Circular RNA profiling in the oocyte and cumulus cells reveals that circARMC4 is essential for porcine oocyte maturation

Abstract

Thousands of circular RNAs (circRNAs) have been recently discovered in cumulus cells and oocytes from several species. However, the expression and function of circRNA during porcine oocyte meiotic maturation have been never examined. Here, we separately identified 7,067 and 637 circRNAs in both cumulus cells and oocytes via deep sequencing and bioinformatic analysis. Further analysis revealed that a faction of circRNAs is differentially expressed (DE) in a developmental stage-specific manner. The host genes of DE circRNAs are markedly enriched to multiple signaling pathways associated with cumulus cell function and oocyte maturation. Additionally, most DE circRNAs harbor several miRNA targets, suggesting that these DE circRNAs potentially act as miRNA sponge. Importantly, we found that maternal circARMC4 knockdown by siRNA microinjection caused a severely impaired chromosome alignment, and significantly inhibited first polar body extrusion and early embryo development. Taken together, these results demonstrate for the first time that circRNAs are abundantly and dynamically expressed in a developmental stage-specific manner in cumulus cells and oocytes, and maternally expressed circARMC4 is essential for porcine oocyte meiotic maturation and early embryo development.

Analyses stratified by maternal age and recombination further characterize genes associated with maternal nondisjunction of chromosome 21

“…Recent work has shown that ARMC4 circular RNAs are crucial to oocyte maturation in pigs. 40 The top MII variant, rs1855111 (in TMEM72-AS1; Figure 4, maternal MII errors locus #1), attained nominal significance in the MI R0, MI younger, and MI older groups, but did not pass the conservative threshold. Although neither TMEM72-AS1 nor the nearby TMEM72 appear to be involved in meiosis, the gene CXCL12 (470 kb downstream) may play a role in ovine oocyte development.…”

Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

“…What emerges from these studies is surely the maternal contribution in circRNA embryonic inheritance and that circRNAs are actively produced in both oocytes and ovary [263,264]. A genome-wide identification of human ovary circRNAs has been carried out showing circRNA dynamical regulation during ovarian aging, as already suggested for brain [90,263].…”

“…In the ovary, circRNAs have been associated with metabolic processes, serine/threonine metabolism and especially steroid hormone biosynthesis, a critical signaling for normal ovarian functionality. Similarly to the ovary, a circRNA profiling has been examined in both porcine oocyte and cumulus cells revealing 637 and 7067 circRNAs, respectively [264], with potential functions mainly in signal transduction and tight junction regulation, key events in the oocyte-cumulus cell crosstalk.…”

“…Recently, a maternally expressed circRNA-circARMC4-has been selected to explore its role in oocyte maturation. Interestingly, circARMC4 knockdown significantly reduces the rate of oocyte maturation through chromosome misalignment and impairs early embryo development [264].…”

Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts

“…Recently, circRNAs have been found to involve in asthma [ 33 , 34 ] and reproductive system tumors [ 35 ], both of which are closely related to the abnormal puberty, and circRNAs are reported to involve in oocyte maturation and hormone synthesis [ 36 ]. For example, Cao et al showed that circRNAs derived from oocytes exhibit with the characteristics of developmental stage-specific expression [ 37 ]. Xin et al revealed that the depletion of circLDLR inhibits the expression of CYP19A1 , thereby reducing the secretion of estrogen in polycystic ovary syndrome [ 38 ].…”