bims-gamemb 2022-03-06 papers

bims-gamemb

Biomed News

on Gamete and embryo metabolism

Issue of 2022–03–06
six papers selected by
Cameron A. Schmidt, East Carolina University

Metabolic exchanges between the oocyte and its environment: focus on lipids.
Glutathione deficiency decreases lipid droplet stores and increases reactive oxygen species in mouse oocytes†.
Peroxiredoxin 4, a new favorable regulator, can protect oocytes against oxidative stress damage during in vitro maturation.
Metabolomic markers of biological fluid in women with reproductive failure: a systematic review of current literatures.
α-Ketoglutarate Improves Meiotic Maturation of Porcine Oocytes and Promotes the Development of PA Embryos, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway.
How the environment affects early embryonic development.

Reprod Fertil Dev. 2021 Dec;34(2): 1-26

Metabolic exchanges between the oocyte and its environment: focus on lipids.

Svetlana Uzbekova, Priscila Silvana Bertevello, Rozenn Dalbies-Tran, Sebastien Elis, Valerie Labas, Philippe Monget, Ana-Paula Teixeira-Gomes.

Finely regulated fatty acid (FA) metabolism within ovarian follicles is crucial to follicular development and influences the quality of the enclosed oocyte, which relies on the surrounding intra-follicular environment for its growth and maturation. A growing number of studies have examined the association between the lipid composition of follicular compartments and oocyte quality. In this review, we focus on lipids, their possible exchanges between compartments within the ovarian follicle and their involvement in different pathways during oocyte final growth and maturation. Lipidomics provides a detailed snapshot of the global lipid profiles and identified lipids, clearly discriminating the cells or fluid from follicles at distinct physiological stages. Follicular fluid appears as a main mediator of lipid exchanges between follicular somatic cells and the oocyte, through vesicle-mediated and non-vesicular transport of esterified and free FA. A variety of expression data allowed the identification of common and cell-type-specific actors of lipid metabolism in theca cells, granulosa cells, cumulus cells and oocytes, including key regulators of FA uptake, FA transport, lipid transformation, lipoprotein synthesis and protein palmitoylation. They act in harmony to accompany follicular development, and maintain intra-follicular homeostasis to allow the oocyte to accumulate energy and membrane lipids for subsequent meiotic divisions and first embryo cleavages.

DOI: https://doi.org/10.1071/RD21249
Biol Reprod. 2022 Mar 03. pii: ioac032. [Epub ahead of print]

Glutathione deficiency decreases lipid droplet stores and increases reactive oxygen species in mouse oocytes†.

Kelli F Malott, Samantha Reshel, Laura Ortiz, Ulrike Luderer.

  Glutathione (GSH) is a tripeptide thiol antioxidant that has been shown to be important to overall reproductive health. Glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis consists of a catalytic and a modifier (GCLM) subunit. We previously showed that oxidative stress in the ovary and oocytes of Gclm-/- mice is associated with accelerated age-related decline in ovarian follicles and decreased female fertility due to preimplantation embryonic mortality. Mammalian preimplantation development is a highly regulated and energy-intensive process that primarily relies on coordination between lipid droplets (LDs) and mitochondria to maintain cellular homeostasis. In this study, we hypothesized that GSH deficiency in oocytes increases oxidative stress, leading to increased mitochondrial dysfunction and decreased LD consumption, thereby decreasing oocyte developmental competence. We observed that Gclm-/- oocytes have increased oxidative stress, primarily in the form of mitochondrial superoxide and decreased subcortical mitochondrial clusters. Further, Gclm-/- oocytes have decreased mitochondrial membrane potential (ΔΨm) compared with Gclm+/+. We surmise this is likely due to the decreased availability of LDs, as we observed a significant decrease in LD content in Gclm-/- oocytes compared with Gclm+/+. The decreased oocyte LD content is likely related to an altered serum lipidome, with Gclm-/- serum having relatively lower unsaturated fatty acids and triglycerides than that of Gclm+/+ and Gclm+/- females. Altogether these data support that decreased LDs and increased oxidative stress are primary drivers of decreased oocyte developmental competence in GSH-deficient oocytes.

Keywords:  glutathione; lipid droplets; lipidomics; mitochondria; oocyte; oxidative stress

DOI:  https://doi.org/10.1093/biolre/ioac032
Biochem Biophys Res Commun. 2022 Feb 19. pii: S0006-291X(22)00238-8. [Epub ahead of print]601 52-58

Peroxiredoxin 4, a new favorable regulator, can protect oocytes against oxidative stress damage during in vitro maturation.

Yi Qian, Xiaofei Zou, Xiuru Liang, Nan Lu, Yugui Cui, Jiayin Liu, Yan Meng.

   BACKGROUND: Finding an effective regulator to avoid harmful effects caused by excessive reactive oxygen species (ROS) is a bottleneck during oocyte in vitro maturation (IVM). Previously, we found that peroxiredoxin 4 (Prdx4) expression is significantly higher in mature cumulus cell-oocyte complexes (COCs) than in immature COCs. Prdx4 belongs to the antioxidant enzyme family and can catalyze the reduction of H2O2.
RESULTS: In this study, we established an oxidative stress model with mouse COCs cultured in vitro. Treatment with H2O2 decreased cumulus expansion indexes and oocyte maturation in a concentration-dependent manner, indicating follicular development dysplasia. Infection with a Prdx4-overexpressing adenovirus significantly attenuated H2O2-induced changes, exhibiting effects similar to those of the intracellular ROS scavenger tiron (the positive control). Furthermore, the results confirmed that the protective effect of Prdx4 on oocyte maturation may be due to reductions in ROS levels and apoptosis. However, when the gap junctions between cumulus cells (CCs) and oocytes were destroyed, Prdx4 overexpression did not exert antiapoptotic effects. The expression levels of the gap junction marker protein CX43 were significantly recovered in the Prdx4-overexpressing group.
CONCLUSIONS: These results demonstrate that Prdx4 in CCs may be a new favorable regulator that improves in vitro-matured oocyte quality and enhances oocyte developmental competence by preventing CC apoptosis caused by oxidative stress through gap junctions. The findings expand the body of knowledge regarding follicle development, and the identification of Prdx4 as a new favorable regulator will aid in immature oocyte IVM.

Keywords:  Cumulus cell-oocyte complex; Follicular development; Gap junction; Oxidative stress; Peroxiredoxin 4

DOI:  https://doi.org/10.1016/j.bbrc.2022.02.049
Biol Reprod. 2022 Feb 28. pii: ioac038. [Epub ahead of print]

Metabolomic markers of biological fluid in women with reproductive failure: a systematic review of current literatures.

Yingying Zhang, Tao Zhang, Ling Wu, Tin Chiu Li, Chi Chiu Wang, Jacqueline Pui Wah Chung.

  Understanding metabolic changes in reproductive failure, including early miscarriage (EM), recurrent miscarriage (RM) and repeated implantation failure (RIF), may be beneficial to understand the pathophysiology, thus improving pregnancy outcomes. Nine metabolomic profiling studies in women with reproductive failures (4 for EM, 3 for RM and 2 for RIF) were included for systematic review. In total 78, 75 and 25 significant metabolites were identified and 40, 40 and 34 metabolic pathways were enriched in EM, RM and RIF, respectively. Among them, 7 and 11 metabolites, and 28 and 28 pathways were shared between EM and RM and between RM and RIF, respectively. Notably, histidine metabolism has the highest impact in EM; phenylalanine, tyrosine and tryptophan biosynthesis. Ubiquinone and other terpenoid-quinone biosynthesis metabolism have the highest impact factor in RM; alanine, aspartate and glutamate metabolism have the highest impact factor in RIF. This study not only summarized the common and distinct metabolites and metabolic pathways in different reproductive failures but also summarized limitations of the study designs and methodologies. Hence, further investigations and validations of these metabolites are still urgently needed to understand the underlying metabolic mechanism for the development and treatment of reproductive failures.

Keywords:  implantation failure; metabolomics; miscarriage; pregnancy; reproductive failure

DOI:  https://doi.org/10.1093/biolre/ioac038
Oxid Med Cell Longev. 2022 ;2022 7113793

α-Ketoglutarate Improves Meiotic Maturation of Porcine Oocytes and Promotes the Development of PA Embryos, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway.

Qiang Chen, Leilei Gao, Jiannan Li, Yitian Yuan, Ruibin Wang, Yiqi Tian, Anmin Lei.

α-Ketoglutarate (α-KG) is a metabolite in the tricarboxylic acid cycle. It has a strong antioxidant function and can effectively prevent oxidative damage. Previous studies have shown that α-KG exists in porcine follicles, and its content gradually increases as the follicles grow and mature. However, the potential mechanism of supplementation of α-KG on porcine oocytes during in vitro maturation (IVM) has not yet been reported. The purpose of this study was to explore the effect of α-KG on the early embryonic development of pigs and the mechanisms underlying these effects. We found that α-KG can enhance the development of early pig embryos. Adding 20 μM α-KG to the in vitro culture medium significantly increased the rate of blastocyst formation and the total cell number. Compared with to that of the control group, apoptosis in blastocysts of the supplement group was significantly reduced. α-KG reduced the production of reactive oxygen species and glutathione levels in cells. α-KG not only improved the activity of mitochondria but also inhibited the occurrence of apoptosis. After supplementation with α-KG, pig embryo pluripotency-related genes (OCT4, NANOG, and SOX2) and antiapoptotic genes (Bcl2) were upregulated. In terms of mechanism, α-KG activates the Nrf2/ARE signaling pathway to regulate the expression of antioxidant-related targets, thus combating oxidative stress during the in vitro culture of oocytes. Activated Nrf2 promotes the transcription of Bcl2 genes and inhibits cell apoptosis. These results indicate that α-KG supplements have a beneficial effect on IVM by regulating oxidative stress during the IVM of porcine oocytes and can be used as a potential antioxidant for IVM of porcine oocytes.

DOI: https://doi.org/10.1155/2022/7113793
Reprod Fertil Dev. 2021 Dec;34(2): 203-213

How the environment affects early embryonic development.

Marc-André Sirard.

In the field of animal reproduction, the environment associated with gametes and embryos refers to the parents' condition as well as conditions surrounding gametes and embryos in vivo or in vitro . This environment is now known to influence not only the functionality of the early embryo but potentially the future phenotype of the offspring. Using transcriptomic and epigenetic molecular analysis, and the bovine model, recent research has shown that both the female and the male metabolic status, for example age, can affect gene expression and gene programming in the embryo. Evidence demonstrates that milking cows, which are losing weight at the time of conception, generates compromised embryos and offspring with a unique metabolic signature. A similar phenomenon has been associated with different culture conditions and the IVF procedure. The general common consequence of these situations is an embryo behaving on 'economy' mode where translation, cell division and ATP production is reduced, potentially to adapt to the perceived future environment. Few epidemiological studies have been done in bovines to assess if these changes result in a different phenotype and more studies are required to associate specific molecular changes in embryos with visible consequences later in life.

DOI: https://doi.org/10.1071/RD21266