Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryos
Somatic cell nuclear transfer (SCNT) is important in assisted reproductive technologies. However, its reprogramming efficiency remains low. A considerable drawback of SCNT-cloned embryos is the reduction in telomerase activity, which is crucial for DNA stability and genetic and epigenetic reprogramm...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1628953/full |
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| author | Zaheer Haider Safeer Ullah Tahir Muhammad Chalani Dilshani Perera Muhammad Tayyab Khan Asif Jan Seung-Eun Lee Seo-Hyun Lee Sung Woo Kim Muhammad Idrees Muhammad Idrees Il-Keun Kong Il-Keun Kong Il-Keun Kong |
| author_facet | Zaheer Haider Safeer Ullah Tahir Muhammad Chalani Dilshani Perera Muhammad Tayyab Khan Asif Jan Seung-Eun Lee Seo-Hyun Lee Sung Woo Kim Muhammad Idrees Muhammad Idrees Il-Keun Kong Il-Keun Kong Il-Keun Kong |
| author_sort | Zaheer Haider |
| collection | DOAJ |
| description | Somatic cell nuclear transfer (SCNT) is important in assisted reproductive technologies. However, its reprogramming efficiency remains low. A considerable drawback of SCNT-cloned embryos is the reduction in telomerase activity, which is crucial for DNA stability and genetic and epigenetic reprogramming. The present study aimed to examine the effects of madecassic acid (MA), a potent telomerase activator, on the developmental rate, embryonic genome activation, and implantation potential of SCNT-derived bovine embryos. The treatment of bovine signal cell-cloned zygotes with 3.0 μg/mL MA significantly increased embryo cleavage (71.5%) and blastocyst rate (28.1%) compared with that in non-treated (control) SCNT-cloned bovine embryos. In addition, MA treatment enhanced the bovine granulosa cells' telomerase activity and telomerase expression are assessed using qTRAP assay and ELISA. Of note, MA enhanced the expression of embryonic genome activation (EGA)-related genes including NFYA, SP1, DPRX, GSC, CTNNB1, DUX, and ARGFX in MA-treated cloned embryos compared to the control group. Moreover, MA-treatment of cloned embryos showed substantially less DNA damage than the control SCNT embryos. Mechanistically, MA activation of telomerase reverse transcriptase (TERT) significantly enhanced the nuclear localization of β-catenin and c-Myc and improved EGA. Reduction in the nuclear localization of this triose may be the leading cause of reduced EGA in cloned embryos. In conclusion, MA impacted the EGA reprogramming and development of cloned bovine embryos via probable activation of TERT. This telomerase activator may have the application of improving SCNT-cloned bovine embryos. |
| format | Article |
| id | doaj-art-329a10047d7a4f2dbcd470f77278e66f |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-329a10047d7a4f2dbcd470f77278e66f2025-08-20T03:28:24ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-07-011310.3389/fcell.2025.16289531628953Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryosZaheer Haider0Safeer Ullah1Tahir Muhammad2Chalani Dilshani Perera3Muhammad Tayyab Khan4Asif Jan5Seung-Eun Lee6Seo-Hyun Lee7Sung Woo Kim8Muhammad Idrees9Muhammad Idrees10Il-Keun Kong11Il-Keun Kong12Il-Keun Kong13Division of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaMolecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Institute of Medical Science, University of Toronto, Toronto, ON, CanadaDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDepartment of Pharmacy, University of Peshawar, Peshawar, PakistanDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaHanwoo Research Institute, National Institute of Animal Science, Rural Development Administration, Pyeongchang, Gangwon, Republic of KoreaDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaInstitute of Agriculture and Life Science, Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaInstitute of Agriculture and Life Science, Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaTheKingKong Corp. Ltd., Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaSomatic cell nuclear transfer (SCNT) is important in assisted reproductive technologies. However, its reprogramming efficiency remains low. A considerable drawback of SCNT-cloned embryos is the reduction in telomerase activity, which is crucial for DNA stability and genetic and epigenetic reprogramming. The present study aimed to examine the effects of madecassic acid (MA), a potent telomerase activator, on the developmental rate, embryonic genome activation, and implantation potential of SCNT-derived bovine embryos. The treatment of bovine signal cell-cloned zygotes with 3.0 μg/mL MA significantly increased embryo cleavage (71.5%) and blastocyst rate (28.1%) compared with that in non-treated (control) SCNT-cloned bovine embryos. In addition, MA treatment enhanced the bovine granulosa cells' telomerase activity and telomerase expression are assessed using qTRAP assay and ELISA. Of note, MA enhanced the expression of embryonic genome activation (EGA)-related genes including NFYA, SP1, DPRX, GSC, CTNNB1, DUX, and ARGFX in MA-treated cloned embryos compared to the control group. Moreover, MA-treatment of cloned embryos showed substantially less DNA damage than the control SCNT embryos. Mechanistically, MA activation of telomerase reverse transcriptase (TERT) significantly enhanced the nuclear localization of β-catenin and c-Myc and improved EGA. Reduction in the nuclear localization of this triose may be the leading cause of reduced EGA in cloned embryos. In conclusion, MA impacted the EGA reprogramming and development of cloned bovine embryos via probable activation of TERT. This telomerase activator may have the application of improving SCNT-cloned bovine embryos.https://www.frontiersin.org/articles/10.3389/fcell.2025.1628953/fullSCNTarttelomerasein vitro embryo production (IVP)madecassic acid (MA) |
| spellingShingle | Zaheer Haider Safeer Ullah Tahir Muhammad Chalani Dilshani Perera Muhammad Tayyab Khan Asif Jan Seung-Eun Lee Seo-Hyun Lee Sung Woo Kim Muhammad Idrees Muhammad Idrees Il-Keun Kong Il-Keun Kong Il-Keun Kong Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryos Frontiers in Cell and Developmental Biology SCNT art telomerase in vitro embryo production (IVP) madecassic acid (MA) |
| title | Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryos |
| title_full | Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryos |
| title_fullStr | Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryos |
| title_full_unstemmed | Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryos |
| title_short | Activation of telomerase via madecassic acid enhances the developmental competence of the SCNT-derived bovine embryos |
| title_sort | activation of telomerase via madecassic acid enhances the developmental competence of the scnt derived bovine embryos |
| topic | SCNT art telomerase in vitro embryo production (IVP) madecassic acid (MA) |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1628953/full |
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