GATA-like protein-1 (GLP-1) is required for normal germ cell development during embryonic oogenesis.

GATA-like protein-1 (GLP-1) is required for normal germ cell development during embryonic oogenesis.
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DOI:
10.1530/rep-10-0376
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发表时间:
2011-02
期刊:
影响因子:
3.8
通讯作者:
Tamara J. Strauss;D. Castrillon;S. Hammes
Tamara J. Strauss;D. Castrillon;S. Hammes
中科院分区:
生物学3区
文献类型:
--
作者:
Tamara J. Strauss;D. Castrillon;S. Hammes

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卵子发生和原始卵泡形成是紧密相连的过程,需要体细胞和生殖细胞之间有组织和精确定时的通信。卵巢细胞串扰的偏差,或细胞群之一内的异常基因表达,可导致卵泡丢失或功能障碍,从而导致不育。GATA样蛋白-1(GLP-1)在卵巢体细胞中的表达是雌性小鼠正常生育所必需的,因为GLP-1缺乏导致出生时缺乏卵母细胞。然而,这种生殖细胞损失的时间和性质还不清楚。在这项研究中,我们描述了GLP-1基因敲除小鼠的胚胎生殖细胞损失。定量PCR显示卵巢Glp-1 mRNA在胚胎发生过程中以双峰模式表达,在E13.5-14.5达到峰值,在出生时再次达到峰值。相反,成年卵巢表达低但可检测水平的Glp-1 mRNA。对发育中的GLP-1缺失小鼠卵巢的分析表明,生殖细胞被适当指定并正常迁移至新生性腺。到达性腺后,生殖细胞的早熟损失开始于E13.5左右。这种丧失在出生时完成,并伴随着与减数分裂进入相关的基因表达缺陷。有趣的是,体细胞前颗粒细胞仍然形成围绕生殖系囊肿的基底膜,并表达编码与卵母细胞沟通的旁分泌信号分子的mRNA,尽管水平低于正常水平。总之,这些数据意味着体细胞蛋白GLP-1不是许多前颗粒细胞功能所必需的,而是生殖细胞存活所必需的。
Oogenesis and primordial follicle formation are tightly linked processes, requiring organized and precisely timed communication between somatic and germ cells. Deviations in ovarian cell cross talk, or aberrant gene expression within one of the cell populations, can lead to follicle loss or dysfunction, resulting in infertility. Expression of GATA-like protein-1 (GLP-1) in ovarian somatic cells is required for normal fertility in female mice, as GLP-1 deficiency leads to the absence of oocytes at birth. However, the timing and nature of this germ cell loss is not well understood. In this study, we characterize the embryonic germ cell loss in GLP-1 null mice. Quantitative PCR demonstrates that ovarian Glp-1 mRNA is expressed in a bimodal pattern during embryogenesis, peaking at E13.5-14.5 and again at birth. In contrast, adult ovaries express low but detectable levels of Glp-1 mRNA. Analysis of developing GLP-1 null mouse ovaries shows that germ cells are appropriately specified and migrate normally to nascent gonads. Upon arrival at the gonad, precocious loss of germ cells begins at around E13.5. This loss is completed by birth and is accompanied by defects in the expression of genes associated with meiotic entry. Interestingly, somatic pregranulosa cells still form basement membranes surrounding germ line cysts and express mRNA encoding paracrine signaling molecules that communicate with oocytes, albeit at lower levels than normal. Together, these data imply that the somatic cell protein GLP-1 is not necessary for many pregranulosa cell functions but is required for germ cell survival.