Yuan Shuiqiao, Ortogero Nicole, Wu Qiuxia, Zheng Huili, Yan Wei
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
Biol Reprod. 2014 Aug;91(2):39. doi: 10.1095/biolreprod.114.119370. Epub 2014 Jul 2.
Both DICER and DROSHA are RNase III enzymes involved in the biogenesis of small noncoding RNAs. DROSHA cleaves the stem-loop portion of the primary miRNAs and produces precursor miRNAs in the nucleus, whereas DICER processes double-stranded RNA precursors into mature miRNAs and endogenous small interference RNAs in the cytoplasm. Selective inactivation of Dicer in growing oocytes of primary follicles leads to female infertility due to oocyte spindle defects. However, it remains unknown if oocyte Dicer expression in the fetal ovary is required for proper follicular development in the postnatal ovary. Moreover, the role of Drosha in folliculogenesis has never been investigated. Here, we report that conditional knockout of Dicer in prophase I oocytes of the fetal ovary led to compromised folliculogenesis, premature ovarian failure, and female infertility in the adult ovary, whereas selective inactivation of Drosha in oocytes of either the fetal or the developing ovary had no effects on normal folliculogenesis and female fertility in adulthood. Our data indicate that oocyte DICER expression in the fetal ovary is required, and oocyte DROSHA is dispensable, for postnatal follicular development and female fertility in adulthood.
DICER和DROSHA都是参与小非编码RNA生物合成的RNase III酶。DROSHA切割初级微小RNA(pri-miRNAs)的茎环部分,并在细胞核中产生前体微小RNA(pre-miRNAs),而DICER则将双链RNA前体加工成成熟的微小RNA和细胞质中的内源性小干扰RNA。在初级卵泡的生长卵母细胞中选择性失活Dicer会由于卵母细胞纺锤体缺陷导致雌性不育。然而,尚不清楚胎儿卵巢中的卵母细胞Dicer表达对于出生后卵巢的正常卵泡发育是否是必需的。此外,Drosha在卵泡发生中的作用从未被研究过。在这里,我们报告说,胎儿卵巢减数分裂前期I卵母细胞中Dicer的条件性敲除导致卵泡发生受损、卵巢早衰和成年卵巢中的雌性不育,而在胎儿或发育中的卵巢的卵母细胞中选择性失活Drosha对成年期的正常卵泡发生和雌性生育力没有影响。我们的数据表明胎儿卵巢中的卵母细胞DICER表达对于出生后卵泡发育和成年期雌性生育力是必需的,而卵母细胞DROSHA是可有可无的。