Ovarian aging has been associated with oxidative stress and loss of ovarian function. Tocotrienol has been proven to exert beneficial effects on the female reproductive system. However, the role of tocotrienol in affecting metabolism in the ovary and subsequently improving the quality of oocytes in aging mice remains unknown. Therefore, the relationship between metabolic changes in the ovary and the quality of oocytes in aging mice following tocotrienol-rich fraction (TRF) supplementation was investigated. Six-week-old female mice were used as the Young group. Six-month-old aged female mice were divided into four groups; the first group was given tocopherol-stripped corn oil (vehicle control) while the other three groups were supplemented with TRF at the dose of 90, 120, and 150 mg/kg, respectively. The treatment was given orally for two months. At the end of the treatment, mice from all groups were superovulated and then euthanised. Oocyte quality was assessed and non-targeted metabolomic analysis of the ovarian tissues was performed using liquid chromatography-tandem mass spectrometry of quadrupole time-of-flight (LC-MS Q-TOF). Percentages of normal oocytes were higher (p<0.001) while abnormal oocytes were lower (p<0.001) in TRF 150 mg/kg group compared to that of the control. Seventeen metabolites were identified to be significantly different in the ovarian tissue of the aging group when compared to the young group. 14 metabolites were identified to be significantly different in the ovarian tissue between the control and TRF supplemented groups. Pathway analysis revealed significantly altered metabolic pathways for fatty acid and amino acid metabolism that might influence the quality of oocytes. In conclusion, TRF supplementation causes metabolic changes in the ovary that delay the consequences of aging, thus improving the quality of oocytes in aging mice.
The Effect of Tocotrienol-Rich Fraction Supplementation on the Ovarian Metabolome and the Quality of Oocyte in Aging Mice
Abstrak
Penuaan ovari telah dikaitkan dengan tekanan oksidatif dan kehilangan fungsi ovari. Tokotrienol telah dibuktikan dapat memberi kesan yang baik terhadap sistem pembiakan wanita. Walau bagaimanapun, peranan tokotrienol ke atas metabolisma ovari dan seterusnya peningkatan kualiti oosit dalam mencit tua masih tidak diketahui. Oleh itu, hubungan antara perubahan aktiviti metabolik dalam ovari dan kualiti oosit dalam mencit tua selepas suplementasi fraksi kaya tokotrienol (TRF) telah dikaji. Mencit betina berusia enam minggu digunakan sebagai kumpulan Muda. Mencit betina berusia enam bulan dibahagikan kepada empat kumpulan iaitu kumpulan pertama yang diberikan minyak jagung-bebas tokoferol (kawalan) manakala tiga kumpulan yang lain diberi suplimen TRF pada dos 90, 120, dan 150 mg/kg. Rawatan diberikan secara oral selama dua bulan. Pada akhir rawatan, mencit dari semua kumpulan disuperovulasi dan kemudian dikorbankan. Kualiti oosit dinilai dan analisis metabolomik secara tidak disasarkan, pada tisu ovari dijalankan dengan menggunakan 'liquid chromatography tandem mass spectrometry of quadrupole time-of-flight' (LC-MS Q-TOF). Peratusan oosit normal adalah lebih tinggi (p<0.001) manakala peratusan oosit yang tidak normal adalah lebih rendah (p<0.001) dalam kumpulan terawat dengan 150 mg/kg TRF berbanding dengan kawalan. Sebanyak 17 metabolit telah dikenal pasti menunjukkan perbezaan yang nyata dalam tisu ovari kumpulan Penuaan secara berbanding dengan kumpulan Muda. Selain itu, terdapat 14 metabolit yang menunjukkan perbezaan yang nyata antara kumpulan terawat TRF dengan kumpulan kawalan. Analisa tapak jalan menunjukkan perubahan tapak jalan metabolik dalam metabolisma asid lemak dan asid amino yang nyata berkemungkinan dapat mempengaruhi kualiti oosit. Kesimpulannya, suplementasi TRF dapat mengaruh perubahan metabolik dalam ovari yang dapat melambatkan kesan penuaan dan seterusnya meningkatkan kualiti oosit di dalam mencit tua.
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