Saadeldin Islam M, Swelum Ayman Abdel-Aziz, Elsafadi Mona, Mahmood Amer, Yaqoob Syed Hilal, Alfayez Musaad, Alowaimer Abdullah N
Department of Animal Production, College of Food and Agricultural Sciences, King Saud University, 11451 Riyadh, Kingdom of Saudi Arabia.
Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt.
J Reprod Dev. 2019 Jun 14;65(3):215-221. doi: 10.1262/jrd.2018-073. Epub 2019 Feb 14.
All-trans retinoic acid (RA) is a metabolite of vitamin A and has pleiotropic actions on many different biological processes, including cell growth and differentiation, and is involved in different aspects of fertility and developmental biology. In the current study, we investigated the effects of RA on camel (Camelus dromedarius) cumulus-oocyte complex in vitro maturation (IVM). IVM medium was supplemented with 0, 10, 20, and 40 µM RA. Application of 20 µM RA significantly reduced the proportion of degenerated oocytes and significantly improved oocyte meiosis and first polar body extrusion compared to the control and other experimental groups. Retinoic acid significantly reduced the mRNA transcript levels of apoptosis-related genes, including BAX and P53, and reduced the BAX/BCL2 ratio. In addition, RA significantly reduced the expression of the Transforming growth factor beta (TGFβ) pathway-related transcripts associated with the actin cytoskeleton, ACTA2 and TAGLN; however, RA increased TGFβ expression in cumulus cells. The small molecule SB-431542 inhibits the TGFβ pathway by inhibiting the activity of activin receptor-like kinases (ALK-4, ALK-5, and ALK-7); however, combined supplementation with RA during IVM compensated for the inhibitory effect of SB-431542 on cumulus expansion, oocyte meiosis I, and first polar body extrusion in activated oocytes. The current study shows the beneficial effects of RA on camel oocyte IVM and provides a model to study the multifunctional mechanisms involved in cumulus expansion and oocyte meiosis, particularly those involved in the TGFβ pathway.
全反式维甲酸（RA）是维生素A的一种代谢产物，对许多不同的生物学过程具有多效性作用，包括细胞生长和分化，并且参与生育和发育生物学的不同方面。在本研究中，我们调查了RA对骆驼（单峰驼）卵丘-卵母细胞复合体体外成熟（IVM）的影响。IVM培养基中添加了0、10、20和40μM的RA。与对照组和其他实验组相比，添加20μM的RA显著降低了退化卵母细胞的比例，并显著改善了卵母细胞减数分裂和第一极体排出。维甲酸显著降低了凋亡相关基因（包括BAX和P53）的mRNA转录水平，并降低了BAX/BCL2比值。此外，RA显著降低了与肌动蛋白细胞骨架相关的转化生长因子β（TGFβ）途径相关转录本ACTA2和TAGLN的表达；然而，RA增加了卵丘细胞中TGFβ的表达。小分子SB-431542通过抑制激活素受体样激酶（ALK-4、ALK-5和ALK-7）的活性来抑制TGFβ途径；然而，在IVM期间与RA联合补充可补偿SB-431542对卵丘扩展、卵母细胞减数分裂I以及激活卵母细胞中第一极体排出的抑制作用。本研究显示了RA对骆驼卵母细胞IVM的有益作用，并提供了一个模型来研究参与卵丘扩展和卵母细胞减数分裂的多功能机制，特别是那些参与TGFβ途径的机制。
