serine, and threonine metabolism or degradation. During the progress of oocyte maturation, the metabolic pathway, which derives the main source of ATP, shifted from glucose metabolism to pyruvate and fatty acid oxidation in order to maintain a low level of damaging reactive oxygen species (ROS) production. Although the immature oocytes could be cultured to a mature stage by an in vitro technique (IVM), there were still some differences in mitochondria-related regulations, which showed that the mitochondria were regulated by nuclear genes to compensate for their developmental needs. Meanwhile, the results indicated that the current IVM culture medium should be optimized to compensate for the special need for further development according to this disclosure, as it was a latent strategy to improve the effectiveness of the IVM procedure.

Keywords:  IVM; RNAseq; cytoplasmic maturation; gene expression; human oocyte; in vitro maturation; mitochondria; oocyte maturation

DOI:  https://doi.org/10.3390/cells11020297
Proc Biol Sci. 2022 Jan 26. 289(1967): 20212100

Mitochondrial DNA content in eggs as a maternal effect.

Sin-Yeon Kim, Violette Chiara, Náyade Álvarez-Quintero, Alberto Velando.

  The transmission of detrimental mutations in animal mitochondrial DNA (mtDNA) to the next generation is avoided by a high level of mtDNA content in mature oocytes. Thus, this maternal genetic material has the potential to mediate adaptive maternal effects if mothers change mtDNA level in oocytes in response to their environment or body condition. Here, we show that increased mtDNA abundance in mature oocytes was associated with fast somatic growth during early development but at the cost of increased mortality in three-spined sticklebacks. We also examined whether oocyte mtDNA and sperm DNA damage levels have interacting effects because they can determine the integrity of mitochondrial and nuclear genes in offspring. The level of oxidative DNA damage in sperm negatively affected fertility, but there was no interacting effect of oocyte mtDNA abundance and sperm DNA damage. Oocyte mtDNA level increased towards the end of the breeding season, and the females exposed to warmer temperatures during winter produced eggs with increased mtDNA copies. Our results suggest that oocyte mtDNA level can vary according to the expected energy demands for offspring during embryogenesis and early growth. Thus, mothers can affect offspring development and viability through the context-dependent effects of oocyte mtDNA abundance.

Keywords:  maternal effect; mitochondria; mtDNA; oocyte; stickleback

DOI:  https://doi.org/10.1098/rspb.2021.2100
Cells. 2022 Jan 10. pii: 220. [Epub ahead of print]11(2):

Energy Metabolism and Hyperactivation of Spermatozoa from Three Mouse Species under Capacitating Conditions.

Ester Sansegundo, Maximiliano Tourmente, Eduardo R S Roldan.

  Mammalian sperm differ widely in sperm morphology, and several explanations have been presented to account for this diversity. Less is known about variation in sperm physiology and cellular processes that can give sperm cells an advantage when competing to fertilize oocytes. Capacitation of spermatozoa, a process essential for mammalian fertilization, correlates with changes in motility that result in a characteristic swimming pattern known as hyperactivation. Previous studies revealed that sperm motility and velocity depend on the amount of ATP available and, therefore, changes in sperm movement occurring during capacitation and hyperactivation may involve changes in sperm bioenergetics. Here, we examine differences in ATP levels of sperm from three mouse species (genus Mus), differing in sperm competition levels, incubated under non-capacitating and capacitating conditions, to analyse relationships between energetics, capacitation, and swimming patterns. We found that, in general terms, the amount of sperm ATP decreased more rapidly under capacitating conditions. This descent was related to the development of a hyperactivated pattern of movement in two species (M. musculus and M. spicilegus) but not in the other (M. spretus), suggesting that, in the latter, temporal dynamics and energetic demands of capacitation and hyperactivation may be decoupled or that the hyperactivation pattern differs. The decrease in ATP levels during capacitation was steeper in species with higher levels of sperm competition than in those with lower levels. Our results suggest that, during capacitation, sperm consume more ATP than under non-capacitating conditions. This higher ATP consumption may be linked to higher velocity and lateral head displacement, which are associated with hyperactivated motility.

Keywords:  ATP; bioenergetics; capacitation; hyperactivation; sperm swimming

DOI:  https://doi.org/10.3390/cells11020220
Evolution. 2022 Jan 21.

Sperm metabolic rate predicts female mating frequency across Drosophila species.

Biz R Turnell, Klaus Reinhardt.

  Female mating rates vary widely, even among closely related species, but the reasons for this variation are not fully understood. Across Drosophila species, female mating frequencies are positively associated with sperm length. This association may be due in part to sperm limitation, with longer-spermed species transferring fewer sperm, or to cryptic female choice. However, a previously overlooked factor is sperm metabolic rate, which may correlate with sperm length. If faster-metabolizing sperm accumulate age-related cellular damage more quickly, then females should remate sooner to obtain fresh sperm. Alternatively, frequent female mating may select for increased sperm competitiveness via increased metabolism. Here, we measure sperm metabolism across 13 Drosophila species and compare these measures to published data on female mating rate and on sperm length. Using fluorescent lifetime imaging microscopy, we quantify NAD(P)H metabolism ex vivo, in intact organs. Phylogenetically controlled regression reveals that sperm metabolic rate is positively associated with sperm length and with female mating frequency. Path analysis shows sperm length driving sperm metabolism and sperm metabolism either driving or being driven by female mating rate. While the causal directionality of these relationships remains to be fully resolved, and the effect of sperm metabolism on sperm aging and/or sperm competitiveness remains to be established, our results demonstrate the importance of sperm metabolism in sexual selection. This article is protected by copyright. All rights reserved.

Keywords:  FLIM; mating rate; oxidative stress; phylogenetic analysis; sperm aging; sperm metabolism

DOI:  https://doi.org/10.1111/evo.14435
Biophys Rev. 2021 Dec;13(6): 967-981

Uncovering the important role of mitochondrial dynamics in oogenesis: impact on fertility and metabolic disorder transmission.

Marcos Roberto Chiaratti.

  Oocyte health is tightly tied to mitochondria given their role in energy production, metabolite supply, calcium (Ca2+) buffering, and cell death regulation, among others. In turn, mitochondrial function strongly relies on these organelle dynamics once cyclic events of fusion and fission (division) are required for mitochondrial turnover, positioning, content homogenization, metabolic flexibility, interaction with subcellular compartments, etc. Importantly, during oogenesis, mitochondria change their architecture from an "orthodox" elongated shape characterized by the presence of numerous transversely oriented cristae to a round-to-oval morphology containing arched and concentrically arranged cristae. This, along with evidence showing that mitochondrial function is kept quiescent during most part of oocyte development, suggests an important role of mitochondrial dynamics in oogenesis. To investigate this, recent works have downregulated/upregulated in oocytes the expression of key effectors of mitochondrial dynamics, including mitofusins 1 (MFN1) and 2 (MFN2) and the dynamin-related protein 1 (DRP1). As a result, both MFN1 and DRP1 were found to be essential to oogenesis and fertility, while MFN2 deletion led to offspring with increased weight gain and glucose intolerance. Curiously, neither MFN1/MFN2 deficiency nor DRP1 overexpression enhanced mitochondrial fragmentation, indicating that mitochondrial size is strictly regulated in oocytes. Therefore, the present work seeks to discuss the role of mitochondria in supporting oogenesis as well as recent findings connecting defective mitochondrial dynamics in oocytes with infertility and transmission of metabolic disorders.

Keywords:  DRP1; Endoplasmic reticulum; MFN1; MFN2; Mitochondria; Oocyte

DOI:  https://doi.org/10.1007/s12551-021-00891-w
Reproduction. 2022 Jan 01. pii: REP-21-0354.R2. [Epub ahead of print]

Effects of Palmitic Acid on localization of embryo cell fate and blastocyst formation gene products.

Michele D Calder, Robert Chen, Anastasia MacDonald, Zoe MacNeily, Zuleika Chin Lai Leung, Samira Adus, Shiyu Cui, Dean Betts, Basim Abu Rafea, Andrew J Watson.

As obese and overweight patients commonly display hyperlipidemia, and are increasingly accessing fertility clinics for their conception needs, our studies are directed at understanding the effects of hyperlipidemia on early pregnancy. We have focused on investigating palmitic acid (PA) and oleic acid (OA) treatment alone and in combination from the mouse two-cell stage as a model for understanding their effects on the mammalian preimplantation embryo. We recently reported that PA exerts a negative effect on mouse two-cell progression to the blastocyst stage, whereas OA co-treatment reverses that negative effect. In the present study, we hypothesized that PA treatment of mouse embryos would disrupt proper localization of cell fate determining and blastocyst formation gene products, and that co-treatment with oleic acid would reverse these effects. Our results demonstrate that PA treatment significantly (p<0.05) reduces blastocyst development and cell number but did not prevent nuclear localization of YAP in outer cells. PA treatment significantly reduced the number of OCT4+ and CDX2+ nuclei. PA treated embryos had lower expression of blastocyst formation proteins (E-cadherin, ZO-1 and Na/K-ATPase alpha1 subunit). Importantly, co-treatment of embryos with OA reversed PA-induced effects on blastocyst development and increased ICM and TE cell numbers and expression of blastocyst formation proteins. Our findings demonstrate that PA treatment does not impede cell fate gene localization but does disrupt proper blastocyst formation gene localization during mouse preimplantation development. OA treatment is protective and reverses PA's detrimental effects. The results advance our understanding of the impact of FFA exposure on mammalian preimplantation development.

DOI: https://doi.org/10.1530/REP-21-0354
J Biol Chem. 2022 Jan 18. pii: S0021-9258(22)00039-4. [Epub ahead of print] 101599

REDOX IMBALANCE INDUCES REMODELING OF GLUCOSE METABOLISM IN RHIPICEPHALUS MICROPLUS EMBRYONIC CELL LINE.

Bárbara Della Noce, Renato Martins da Silva, Marcelle Vianna de Carvalho Uhl, Satoru Konnai, Kazuhiko Ohashi, Christiano Calixto, Angélica Arcanjo, Leonardo Araujo de Abreu, Stephanie Serafim de Carvalho, Itabajara da Silva Vaz, Carlos Logullo.

  Carbohydrate metabolism functions in supplying cellular energy, but also has an important role in maintaining physiological homeostasis and in preventing oxidative damage caused by reactive oxygen species (ROS). Previously, we addressed by studies showing that arthropod embryonic cell lines have high tolerance to H2O2 exposure. Here, we describe that Rhipicephalus microplus tick embryonic cell line (BME26) employs an adaptive glucose metabolism mechanism that confers tolerance to hydrogen peroxide at concentrations too high for other organisms. This adaptive mechanism sustained by glucose metabolism remodeling promotes cell survival and redox balance in BME26 cell line after millimolar H2O2 exposure. The present work shows that this tick cell line could tolerate high H2O2 concentrations by initiating a carbohydrate-related adaptive response. We demonstrate that gluconeogenesis was induced as a compensation strategy that involved, among other molecules, the metabolic enzymes NADP-ICDH, G6PDH, and PEPCK. We also found that this phenomenon was coupled to glycogen accumulation and glucose uptake, supporting the pentose phosphate pathway to sustain NADPH production, and leading to cell survival and proliferation. Importantly, our findings suggest that the described response is not atypical, being also observed in cancer cells, which highlights the importance of this model to all proliferative cells. We propose that these results will be useful in generating basic biological information to support the development of new strategies for disease treatment and parasite control.

Keywords:  Arthropod; Embryogenesis; Glucose; Metabolism; ROS

DOI:  https://doi.org/10.1016/j.jbc.2022.101599
Brain Struct Funct. 2022 Jan 17.

Ketogenic diet impairs neurological development of neonatal rats and affects biochemical composition of maternal brains: evidence of functional recovery in pups.

Kosiek Wojciech, Rauk Zuzanna, Szulc Piotr, Cichy Anna, Rugieł Marzena, Chwiej Joanna, Janeczko Krzysztof, Setkowicz Zuzanna.

  The ketogenic diet (KD) is a type of diet in which the intake of fats significantly increases at the cost of carbohydrates while maintaining an adequate amount of proteins. This kind of diet has been successfully used in clinical therapies of drug-resistant epilepsy, but there is still insufficient evidence on its safety when used in pregnancy. To assess KD effects on the course of gestation and fetal development, pregnant females were fed with: (i) KD during pregnancy and lactation periods (KD group), (ii) KD during pregnancy replaced with ND from the day 2 postpartum (KDND group) and (iii) normal diet alone (ND group). The body mass, ketone and glucose blood levels, and food intake were monitored. In brains of KD-fed females, FTIR biochemical analyses revealed increased concentrations of lipids and ketone groups containing molecules. In offspring of these females, significant reduction of the body mass and delays in neurological development were detected. However, replacement of KD with ND in these females at the beginning of lactation period led to regainment of the body mass in their pups as early as on the postnatal day 14. Moreover, the vast majority of our neurological tests detected functional recovery up to the normal level. It could be concluded that the ketogenic diet undoubtedly affects the brain of pregnant females and impairs the somatic and neurological development of their offspring. However, early postnatal withdrawal of this diet may initiate compensatory processes and considerable functional restitution of the nervous system based on still unrecognized mechanisms.

Keywords:  Betahydroxybutyrate; FTIR spectroscopy; Fetal growth; Ketosis; Undernutrition

DOI:  https://doi.org/10.1007/s00429-021-02450-1