Temporal and spatial expression of tissue inhibitors of metalloproteinases during the natural ovulatory cycle of the mouse
Temporal and spatial expression of tissue inhibitors of metalloproteinases during the natural ovulatory cycle of the mouse
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DOI：
10.1095/biolreprod55.3.498
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发表时间：
1996-09-01
影响因子：
3.6
通讯作者：
Khokha, R
中科院分区：
文献类型：
--
作者：
Inderdeo, DS;Edwards, DR;Khokha, R
金属蛋白酶组织抑制因子(TIMPs)在卵巢功能中的作用主要是通过利用激素启动的动物进行的研究来证明的。在这项研究中，我们的目标是阐明单个TIMP基因在自然排卵周期中的时空表达，并将其与特定的生物学事件相关联。两种自然排卵模型分别是小鼠发情周期和产后第一次排卵。分别于动情间期、动情前期、动情后期、动情前期、动情后期、妊娠第17、18天(D17、D18)及产后24、48小时(PP1、PP2)采集小鼠卵巢。我们观察到TIMP-1mRNA在发情前期和日龄18天时升高，在发情后期和产后1天达到最大。TIMP-3的表达模式不同于TIMP-1，表达高峰出现在动情前期、D17和D18。在这两个模型中，TIMP-2mRNA在整个排卵过程中保持不变并处于非常低的水平。原位杂交显示TIMP-1mRNA定位于D18和PP1的黄体，定位于卵泡发育特定阶段的卵母细胞。TIMP-1在颗粒细胞和膜细胞中均未见表达。TIMP-3mRNA仅在第17天定位于卵母细胞、卵泡膜细胞、卵泡膜细胞、卵泡颗粒细胞和黄体细胞。这些数据表明，卵巢中个体时间基因表达的特定激素调节与不同的生理功能有关。我们认为，在自然排卵过程中，TIMP-1可能是调节黄体退化的一个因素，而TIMP-3在维持黄体结构完整性方面起着重要作用。
The role of tissue inhibitors of metalloproteinases (TIMPs) in ovarian function has primarily been documented by studies that utilize hormone-primed animals. In this study, our objectives were to elucidate the spatiotemporal expression of individual TIMP genes during the natural ovulatory cycle, and to correlate these with specific biological events. Two models of spontaneous ovulation used were the murine estrous cycle and the first ovulation postpartum. Ovaries were collected from mice at diestrus, estrus, and metestrus, or at early and late proestrus, and from pregnant females on Days 17 and 18 of gestation (D17, D18) and within 24 or 48 h postpartum (PP1, PP2). We observed that TIMP-1 mRNA was elevated at early proestrus and D18 and was maximal at late proestrus and PP1. The TIMP-3 pattern was distinct from that of TIMP-1, maximal expression occurring at early proestrus and D17 and D18. In both models, TIMP-2 mRNA remained constant and at very low levels throughout ovulation. In situ hybridization localized TIMP-1 mRNA to the corpus luteum at D18 and PP1, and to oocytes at specific stages of follicular development. Expression of TIMP-1 in granulosa and thecal cells was not observed at any stage. Demonstrating a distinct distribution, TIMP-3 mRNA was localized to oocytes, thecal and granulosa cells of small and large follicles, and corpora lutea only at D17. These data suggest specific hormonal regulation of individual TIME gene expression in the ovary associated with distinct physiological functions. We propose that in the natural ovulatory process, TIMP-1 is probably a factor that regulates corpus luteum regression while TIMP-3 is important in maintaining the structural integrity of the corpus luteum.