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Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos

Age-associated decline in oocyte quality is one of the dominant factors of low fertility. Aging alters several key processes, such as telomere lengthening, cell senescence, and cellular longevity of granulosa cells surrounding oocyte. To investigate the age-dependent molecular changes, we examined t...

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Autores principales: Xu, Lianguang, Idrees, Muhammad, Joo, Myeong-Don, Sidrat, Tabinda, Wei, Yiran, Song, Seok-Hwan, Lee, Kyeong-Lim, Kong, Il-Keun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158768/
https://www.ncbi.nlm.nih.gov/pubmed/34070219
http://dx.doi.org/10.3390/ijms22105327
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author Xu, Lianguang
Idrees, Muhammad
Joo, Myeong-Don
Sidrat, Tabinda
Wei, Yiran
Song, Seok-Hwan
Lee, Kyeong-Lim
Kong, Il-Keun
author_facet Xu, Lianguang
Idrees, Muhammad
Joo, Myeong-Don
Sidrat, Tabinda
Wei, Yiran
Song, Seok-Hwan
Lee, Kyeong-Lim
Kong, Il-Keun
author_sort Xu, Lianguang
collection PubMed
description Age-associated decline in oocyte quality is one of the dominant factors of low fertility. Aging alters several key processes, such as telomere lengthening, cell senescence, and cellular longevity of granulosa cells surrounding oocyte. To investigate the age-dependent molecular changes, we examined the expression, localization, and correlation of telomerase reverse transcriptase (TERT) and β-Klotho (KLB) in bovine granulosa cells, oocytes, and early embryos during the aging process. Herein, cumulus-oocyte complexes (COCs) obtained from aged cows (>120 months) via ovum pick-up (OPU) showed reduced expression of β-Klotho and its co-receptor fibroblast growth factor receptor 1 (FGFR1). TERT plasmid injection into pronuclear zygotes not only markedly enhanced day-8 blastocysts’ development competence (39.1 ± 0.8%) compared to the control (31.1 ± 0.5%) and D-galactose (17.9 ± 1.0%) treatment groups but also enhanced KLB and FGFR1 expression. In addition, plasmid-injected zygotes displayed a considerable enhancement in blastocyst quality and implantation potential. Cycloastragenol (CAG), an extract of saponins, stimulates telomerase enzymes and enhances KLB expression and alleviates age-related deterioration in cultured primary bovine granulosa cells. In conclusion, telomerase activation or constitutive expression will increase KLB expression and activate the FGFR1/β-Klotho pathway in bovine granulosa cells and early embryos, inhibiting age-related malfunctioning.
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spelling pubmed-81587682021-05-28 Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos Xu, Lianguang Idrees, Muhammad Joo, Myeong-Don Sidrat, Tabinda Wei, Yiran Song, Seok-Hwan Lee, Kyeong-Lim Kong, Il-Keun Int J Mol Sci Article Age-associated decline in oocyte quality is one of the dominant factors of low fertility. Aging alters several key processes, such as telomere lengthening, cell senescence, and cellular longevity of granulosa cells surrounding oocyte. To investigate the age-dependent molecular changes, we examined the expression, localization, and correlation of telomerase reverse transcriptase (TERT) and β-Klotho (KLB) in bovine granulosa cells, oocytes, and early embryos during the aging process. Herein, cumulus-oocyte complexes (COCs) obtained from aged cows (>120 months) via ovum pick-up (OPU) showed reduced expression of β-Klotho and its co-receptor fibroblast growth factor receptor 1 (FGFR1). TERT plasmid injection into pronuclear zygotes not only markedly enhanced day-8 blastocysts’ development competence (39.1 ± 0.8%) compared to the control (31.1 ± 0.5%) and D-galactose (17.9 ± 1.0%) treatment groups but also enhanced KLB and FGFR1 expression. In addition, plasmid-injected zygotes displayed a considerable enhancement in blastocyst quality and implantation potential. Cycloastragenol (CAG), an extract of saponins, stimulates telomerase enzymes and enhances KLB expression and alleviates age-related deterioration in cultured primary bovine granulosa cells. In conclusion, telomerase activation or constitutive expression will increase KLB expression and activate the FGFR1/β-Klotho pathway in bovine granulosa cells and early embryos, inhibiting age-related malfunctioning. MDPI 2021-05-18 /pmc/articles/PMC8158768/ /pubmed/34070219 http://dx.doi.org/10.3390/ijms22105327 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Lianguang
Idrees, Muhammad
Joo, Myeong-Don
Sidrat, Tabinda
Wei, Yiran
Song, Seok-Hwan
Lee, Kyeong-Lim
Kong, Il-Keun
Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos
title Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos
title_full Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos
title_fullStr Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos
title_full_unstemmed Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos
title_short Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos
title_sort constitutive expression of tert enhances β-klotho expression and improves age-related deterioration in early bovine embryos
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158768/
https://www.ncbi.nlm.nih.gov/pubmed/34070219
http://dx.doi.org/10.3390/ijms22105327
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