Hess K A, Chen L, Larsen W J
Molecular and Developmental Biology, Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA.
Biol Reprod. 1999 Aug;61(2):436-43. doi: 10.1095/biolreprod61.2.436.
This report characterizes the effects of excess hyaluronan (HA) upon the expansion of the cumulus oocyte complex (COC) within intact follicles and upon ovulation and oocyte viability in mice. Covalent linkage between heavy chains of the inter-alpha-inhibitor (IalphaI) family of serum glycoproteins and HA is necessary for optimal cumulus extracellular matrix (cECM) stabilization and cumulus expansion. Intravenous administration of HA oligosaccharides inhibited the binding of IalphaI to endogenous HA, disrupting the process of expansion and resulting in a reduction in the size of the cumulus mass. Western blot and immunocytochemical analyses of COCs from HA-treated animals demonstrated a reduction of IalphaI heavy chains within the cECM. Additionally, HA-treated immature animals ovulated 56.3% fewer COCs compared to control animals. The developmental potential of COCs in HA-treated animals was also tested. Extended periods of oviductal storage of COCs ovulated by HA-injected adult mice resulted in a reduction of normal embryos and a significant increase in the proportion of fragmented oocytes/embryos. These observations support the view that covalent binding of IalphaI heavy chains to HA is required for optimal cumulus expansion, extrusion of the COCs from the follicle at ovulation, and maintenance of oocyte viability within the oviduct.
本报告描述了过量透明质酸(HA)对完整卵泡内卵丘卵母细胞复合体(COC)扩张、小鼠排卵及卵母细胞活力的影响。血清糖蛋白α-抑制因子(IαI)家族重链与HA之间的共价连接对于最佳卵丘细胞外基质(cECM)稳定及卵丘扩张是必要的。静脉注射HA寡糖可抑制IαI与内源性HA的结合,破坏扩张过程,导致卵丘团块大小减小。对HA处理动物的COC进行蛋白质免疫印迹和免疫细胞化学分析表明,cECM内IαI重链减少。此外,与对照动物相比,HA处理的未成熟动物排卵的COC减少了56.3%。还测试了HA处理动物中COC的发育潜力。对HA注射成年小鼠排出的COC在输卵管中延长储存时间后,正常胚胎数量减少,破碎的卵母细胞/胚胎比例显著增加。这些观察结果支持以下观点:IαI重链与HA的共价结合对于最佳卵丘扩张、排卵时COC从卵泡中排出以及输卵管内卵母细胞活力的维持是必需的。