Mutalip Siti Syairah Mohd, Rajikin Mohd Hamim, Rahim Sharaniza Ab, Khan Norashikin Mohamed Noor
1 Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Puncak Alam Campus, Selangor, Malaysia.
2 Maternofetal and Embryo Research Group (MatE), Universiti Teknologi MARA (UiTM), Malaysia.
Int J Vitam Nutr Res. 2018 Feb;88(1-2):16-26. doi: 10.1024/0300-9831/a000492. Epub 2019 Mar 20.
Protective action by annatto-derived delta-tocotrienol (δ-TCT) and soy-derived alpha-tocopherol (α-TOC) through the regulation of PI3K/Akt-Cyclin D1 pathway against the nicotine-induced DNA damages is the focus of the present study. Nicotine, which has been widely reported to have numerous adverse effects on the reproductive system, was used as reproductive toxicant. 48 female balb/c mice (6-8 weeks) (23-25 g) were randomly divided into 8 groups (G1-G8; n = 6) and treated with either nicotine or/and annatto δ-TCT/soy α-TOC for 7 consecutive days. On Day 8, the females were superovulated and mated before euthanized for embryo collection (46 hours post-coitum). Fifty 2-cell embryos from each group were used in gene expression analysis using Affymetrix QuantiGene Plex2.0 assay. Findings indicated that nicotine (G2) significantly decreased (p < 0.05) the number of produced 2-cell embryos compared to control (G1). Intervention with mixed annatto δ-TCT (G3) and pure annatto δ-TCT (G4) significantly increased the number of produced 2-cell embryos by 127 % and 79 % respectively compared to G2, but these were lower than G1. Concurrent treatment with soy α-TOC (G5) decreased embryo production by 7 %. Supplementations with δ-TCT and α-TOC alone (G6-G8) significantly increased (p < 0.05) the number of produced 2-cell embryos by 50 %, 36 % and 41 % respectively, compared to control (G1). These results were found to be associated with the alterations in the PI3K/Akt-Cyclin D1 gene expressions, indicating the inhibitory effects of annatto δ-TCT and soy α-TOC against the nicotinic embryonic damages. To our knowledge, this is the first attempt on studying the benefits of annatto δ-TCT on murine preimplantation 2-cell embryos.
本研究的重点是探讨来自胭脂树的δ-生育三烯酚(δ-TCT)和来自大豆的α-生育酚(α-TOC)通过调节PI3K/Akt-细胞周期蛋白D1途径对尼古丁诱导的DNA损伤的保护作用。尼古丁对生殖系统有诸多不良影响,已被广泛报道,本研究将其用作生殖毒性物质。48只6-8周龄(23-25克)的雌性balb/c小鼠被随机分为8组(G1-G8;每组n = 6),连续7天用尼古丁或/和胭脂树δ-TCT/大豆α-TOC进行处理。在第8天,雌性小鼠进行超排卵并交配,然后在安乐死后收集胚胎(交配后46小时)。每组选取50个2细胞胚胎,使用Affymetrix QuantiGene Plex2.0检测法进行基因表达分析。研究结果表明,与对照组(G1)相比,尼古丁组(G2)产生的2细胞胚胎数量显著减少(p < 0.05)。与G2组相比,混合胭脂树δ-TCT组(G3)和纯胭脂树δ-TCT组(G4)产生的2细胞胚胎数量分别显著增加了127%和79%,但仍低于G1组。大豆α-TOC联合处理组(G5)胚胎产量降低了7%。与对照组(G1)相比,单独补充δ-TCT和α-TOC组(G6-G8)产生的2细胞胚胎数量分别显著增加了50%、36%和41%(p < 0.05)。这些结果与PI3K/Akt-细胞周期蛋白D1基因表达的变化有关,表明胭脂树δ-TCT和大豆α-TOC对尼古丁引起的胚胎损伤具有抑制作用。据我们所知,这是首次研究胭脂树δ-TCT对小鼠植入前2细胞胚胎益处的尝试。