Reproductive Biology Group, Department of Biological Sciences, California State University, Long Beach, Long Beach, CA 90840, USA.
Reprod Biol Endocrinol. 2010 Jun 25;8:79. doi: 10.1186/1477-7827-8-79.
Matrix metalloproteinases (MMPs) are implicated as mediators for ovarian remodeling events, and are involved with ovarian recrudescence during seasonal breeding cycles in Siberian hamsters. However, involvement of these proteases as the photoinhibited ovary undergoes atrophy and regression had not been assessed. We hypothesized that 1) MMPs and their tissue inhibitors, the TIMPs would be present and differentially regulated during the normal estrous cycle in Siberian hamsters, and that 2) MMP/TIMP mRNA and protein levels would increase as inhibitory photoperiod induced ovarian degeneration.
MMP-2, -9, -14 and TIMP-1 and -2 mRNA and protein were examined in the stages of estrous (proestrus [P], estrus [E], diestrus I [DI], and diestrus II [DII]) in Siberian hamsters, as well as after exposure to 3, 6, 9, and 12 weeks of inhibitory short photoperiod (SD).
MMP-9 exhibited a 1.6-1.8 fold decrease in mRNA expression in DII (p<0.05), while all other MMPs and TIMPs tested showed no significant difference in mRNA expression in the estrous cycle. Extent of immunostaining for MMP-2 and -9 peaked in P and E then significantly declined in DI and DII (p<0.05). Extent of immunostaining for MMP-14, TIMP-1, and TIMP-2 was significantly more abundant in P, E, and DI than in DII (p<0.05). Localization of the MMPs and TIMPs had subtle differences, but immunostaining was predominant in granulosa and theca cells, with significant differences noted in staining intensity between preantral follicles, antral follicles, corpora lutea, and stroma classifications. No significant changes were observed in MMP and TIMP mRNA or extent of protein immunostaining with exposure to 3, 6, 9, or 12 weeks of SD, however protein was present and was localized to follicular and luteal steroidogenic cells.
Although MMPs appear to be involved in the normal ovarian estrus cycle at the protein level in hamsters, those examined in the present study are unlikely to be key players in the slow atrophy of tissue as seen in Siberian hamster ovarian regression.
基质金属蛋白酶（MMPs）被认为是卵巢重塑事件的介质，并参与了西伯利亚仓鼠季节性繁殖周期中的卵巢再生长。然而，这些蛋白酶在光抑制的卵巢发生萎缩和退化过程中的作用尚未得到评估。我们假设：1）MMPs 及其组织抑制剂 TIMPs 将在西伯利亚仓鼠正常发情周期中存在并受到差异调控，2）随着抑制性短光照周期诱导卵巢退化，MMP/TIMPmRNA 和蛋白水平将增加。
在西伯利亚仓鼠发情周期的各个阶段（发情前期[P]、发情期[E]、发情间期 I[DI]和发情间期 II[DII]）以及暴露于 3、6、9 和 12 周抑制性短光照周期（SD）后，检测 MMP-2、-9、-14 和 TIMP-1、-2mRNA 和蛋白。
MMP-9 的 mRNA 表达在 DII 时下降了 1.6-1.8 倍（p<0.05），而其他 MMPs 和 TIMPs 在发情周期中的 mRNA 表达没有显著差异。MMP-2 和 -9 的免疫染色强度在 P 和 E 时达到峰值，然后在 DI 和 DII 时显著下降（p<0.05）。MMP-14、TIMP-1 和 TIMP-2 的免疫染色强度在 P、E 和 DI 时明显高于 DII（p<0.05）。MMPs 和 TIMPs 的定位存在细微差异，但免疫染色主要存在于颗粒细胞和膜细胞中，在窦前卵泡、窦卵泡、黄体和基质分类之间观察到染色强度的显著差异。然而，蛋白存在并定位于卵泡和黄体类固醇生成细胞，暴露于 3、6、9 或 12 周 SD 后，MMP 和 TIMP mRNA 或蛋白免疫染色的程度没有明显变化。
尽管 MMPs 似乎在蛋白水平上参与了仓鼠正常卵巢发情周期，但在本研究中检查的那些不太可能是西伯利亚仓鼠卵巢退化过程中组织缓慢萎缩的关键因素。
