Maternal Cytokines CXCL12, VEGFA, and WNT5A Promote Porcine Oocyte Maturation via MAPK Activation and Canonical WNT Inhibition

Abstract

Maternal regulatory factors endow the oocyte with developmental competence in vivo , which might be absent in current in vitro maturation (IVM) systems, thereby compromising oocyte quality. In the present study, by employing RNA sequencing data analysis, we expect to identify potential contributing factors to support porcine oocyte maturation through binding to their receptors on the oolemma. Here, C-X-C motif chemokine ligand 12 (CXCL12), vascular endothelial growth factor A (VEGFA), and Wingless-type MMTV integration site family member 5A (WNT5A), termed CVW, are selected and confirmed to be important maternal cytokines for porcine oocyte maturation. Combined supplementation of CVW promotes the nuclear maturation percentage from 57.2% in controls to 75.9%. More importantly, these maternal cytokines improve the developmental potential of matured oocytes by parthenogenesis, fertilization, and cloning, as their blastocyst formation efficiencies and total cell numbers are increased. CVW supplementation also enlarges perivitelline space and promotes cumulus expansion, which results in a more complete transzonal projection retraction on the zona pellucida, and a reduced incidence of polyspermy in fertilized oocytes. Meanwhile, inhibiting the CVW receptor-mediated signaling pathways severely impairs oocyte meiotic resumption and cumulus expansion during IVM. We further determine that maturation improvement by CVW is achieved through activating the MAPK pathway in advance and inhibiting the canonical WNT pathway at the end of the IVM period. These findings provide a new combination of three cytokines to promote the porcine IVM process, which also holds potential to be used in human assisted reproduction technologies as well as in other species.

Pluripotency and Growth Factors in Early Embryonic Development of Mammals: A Comparative Approach

“…Studies in vitro have shown that VEGF supplementation in bovine and pig embryo culture improves cytoplasmatic maturation and blastocyst development rates [ 52 , 53 ]. Recently, Liu et al, (2020) [ 54 ] showed that VEGF improved embryo development rates in vitro, on the one hand, through activation of the MAPK pathway and, on the other hand, via inhibition of the canonical Wnt pathway during the last step of oocyte maturation.…”

Knockin’ on Egg’s Door: Maternal Control of Egg Activation That Influences Cortical Granule Exocytosis in Animal Species

“…TZPs are actin-and microtubule-rich structures contacting the oocyte (Albertini and Rider, 1994) through gap junctions (Anderson and Albertini, 1976), and transport essential molecules participating in oocyte maturation (Eppig, 1979;Norris et al, 2009;Macaulay et al, 2016). Furthermore, the number of these structures diminishes throughout oocyte maturation by TZPs retraction (Liu et al, 2020). It has been shown that there is a relationship between TZP integrity and the perivitelline space size (Yuan et al, 2017).…”

“…It has been shown that TZPs are involved in polyspermy blockade since an abnormal TZP retraction allows polyspermy. Liu et al (2020) proposed that the expantion of the perivitelline space is necessary to sever the TZP, close the pores of ZP and prevent sperm penetration on the ZP. Thus, avoiding polyspermy (Liu et al, 2020).…”

“…Liu et al (2020) proposed that the expantion of the perivitelline space is necessary to sever the TZP, close the pores of ZP and prevent sperm penetration on the ZP. Thus, avoiding polyspermy (Liu et al, 2020).…”

Initiation of oogenesis and meiosis in the fetal ovary depends on Dennd1a-mediated production of Wnt5a and retinoic acid from the somatic niches

“…In specific somatic niches, Wnt5a-Ror2 pathway suppresses canonical Wnt/β-catenin signaling to limit the proliferation of migratory PGCs and promote their movement [17]. Moreover, Wnt5a promotes oocyte maturation and meiotic resumption during postnatal oocyte development [18,19].…”