Trace mineral mixture supplemented to in vitro maturation medium improves subsequent embryo development and embryo quality in cattle

Anchordoquy, Juan Patricio; Balbi, M.; Farnetano, Nicolás Agustín; Fabra, Mariana Carolina; Carranza-Martín, Ana C.; Nikoloff, Noelia; Giovambattista, G.; Furnus, Cecilia Cristina; Anchordoquy, Juan Mateo

doi:10.1007/s11259-022-09982-9

Cited by 5 publications

(4 citation statements)

References 49 publications

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“…Whether 20.90 mg/kg/d manganese is safe for humans needs further study. Manganese, zinc and selenium can improve oocyte quality and embryo development 61 , 62 , which is related to glycolysis 63 . Thus, the metallic compounds may improve oocyte quality by enhancing glycolysis.…”

Section: Discussionmentioning

confidence: 99%

The metallic compound promotes primordial follicle activation and ameliorates fertility deficits in aged mice

Han¹,

Huang²,

Li³

et al. 2023

Theranostics

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Background: Aged women and premature ovarian insufficiency (POI) patients have residual dormant primordial follicles that are hard to be activated through a physiological process. However, there are no effective and safe drugs to help them. Methods: We used the in vitro culture model of newborn mouse ovaries to identify the drugs that promote primordial follicle activation and study its mechanisms. It was verified by in vivo injection model of newborn mice and in vitro culture model of human ovarian tissue. In addition, we used the aged mice as a low infertility model to verify the effects of primordial follicle activation, and fertility by drugs. Results: Eleven metallic compounds activated mouse primordial follicles, and the five most effective compounds were selected for further study. Thapsigargin (TG), CrCl 3 , MnCl 2 , FeCl 3 and ZnSO 4 increased the levels of the glycolysis-related proteins (glucose transporter type 4, GLUT4; hexokinase 1, HK1; pyruvate kinase M2, PKM2; phosphofructokinase, liver type, PFKL), phosphorylated mammalian target of rapamycin (p-mTOR) in cultured mouse ovaries. The compound-promoted p-mTOR levels could be completely blocked by 2-DG (the inhibitor of glycolysis). The compounds also increased the levels of phosphorylated protein kinase B (p-Akt). TG-, CrCl 3 - and FeCl 3 -promoted p-Akt levels, but not MnCl 2 - and ZnSO 4 - promoted p-Akt levels, could be completely blocked by ISCK03 (the inhibitor of proto-oncogenic receptor tyrosine kinase, KIT). The injection of newborn mice with the compounds also activated primordial follicles and increased the levels of the glycolysis-related proteins, p-mTOR, and p-Akt. The oral administration of the compounds in adolescent and aged mice promoted primordial follicle activation, and had no obvious side effect. Importantly, ZnSO 4 also increased ovulated oocytes, oocyte quality and offspring in aged mice. Furthermore, the compounds promoted human primordial follicle activation and increased the levels of the glycolysis-related proteins, p-mTOR, and p-Akt. Conclusion: The metallic compounds activate primordial follicles through the glycolysis-dependent mTOR pathway and/or the PI3K/Akt pathway, and the oral administration of ZnSO 4 enhances fertility in aged mice. We suggest that these metallic compounds may be oral drugs to ameliorate fertility deficits in aged women and POI patients.

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Section: Discussionmentioning

confidence: 99%

The metallic compound promotes primordial follicle activation and ameliorates fertility deficits in aged mice

Han¹,

Huang²,

Li³

et al. 2023

Theranostics

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“…There are only a few studies that explored Se supplementation during IVM. One of these studies combined Se with other trace minerals (Cu, manganese, Zn) [146]. Cleavage rates were not impacted by this cocktail, but improvements in blastocyst formation, cell number, and reduced ROS concentrations were detected on day 8 blastocysts [146].…”

Section: Ivmmentioning

confidence: 99%

“…One of these studies combined Se with other trace minerals (Cu, manganese, Zn) [146]. Cleavage rates were not impacted by this cocktail, but improvements in blastocyst formation, cell number, and reduced ROS concentrations were detected on day 8 blastocysts [146]. Another study where Se was the only supplement used had improved blastocyst development with a concentration of 10 ng/mL [147].…”

Section: Ivmmentioning

confidence: 99%

An Overview of Reactive Oxygen Species Damage Occurring during In Vitro Bovine Oocyte and Embryo Development and the Efficacy of Antioxidant Use to Limit These Adverse Effects

Keane,

Ealy

2024

Animals

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The in vitro production (IVP) of bovine embryos has gained popularity worldwide and in recent years and its use for producing embryos from genetically elite heifers and cows has surpassed the use of conventional superovulation-based embryo production schemes. There are, however, several issues with the IVP of embryos that remain unresolved. One limitation of special concern is the low efficiency of the IVP of embryos. Exposure to reactive oxygen species (ROS) is one reason why the production of embryos with IVP is diminished. These highly reactive molecules are generated in small amounts through normal cellular metabolism, but their abundances increase in embryo culture because of oocyte and embryo exposure to temperature fluctuations, light exposure, pH changes, atmospheric oxygen tension, suboptimal culture media formulations, and cryopreservation. When uncontrolled, ROS produce detrimental effects on the structure and function of genomic and mitochondrial DNA, alter DNA methylation, increase lipid membrane damage, and modify protein activity. Several intrinsic enzymatic pathways control ROS abundance and damage, and antioxidants react with and reduce the reactive potential of ROS. This review will focus on exploring the efficiency of supplementing several of these antioxidant molecules on oocyte maturation, sperm viability, fertilization, and embryo culture.

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“…Therefore, Cu is considered a necessary element for reproduction and embryonic development, and Cu deficiency can alter the maturation of oocytes and their subsequent developmental ability. Several studies have been conducted on the effects of Cu supplementation during IVM in bovine oocytes and have shown that Cu has an anti-apoptotic effect on cumulus cells and improves embryonic development as well as increases glutathione levels in oocytes ( Picco et al, 2012 ; Rosa et al, 2016 ; Anchordoquy et al, 2022 ). However, the role and effects of Cu during porcine IVM have not been sufficiently studied.…”

Section: Introductionmentioning

confidence: 99%

Copper deficiency affects the developmental competence of porcine oocytes matured in vitro

Choi

Kim

et al. 2022

Front. Cell Dev. Biol.

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The trace element Cu is required for the activity of various enzymes essential for physiological processes. In this study, we elucidated the copper transport system in porcine follicular cells and investigated the effect of Cu chelation during in vitro maturation (IVM) of porcine oocytes and subsequent embryonic development after parthenogenetic activation (PA). Cu chelation was induced by adding tetraethylenepentamine (TEPA) to the maturation media (TCM199-PVA). First, we identified the localization and relative levels of the copper transporter CTR1 in follicular cells. The level of CTR1 protein was the highest in mature cumulus cells; moreover, CTR1 was mainly localized in the cytoplasmic vesicular compartment in oocytes, whereas it was evenly distributed in the cytoplasm in cumulus cells. A total of 42 h after IVM, the TEPA-treated group showed reduced maturation rates compared to those of the control (p < 0.05). This negative effect of TEPA disappeared when it was added to the media with Cu (Cu + TEPA group). The TEPA treatment during IVM significantly increased the mRNA levels of the Has2 gene, which is related to cumulus expansion (p < 0.05). Both Cu supplementation and chelation significantly increased the reactive oxygen species (ROS) levels in porcine oocytes (p < 0.05). When we analyzed the transcript levels of folliculogenesis-related genes in Cu chelation conditions, only the expression of MAPK3 in cumulus cells significantly increased compared to that of the control. We also evaluated the subsequent embryonic development of PA embryos. TEPA-treated oocytes showed significantly decreased blastocyst formation rates compared to those of the control. The TEPA-induced toxic effect was alleviated when Cu was added with TEPA. Our findings suggest that the Cu transport system plays an important role in the porcine follicular development process and that the Cu deficiency negatively affects porcine oocyte maturation, as well as their subsequent developmental competence.

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Trace mineral mixture supplemented to in vitro maturation medium improves subsequent embryo development and embryo quality in cattle

Cited by 5 publications

References 49 publications

The metallic compound promotes primordial follicle activation and ameliorates fertility deficits in aged mice

The metallic compound promotes primordial follicle activation and ameliorates fertility deficits in aged mice

An Overview of Reactive Oxygen Species Damage Occurring during In Vitro Bovine Oocyte and Embryo Development and the Efficacy of Antioxidant Use to Limit These Adverse Effects

Copper deficiency affects the developmental competence of porcine oocytes matured in vitro

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