South Ehime Fisheries Research Center, Ehime University, Ainan, 798-4206, Japan.
National Research Institute of Aquaculture, Oita, 879-2602, Japan.
Sci Rep. 2017 Jun 9;7(1):3183. doi: 10.1038/s41598-017-03314-7.
Environmental stressors, gonadal degenerative diseases and tumour development can significantly alter the oocyte physiology, and species fertility and fitness. To expand the molecular understanding about oocyte degradation, we isolated several spliced variants of Japanese anchovy hatching enzymes (AcHEs; ovastacin homologue) 1 and 2, and analysed their potential in oocyte sustenance. Particularly, AcHE1b, an ovary-specific, steroid-regulated, methylation-dependent, stress-responsive isoform, was neofunctionalized to regulate autophagic oocyte degeneration. AcHE1a and 2 triggered apoptotic degeneration in vitellogenic and mature oocytes, respectively. Progesterone, starvation, and high temperature elevated the total degenerating oocyte population and AcHE1b transcription by hyper-demethylation. Overexpression, knockdown and intracellular zinc ion chelation study confirmed the functional significance of AcHE1b in autophagy induction, possibly to mitigate the stress effects in fish, via ion-homeostasis. Our finding chronicles the importance of AcHEs in stress-influenced apoptosis/autophagy cell fate decision and may prove significant in reproductive failure assessments, gonadal health maintenance and ovarian degenerative disease therapy.
环境胁迫、性腺退行性疾病和肿瘤发展会显著改变卵子的生理学特性，以及物种的生育力和适应性。为了更深入地了解卵子退化的分子机制，我们分离了几种日本沙丁鱼孵化酶（AcHEs；ovastacin 同源物）1 和 2 的剪接变体，并分析了它们在卵子维持中的潜在作用。特别是 AcHE1b，一种卵巢特异性、类固醇调节、甲基化依赖、应激响应的同工型，被新功能化以调节自噬性卵子退化。AcHE1a 和 2 分别触发卵黄发生和成熟卵子的凋亡性退化。孕酮、饥饿和高温通过超去甲基化增加了总退化卵子群体和 AcHE1b 转录。过表达、敲低和细胞内锌离子螯合研究证实了 AcHE1b 在自噬诱导中的功能意义，可能通过离子稳态来减轻鱼类的应激效应。我们的发现记录了 AcHEs 在应激诱导的细胞凋亡/自噬命运决定中的重要性，这可能对生殖失败评估、性腺健康维护和卵巢退行性疾病治疗具有重要意义。
