SIRT6 Maintains Redox Homeostasis to Promote Porcine Oocyte Maturation

Abstract

SIRT6, the sixth member of the sirtuin family proteins, has been characterized as a crucial regulator in multiple molecular pathways related to aging, including genome stability, DNA damage repair, telomere maintenance, and inflammation. However, the exact roles of SIRT6 during female germ cell development have not yet been fully determined. Here, we assessed the acquisition of meiotic competency of porcine oocytes by inhibition of SIRT6 activity. We observed that SIRT6 inhibition led to the oocyte meiotic defects by showing the impairment of polar body extrusion and cumulus cell expansion. Meanwhile, the compromised spindle/chromosome structure and actin dynamics were also present in SIRT6-inhibited oocytes. Moreover, SIRT6 inhibition resulted in the defective cytoplasmic maturation by displaying the disturbed distribution dynamics of cortical granules and their content ovastacin. Notably, we identified that transcript levels of genes related to oocyte meiosis, oxidative phosphorylation, and cellular senescence were remarkably altered in SIRT6-inhibited oocytes by transcriptome analysis and validated that the meiotic defects caused by SIRT6 inhibition might result from the excessive reactive oxygen species (ROS)-induced early apoptosis in oocytes. Taken together, our findings demonstrate that SIRT6 promotes the porcine oocyte meiotic maturation through maintaining the redox homeostasis.

Supplementation of SDF1 during Pig Oocyte In Vitro Maturation Improves Subsequent Embryo Development

“…Consistent with the fact that ROS in pig oocytes are mainly produced in the mitochondria and trigger damage to the latter [ 19 , 36 ], SDF1-mediated reduction in ROS levels of pig oocytes enhanced the mitochondrial activity of oocytes by increasing the mitochondrial membrane potential. High ROS levels also activate the apoptosis pathways in porcine oocytes [ 37 , 38 , 39 ]. In the present study, we found that SDF1 downregulated the mRNA level of the pro-apoptotic gene BAX , and upregulated the mRNA level of the anti-apoptotic genes BCL2 and GPX4 in the treated pig oocytes.…”

Identification of genes related to sexual differentiation and sterility in embryonic gonads of Mule ducks by transcriptome analysis

“…Such difference might be due to the fact that male germ cells did not enter the meiotic process until puberty, but our samples were derived from the 1/2 embryonic stage (before meiosis). Furthermore, the imbalance between OXPHOS and spermatogonia glycolysis could lead to meiosis failure ( Li Y, et al, 2021 ), which suggested that amino acid metabolism disturbance induced by mitochondrial oxidative phosphorylation might be reason for meiosis failure in male Mule ducks, further resulting in male Mule duck sterility ( Figure 7 ). It should be noted that merely a few amino acid metabolism pathways were enriched by DEGs in inter-breed female comparison in this study ( Figure 3 ).…”

Transcriptome and Proteome Analysis Revealed Key Pathways Regulating Final Stage of Oocyte Maturation of the Turkey (Meleagris gallopavo)

“…The role of SIRT2 and SIRT6 related to the protection of oocytes against aging seems to be interesting, from our point of view. Downregulation of SIRT2 and SIRT6 causes cellular fragmentation, spindle defects, elevated reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and the upregulation of autophagy [ 58 , 62 ]. In our study, the increased expression of SIRT2 and SIRT6 in the mature egg coat of oocytes just before ovulation suggests their important function in the quality control of bird oocytes before fertilization.…”