The Defensive Role of Cumulus Cells Against Reactive Oxygen Species Insult in Metaphase II Mouse Oocytes

Abstract

We investigated the ability of reactive oxygen species (ROS), such as hydrogen peroxide (H(2)O(2)), hydroxyl radical ((·)OH), and hypochlorous acid (HOCl), to overcome the defensive capacity of cumulus cells and elucidate the mechanism through which ROS differentially deteriorate oocyte quality. Metaphase II mouse oocytes with (n = 1634) and without cumulus cells (n = 1633) were treated with increasing concentration of ROS, and the deterioration in oocyte quality was assessed by the changes in the microtubule morphology and chromosomal alignment. Oocyte and cumulus cell viability and cumulus cell number were assessed by indirect immunofluorescence, staining of gap junction protein, and trypan blue staining. The treated oocytes showed decreased quality as a function of increasing concentrations of ROS when compared to controls. Cumulus cells show protection against H(2)O(2) and (·)OH insult at lower concentrations, but this protection was lost at higher concentrations (>50 μmol/L). At higher H(2)O(2) concentrations, treatment dramatically influenced the cumulus cell number and viability with resulting reduction in the antioxidant capacity making the oocyte more susceptible to oxidative damage. However, cumulus cells offered no significant protection against HOCl at any concentration used. In all circumstances in which cumulus cells did not offer protection to the oocyte, both cumulus cell number and viability were decreased. Therefore, the deterioration in oocyte quality may be caused by one or more of the following: a decrease in the antioxidant machinery by the loss of cumulus cells, the lack of scavengers for specific ROS, and/or the ability of the ROS to overcome these defenses.

Sphingosine‐1‐phosphate (S1P) analog phytosphingosine‐1‐phosphate (P1P) improves the in vitro maturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis

“…Together, these combined similar to those of S1P. However, whether the observed antioxidative effects are through direct actions on oocytes by P1P or via cumulus cells that protect oocytes from OS and express S1PRs is unclear (Cetica, Pintos, Dalvit, & Beconi, 2001;Huang & Wells, 2010;Shaeib et al, 2016).…”

“…Together, these combined observations indicate that P1P improves the quality of IVM oocytes by reducing oocyte intracellular ROS levels possibly via mechanisms similar to those of S1P. However, whether the observed antioxidative effects are through direct actions on oocytes by P1P or via cumulus cells that protect oocytes from OS and express S1PRs is unclear (Cetica, Pintos, Dalvit, & Beconi, ; Huang & Wells, ; Shaeib et al, ).…”

Sphingosine-1-Phosphate (S1P) analogue Phyto-sphingosine-1-Phosphate (P1P) improves thein vitromaturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis

“…Together, these combined observations indicate that P1P improves the quality of IVM oocytes by reducing oocyte intracellular ROS levels possibly via similar mechanisms as S1P. However, it is not entirely clear whether the observed anti-oxidative effects are through direct actions on oocyte by P1P or via cumulus cells known to protect oocytes from OS and express S1PRs [62–64].…”

Metabolic Cooperation in the Ovarian Follicle

“…However, cumulus cells have a significant protective role against the oxidative damage caused by ROS. They show an ability to protect the oocyte against lower levels of H 2 O 2 and •OH (Shaeib et al 2016). When the concentration of H 2 O 2 increases, it dramatically affects the cumulus cell number and this reduction in the antioxidant capacity makes the oocyte more susceptible to oxidative damage (Shaeib et al 2016).…”