Mitochondrial Calcium Disorder Affects Early Embryonic Development in Mice through Regulating the ERK/MAPK Pathway

Abstract

The homeostasis of mitochondrial calcium ([Ca2+]mt) in oocytes plays a critical role in maintaining normal reproductive cellular progress such as meiosis. However, little is known about the association between [Ca2+]mt homeostasis and early embryonic development. Two in vitro mouse MII oocyte models were established by using a specific agonist or inhibitor targeting mitochondrial calcium uniporters (MCU) to upregulate or downregulate [Ca2+]mt concentrations. The imbalance of [Ca2+]mt in MII oocytes causes mitochondrial dysfunction and morphological abnormity, leading to an abnormal spindle/chromosome structure. Oocytes in drug-treated groups are less likely to develop into blastocyst during in vitro culture. Abnormal [Ca2+]mt concentrations in oocytes hindered epigenetic modification and regulated mitogen-activated protein kinase (MAPK) signaling that is associated with gene expression. We also found that MAPK/ERK signaling is regulating DNA methylation in MII oocytes to modulate epigenetic modification. These data provide a new insight into the protective role of [Ca2+]mt homeostasis in early embryonic development and also demonstrate a new mechanism of MAPK signaling regulated by [Ca2+]mt that influences epigenetic modification.

Lipid‐lowering activity and underlying mechanism of glycosylated peptide–calcium chelate prepared by transglutaminase pathway

“…Beneficial bacteria help the human body digest and build the balance of the immune system, whereas the increase of harmful bacteria will lead to the disorder of gut microbiota, which easily causes health problems (Zhang et al., 2021). Prebiotics can selectively promote the metabolism and proliferation of beneficial bacteria without stimulating harmful bacteria with potential pathogenic or putrefactive activities, thus improving the health of the host (Zhang, Ansari, et al., 2022). Previously, Chaplin et al.…”

“…The resistin in adipocytes was also decreased significantly ( p < .05) after differentiation with CSPHs‐Ca and XOS‐CSPHs‐Ca‐TG for 8 days, and 100 μg/mL XOS‐CSPHs‐Ca‐TG had a more significant effect ( p < .05) (Figure 4d). Visfatin could act on adipose tissue through the autocrine or paracrine pathway to promote the synthesis, differentiation, and accumulation of adipose tissue (Zhang, Ansari, et al., 2022). After differentiation with CSPHs‐Ca and XOS‐CSPHs‐Ca‐TG, the visfatin in adipocytes significantly decreased ( p < .05) (Figure 4e).…”

“…To further elucidate the signaling pathway that inhibits PPARγ expression and adipogenesis, we next examined whether the MAPK/ERK signaling pathway is activated. The Ca 2+ signal can regulate MAPK/ERK signal pathway through the central RAS protein (Zhang, Liu, et al., 2022). After the extracellular calcium influx, the RAS‐related signal pathway could be activated.…”

HTR1B regulates mitochondrial homeostasis and mitophagy by activating the ERK/ MAPK signalling pathway during human embryonic arrest

“…The MAPK signalling pathway plays a critical role in regulating cell proliferation and differentiation. Moreover, the MAPK/ERK signalling pathway is closely linked to mitochondrial calcium imbalance and its impact on the potential of embryonic development [ 19 ]. In this study, we examined the expression of HTR1B in the chorionic tissue of patients with EA for the first time, and conducted a comprehensive analysis to elucidate the role of HTR1B in post-implantation embryonic development.…”