PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos
Extensive mitochondrial replication during oogenesis and its role in oocyte maturation and fertilization indicate that the amount of mitochondrial DNA (mtDNA) may play a significant role in early embryonic development. Early embryos express peroxisome proliferator-activated receptor gamma co-activat...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1531378/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841525888965935104 |
|---|---|
| author | Muhammad Idrees Muhammad Idrees Zaheer Haider Chalani Dilshani Perera Safeer Ullah Seo-Hyeon Lee Seung Eun Lee Sung-Sik Kang Sung Woo Kim Il-Keun Kong Il-Keun Kong Il-Keun Kong |
| author_facet | Muhammad Idrees Muhammad Idrees Zaheer Haider Chalani Dilshani Perera Safeer Ullah Seo-Hyeon Lee Seung Eun Lee Sung-Sik Kang Sung Woo Kim Il-Keun Kong Il-Keun Kong Il-Keun Kong |
| author_sort | Muhammad Idrees |
| collection | DOAJ |
| description | Extensive mitochondrial replication during oogenesis and its role in oocyte maturation and fertilization indicate that the amount of mitochondrial DNA (mtDNA) may play a significant role in early embryonic development. Early embryos express peroxisome proliferator-activated receptor gamma co-activator alpha (PPARGC1A/PGC-1a), a protein essential for mitochondrial biogenesis. This study investigated the role of PGC-1α from a single-cell zygotic stage to day-8 bovine blastocyst and the effect of PGC-1a knockdown (KD) on embryo mitochondria and development. PGC-1α KD via siRNA injection into single-cell zygotes does not substantially affect embryonic cleavage up to the morula stage but considerably reduces blastocyst development (18.42%) and hatching than the control (32.81%). PGC-1α regulates transcription of the gene encoding mitochondrial transcription factor A (TFAM), and immunofluorescence analysis indicated significantly lower TFAM expression in the 16-cell KD embryos and day-8 KD blastocysts. Reduction in NRF1 protein’s nuclear localization in bovine blastomeres was also observed in PGC-1α-KD embryos. Furthermore, to understand the effect of PGC-1α-KD on the mitochondrial genome, we found a low mtDNA copy number in PGC-1α-KD day-8 bovine blastocysts. Several genes related to mitochondrial functioning, like ND1, ND3, ND5, ATPase8, COI, COII, and CYTB, were significantly downregulated in PGC-1α-KD embryos. Moreover, high mitochondrial depolarization (ΔΨm) and abnormal lipid depositions were observed in the PGC-1α KD blastocysts. SIRT1 is the upstream regulator of PGC-1α, but SIRT1 activation via Hesperetin does not affect PGC-1α-KD embryonic development considerably. In conclusion, PGC-1α plays a critical role in early embryo mitochondrial functioning, and any perturbation in its expression significantly disrupts early embryonic development. |
| format | Article |
| id | doaj-art-e1822a0790e142da85169fdf78542957 |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-e1822a0790e142da85169fdf785429572025-01-17T06:51:12ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011210.3389/fcell.2024.15313781531378PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryosMuhammad Idrees0Muhammad Idrees1Zaheer Haider2Chalani Dilshani Perera3Safeer Ullah4Seo-Hyeon Lee5Seung Eun Lee6Sung-Sik Kang7Sung Woo Kim8Il-Keun Kong9Il-Keun Kong10Il-Keun Kong11Department of Animal Science, Division of Applied Life Science (BK21 Four Program), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaInstitute of Agriculture and Life Science (IALS), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDepartment of Animal Science, Division of Applied Life Science (BK21 Four Program), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDepartment of Animal Science, Division of Applied Life Science (BK21 Four Program), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDepartment of Animal Science, Division of Applied Life Science (BK21 Four Program), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDepartment of Animal Science, Division of Applied Life Science (BK21 Four Program), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaDepartment of Animal Science, Division of Applied Life Science (BK21 Four Program), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaHanwoo Research Institute, National Institute of Animal Science, Rural Development Administration, Gangwon, Republic of KoreaHanwoo Research Institute, National Institute of Animal Science, Rural Development Administration, Gangwon, Republic of KoreaDepartment of Animal Science, Division of Applied Life Science (BK21 Four Program), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaInstitute of Agriculture and Life Science (IALS), Gyeongsang National University, Jinju, Gyeongnam, Republic of KoreaThe King Kong Corp. Ltd., Gyeongsang National University, Jinju-si, Gyeongnam, Republic of KoreaExtensive mitochondrial replication during oogenesis and its role in oocyte maturation and fertilization indicate that the amount of mitochondrial DNA (mtDNA) may play a significant role in early embryonic development. Early embryos express peroxisome proliferator-activated receptor gamma co-activator alpha (PPARGC1A/PGC-1a), a protein essential for mitochondrial biogenesis. This study investigated the role of PGC-1α from a single-cell zygotic stage to day-8 bovine blastocyst and the effect of PGC-1a knockdown (KD) on embryo mitochondria and development. PGC-1α KD via siRNA injection into single-cell zygotes does not substantially affect embryonic cleavage up to the morula stage but considerably reduces blastocyst development (18.42%) and hatching than the control (32.81%). PGC-1α regulates transcription of the gene encoding mitochondrial transcription factor A (TFAM), and immunofluorescence analysis indicated significantly lower TFAM expression in the 16-cell KD embryos and day-8 KD blastocysts. Reduction in NRF1 protein’s nuclear localization in bovine blastomeres was also observed in PGC-1α-KD embryos. Furthermore, to understand the effect of PGC-1α-KD on the mitochondrial genome, we found a low mtDNA copy number in PGC-1α-KD day-8 bovine blastocysts. Several genes related to mitochondrial functioning, like ND1, ND3, ND5, ATPase8, COI, COII, and CYTB, were significantly downregulated in PGC-1α-KD embryos. Moreover, high mitochondrial depolarization (ΔΨm) and abnormal lipid depositions were observed in the PGC-1α KD blastocysts. SIRT1 is the upstream regulator of PGC-1α, but SIRT1 activation via Hesperetin does not affect PGC-1α-KD embryonic development considerably. In conclusion, PGC-1α plays a critical role in early embryo mitochondrial functioning, and any perturbation in its expression significantly disrupts early embryonic development.https://www.frontiersin.org/articles/10.3389/fcell.2024.1531378/fullPGC-1αmitochondrial DNATFAMNRFbovine blastocyst |
| spellingShingle | Muhammad Idrees Muhammad Idrees Zaheer Haider Chalani Dilshani Perera Safeer Ullah Seo-Hyeon Lee Seung Eun Lee Sung-Sik Kang Sung Woo Kim Il-Keun Kong Il-Keun Kong Il-Keun Kong PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos Frontiers in Cell and Developmental Biology PGC-1α mitochondrial DNA TFAM NRF bovine blastocyst |
| title | PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos |
| title_full | PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos |
| title_fullStr | PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos |
| title_full_unstemmed | PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos |
| title_short | PPARGC1A regulates transcriptional control of mitochondrial biogenesis in early bovine embryos |
| title_sort | ppargc1a regulates transcriptional control of mitochondrial biogenesis in early bovine embryos |
| topic | PGC-1α mitochondrial DNA TFAM NRF bovine blastocyst |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1531378/full |
| work_keys_str_mv | AT muhammadidrees ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT muhammadidrees ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT zaheerhaider ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT chalanidilshaniperera ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT safeerullah ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT seohyeonlee ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT seungeunlee ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT sungsikkang ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT sungwookim ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT ilkeunkong ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT ilkeunkong ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos AT ilkeunkong ppargc1aregulatestranscriptionalcontrolofmitochondrialbiogenesisinearlybovineembryos |