Reactive oxygen and nitrogen species during meiotic resumption from diplotene arrest in mammalian oocytes

Abstract

Mammalian ovary is metabolically active organ and generates by-products such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) on an extraordinary scale. Both follicular somatic cells as well as oocyte generate ROS and RNS synchronously and their effects are neutralized by intricate array of antioxidants. ROS such as hydrogen peroxide (H(2)O(2)) and RNS such as nitric oxide (NO) act as signaling molecules and modulate various aspects of oocyte physiology including meiotic cell cycle arrest and resumption. Generation of intraoocyte H(2)O(2) can induce meiotic resumption from diplotene arrest probably by the activation of adenosine monophosphate (AMP)-activated protein kinase A (PRKA)-or Ca(2+)-mediated pathway. However, reduced intraoocyte NO level may inactivate guanylyl cyclase-mediated pathway that results in the reduced production of cyclic 3',5'-guanosine monophosphate (cGMP). The reduced level of cGMP results in the activation of cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase 3A (PDE3A), which hydrolyses cAMP. The reduced intraoocyte cAMP results in the activation of maturation promoting factor (MPF) that finally induces meiotic resumption. Thus, a transient increase of intraoocyte H(2)O(2) level and decrease of NO level may signal meiotic resumption from diplotene arrest in mammalian oocytes.

Inhibition of germinal vesicle breakdown by antioxidants and the roles of signaling pathways related to nitric oxide and cGMP during meiotic resumption in oocytes of a marine worm

“…Moreover, taking into account the opposite responses to intraoocytic cAMP in nemerteans vs mammals, these results are consistent with previous data showing that, unlike in nemerteans, NO/cGMP signaling blocks GVBD in rats , Sela-Abramovich et al 2008, Tripathi et al 2009, Pandey et al 2010). …”

“…Based on several lines of evidence, signaling pathways involving the reactive nitrogen species (RNS) nitric oxide (NO) can play a key role in regulating oocyte maturation (Zhang et al 2007, Pandey et al 2010, Tsafriri & Dekel 2010. However, analyses of mammalian oocytes have sometimes presented conflicting data regarding the functions of NO and its common downstream mediator, cGMP (LaPolt 2002), particularly during the resumption of meiotic maturation, as the oocyte undergoes nuclear disassembly (germinal vesicle breakdown (GVBD)); Downs 2010. Thus, mammalian GVBD is often stimulated by antioxidants that can counteract the effects of RNS and reactive oxygen species (ROS;Sun et al 2000, Tao et al 2004a, 2010, Nadri et al 2009, and consistent with these findings, GVBD is prevented or delayed by treatments that elevate intraoocytic NO/cGMP levels (Törnell et al 1990, Faerge et al 2001, Tao et al 2005, Zhang et al 2005, Viana et al 2007, Sela-Abramovich et al 2008.…”

Reduction of nitric oxide level leads to spontaneous resumption of meiosis in diplotene-arrested rat oocytes culturedin vitro

“…Further, Cdc25B expression level was significantly reduced in oocytes that underwent spontaneous resumption of meiosis from diplotene arrest. The high level of intraoocyte cGMP maintains meiotic arrest at diplotene stage in mouse oocyte, 20,43 while decrease of intraoocyte cGMP as well as Cdc25B levels triggers meiotic resumption from diplotene arrest. 4,20,23,30,44,45 Taken together, these data suggest that the decrease of both cGMP as well as Cdc25B levels during spontaneous resumption of meiosis from diplotene arrest possibly by modulating MPF activity.…”

“…30 Changes in the levels of signaling molecules regulate MPF activity and thereby meiotic cell cycle progression from diplotene arrest. 6,19,20,[31][32][33] The MPF is a complex of an enzymatic subunit p 34cdc2 also known as cyclin-dependent kinase 1 (CDK1) and regulatory subunit cyclin B1. 31,33,34 Growing body of evidences suggests that MPF inactivation does not solely dependent on cyclin B1 degradation.…”

Hormonal control of mammalian oocyte meiosis at diplotene stage

“…It will be of interest to examine the regulation of NPPC release, and the phosphorylation sate of NPR2 that is critical for its hormone responsiveness [106]. Furthermore, LH might also increase PDE5 activity and decrease nitric oxide (NO) level, and then decrease intraoocyte cGMP levels [107].…”