Pyroptosis and inflammasomes in obstetrical and gynecological diseases

Abstract

Pyroptosis, an inflammatory form of programmed cell death, takes an essential part in a wide variety of physiological activities, for instance, implantation, placentation and the body's defense against infection. However, once excessively activated, pyroptosis mediated by the activation of inflammasomes can be highly pathological. It can cause inflammatory and autoimmune diseases including a variety of obstetrical and gynecological diseases, such as endometriosis, gestational diabetes mellitus, insulin resistance in polycystic ovary syndrome, and multiple obstetric complications including preeclampsia. Although the role of pyroptosis in the pathogenesis of the above mentioned diseases has not been fully elucidated, we try to tap its therapeutic potential by targeting pyroptosis signaling and inflammasome formation. Pyroptosis and inflammasomes are confirmed to be involved in endometriosis and gynecological malignant tumors, therefore, medical approachs inducing pyroptosis of the ectopic endometrium and tumor cells can be feasible treatments for endometriosis and gynecological cancers. On the maternal-fetal interface, although a certain level of the innate immune response activation is required for a successful implantation and placentation, maternal and fetal injury may occur once the inflammasomes are over-activated. Besides, since gestational diabetes mellitus and insulin resistance in polycystic ovary syndrome share common pathogenesis with metabolic diseases, this domain research sheds light on future study of some obstetrical and gynecological diseases.

摘要

细胞焦亡是一种细胞程序性死亡的炎症形式, 在多种生理活动中起着重要作用, 例如, 胎盘植入、胎盘形成和身体对感染的防御。然而, 一旦过度激活, 由炎症体激活介导的焦磷酸症可能是高度病理性的。它可导致炎症和自身免疫性疾病, 包括各种产科和妇科疾病, 如子宫内膜异位症、妊娠期糖尿病、多囊卵巢综合征中的胰岛素抵抗以及包括先兆子痫在内的多种产科并发症。尽管在上述疾病的发病机制中, 细胞焦亡的作用尚未完全阐明, 但我们试图通过靶向细胞焦亡信号和炎症小体的形成来挖掘其治疗潜力。细胞焦亡和炎症小体被证实与子宫内膜异位症和妇科恶性肿瘤有关, 因此, 诱导异位子宫内膜和肿瘤细胞焦亡的医学方法可以作为子宫内膜异位症和妇科癌症的可行治疗方法。在母胎界面上, 虽然成功的着床和胎盘植入需要一定水平的先天免疫反应激活, 但一旦炎症小体过度激活, 母胎就会受到损伤。此外, 由于妊娠期糖尿病和多囊卵巢综合征的胰岛素抵抗与代谢性疾病有着共同的发病机制, 该领域的研究为今后一些妇产科疾病的研究提供了帮助。诱导异位子宫内膜和肿瘤细胞坏死的医学方法是治疗子宫内膜异位症和妇科癌症的可行方法。

Keywords:

• Pyroptosis
• inflammasomes
• endometriosis
• gestational diabetes mellitus
• polycystic ovarian syndrome

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by Natural Science Foundation from Science and Technology Commission of Shanghai Municipality [grant No. 17ZR1403100 to Xue-Lian Li].