Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, West Campus, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Biol Reprod. 2010 Jun;82(6):1190-7. doi: 10.1095/biolreprod.109.081984. Epub 2010 Mar 3.
WEE1 homolog 2 (WEE2, also known as WEE1B) is a newly identified member of the WEE kinase family that is conserved from yeast to humans. The aim of the present study was to determine the spatiotemporal expression pattern and the function of WEE2 during oocyte maturation in a nonhuman primate species, the rhesus macaque. Among 11 macaque tissues examined, WEE2 transcript is predominantly expressed in the ovary and only weakly detectable in the testis. Within the ovary, WEE2 mRNA is exclusively localized in the oocyte and appears to accumulate during folliculogenesis, reaching the highest level in preovulatory follicles. Microinjection of a full-length WEE2-GFP (green fluorescent protein) fusion mRNA indicates a specific nuclear localization of WEE2 protein in both growing and fully grown germinal vesicle (GV)-intact oocytes. Taking the long double-stranded RNA-mediated RNA interference approach, we found that down-regulation of WEE2 led to meiotic resumption in a subset of GV oocytes even in the presence of a phosphodiesterase 3 inhibitor. On the other hand, overexpression of WEE2 delays the reentry of oocytes into meiosis in both mice and monkeys. These findings suggest that WEE2 is a conserved oocyte-specific meiosis inhibitor that functions downstream of cAMP in nonhuman primates.
WEE1 同源物 2(WEE2,也称为 WEE1B)是 WEE 激酶家族的新成员,从酵母到人类都有保守序列。本研究旨在确定 WEE2 在非人类灵长类动物(猕猴)卵母细胞成熟过程中的时空表达模式和功能。在检测的 11 种猕猴组织中,WEE2 转录本主要在卵巢中表达,在睾丸中仅弱表达。在卵巢中,WEE2mRNA 仅在卵母细胞中特异性定位,并在卵泡发生过程中积累,在排卵前卵泡中达到最高水平。全长 WEE2-GFP(绿色荧光蛋白)融合 mRNA 的显微注射表明,WEE2 蛋白在生长和完全成熟的生发泡(GV)完整卵母细胞中具有特异性核定位。采用长双链 RNA 介导的 RNA 干扰方法,我们发现即使存在磷酸二酯酶 3 抑制剂,下调 WEE2 也会导致部分 GV 卵母细胞恢复减数分裂。另一方面,WEE2 的过表达会延迟小鼠和猴子卵母细胞重新进入减数分裂。这些发现表明,WEE2 是一种保守的卵母细胞特异性减数分裂抑制剂,在非人类灵长类动物中作用于 cAMP 下游。