Paredes Alfonso, Garcia-Rudaz Cecilia, Kerr Bredford, Tapia Veronica, Dissen Gregory A, Costa Maria E, Cornea Anda, Ojeda Sergio R
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, 97006, USA.
Endocrinology. 2005 Dec;146(12):5267-77. doi: 10.1210/en.2005-0965. Epub 2005 Sep 8.
In the rat ovary, germ and somatic cells become organized into primordial follicles 48-72 h after birth. Although several genes have been implicated in the control of early follicular growth, less is known about the factors involved in the formation of primordial follicles. Using the method of differential display of mRNAs, we found several genes differentially expressed at the time of follicular assembly. One of them encodes synaptonemal complex protein-1 (SCP1), a core component of the protein complex that maintains recombining chromosomes together during prophase I of the first meiotic division in germ cells. This association, evident during the pachytene stage, ends when chromosomal desynapsis begins in the diplotene stage at the end of prophase I. Oocytes become arrested in the diplotene/dictate stage before becoming enclosed into primordial follicles, suggesting that oocytes must complete meiotic prophase I before becoming competent to direct follicle assembly. We now show that attainment of the diplotene stage results in follicular formation. In developing rat ovaries, SCP1 mRNA expression is confined to oocytes and decreases precipitously within 24 h after birth, preceding the organization of primordial follicles. The premature loss of SCP1, achieved via treatment with an antisense oligodeoxynucleotide targeting SCP1 mRNA, resulted in more oocytes reaching the diplotene stage, as evidenced by a decrease in the number of oocytes containing germ cell nuclear antigen-1 (a nuclear protein whose expression ceases in diplotene) and an increase in the number of oocytes expressing MSY2 (a cytoplasmic Y box protein expressed in oocytes that have become arrested in diplotene). SCP1-deficient ovaries exhibited an increased number of newly formed follicles, suggesting that completion of meiotic prophase I endows oocytes with the ability to orchestrate follicular assembly.
在大鼠卵巢中，生殖细胞和体细胞在出生后48 - 72小时组织形成原始卵泡。尽管已有多个基因参与早期卵泡生长的调控，但对于原始卵泡形成所涉及的因素却知之甚少。利用mRNA差异显示方法，我们发现了几个在卵泡组装时差异表达的基因。其中一个基因编码联会复合体蛋白-1（SCP1），它是在生殖细胞第一次减数分裂前期I将重组染色体维系在一起的蛋白质复合体的核心成分。这种在粗线期明显的关联，在前期I末期双线期染色体解联会开始时结束。卵母细胞在被包裹进原始卵泡之前停滞于双线期/核仁期，这表明卵母细胞在具备指导卵泡组装能力之前必须完成减数分裂前期I。我们现在表明，达到双线期会导致卵泡形成。在发育中的大鼠卵巢中，SCP1 mRNA表达局限于卵母细胞，且在出生后24小时内急剧下降，早于原始卵泡的组织形成。通过用靶向SCP1 mRNA的反义寡脱氧核苷酸处理实现SCP1的过早缺失，导致更多卵母细胞达到双线期，这可通过含有生殖细胞核抗原-1（一种在双线期表达停止的核蛋白）的卵母细胞数量减少以及表达MSY2（一种在停滞于双线期的卵母细胞中表达的细胞质Y盒蛋白）的卵母细胞数量增加得以证明。SCP1缺陷型卵巢中新形成的卵泡数量增加，这表明减数分裂前期I的完成赋予卵母细胞协调卵泡组装的能力。
