Expression and Contribution of NLRP3 Inflammasome During the Follicular Development Induced by PMSG

Abstract

Follicular development and following ovulation induced by luteinizing hormone (LH) surge are critical for ovarian functions, but the molecular mechanism regulating ovarian ovulation attracts more attention and remains mainly unknown. Recent researches on the nucleotide leukin rich polypeptide 3 (NLRP3) inflammasome shred light on it. Given pregnant mare serum gonadotropin (PMSG) can not only trigger the follicular development, but also induce the following ovulation, the present study therefore examined that expression and localization of NLRP3 inflammasome through immunohistochemistry and Western blotting during the follicular development induced by PMSG. The results showed expressions of NLRP3 and the adaptor protein apoptosis-associated speck-like protein (ASC) significantly increased in the outside of intrafollicular fluid, further analysis found that caspase-1 was activated and IL-1β production was also upregulated after 52 h-treatment of PMSG. Furthermore, a significant increase of ovulation-related genes, hypoxia inducible factor (HIF)-1α and endothelin (ET)-1, was found after 52 h-treatment of PMSG. To our knowledge, it is the first time to clearly indicated the activation of NLRP3 inflammasome may contribute to the ovulation of PMSG-treated ovaries, which will help to further clarify the ovulatory mechanism in mammals.

The Inflammasome Contributes to Depletion of the Ovarian Reserve During Aging in Mice

“…However, our superovulation study did not show an improved ovulation rate in inflammasome-deficient mice. Zhang et al ( 2019 ) demonstrated that follicular expression of ASC and NLRP3 is induced by exogenous hormonal stimulation (e.g., PMSG), suggesting a possible role of NLRP3 inflammasome in the regulation of the ovulatory process (Zhang et al, 2019 ). A possible role for the NLRP3 inflammasome in response to hormonal priming during superovulation might explain why we saw no differences in the number of oocytes ovulated between Asc −/− , Nlrp3 −/− mice, and WT mice.…”

“…However, recent studies indicate that epithelial cells of different tissues can express active inflammasome complexes (Santana et al, 2016 ). In addition, the expression of both NLRP3 protein and the adaptor molecule ASC have been previously detected in the C57BL/6 mouse ovary (Zhang et al, 2019 ). ASC was detected in oocytes, theca cells, and stroma, whereas NLRP3 was localized to the oocytes, theca cells, follicular fluid, and stroma (Zhang et al, 2019 ).…”

“…In addition, the expression of both NLRP3 protein and the adaptor molecule ASC have been previously detected in the C57BL/6 mouse ovary (Zhang et al, 2019 ). ASC was detected in oocytes, theca cells, and stroma, whereas NLRP3 was localized to the oocytes, theca cells, follicular fluid, and stroma (Zhang et al, 2019 ). Furthermore, a recent publication has shown an age-associated accumulation of DAMPs (i.e., lipofuscin) in the ovarian tissue (Urzua et al, 2018 ).…”

Expression Regulation and Physiological Role of Transcription Factor FOXO3a During Ovarian Follicular Development

“…Furthermore, once primordial follicles are formed, their total number remains fixed and is no longer increased. Usually, after the formation of primordial follicles, there will be a continuous batch of developing primordial follicles, and then forming follicles at different developmental stages, finally becoming dominant follicles triggering ovulation to commence a new life journey (Zhang Z. et al, 2019). During follicular development, most follicles die a programmed death or degeneration, which is termed follicular apoptosis or atresia (Tang et al, 2017).…”

Korean Red Ginseng Suppresses the Expression of Oxidative Stress Response and NLRP3 Inflammasome Genes in Aged C57BL/6 Mouse Ovaries

“…ROS stimulates the activation of NLRP3 inflammasome [27], which is a protein complex that initiates an inflammatory response [28,29] that damages ovaries when excessive [30]. Therefore, we next determined whether KRGSF affects the expression of genes encoding NLRP3 inflammasome components by quantitative RT-PCR ( Figure 6A).…”