Ca2+ Signaling During Mammalian Fertilization: Requirements, Players, and Adaptations

Abstract

Changes in the intracellular concentration of calcium ([Ca 2þ ] i ) represent a vital signaling mechanism enabling communication among cells and between cells and the environment. The initiation of embryo development depends on a [Ca 2þ ] i increase(s) in the egg, which is generally induced during fertilization. The [Ca 2þ ] i increase signals egg activation, which is the first stage in embryo development, and that consist of biochemical and structural changes that transform eggs into zygotes. The spatiotemporal patterns of [Ca 2þ ] i at fertilization show variability, most likely reflecting adaptations to fertilizing conditions and to the duration of embryonic cell cycles. In mammals, the focus of this review, the fertilization [Ca 2þ ] i signal displays unique properties in that it is initiated after gamete fusion by release of a sperm-derived factor and by periodic and extended [Ca 2þ ] i responses. Here, we will discuss the events of egg activation regulated by increases in [Ca 2þ ] i , the possible downstream targets that effect these egg activation events, and the property and identity of molecules both in sperm and eggs that underpin the initiation and persistence of the [Ca 2þ ] i responses in these species.A n increase in the intracellular concentration of calcium ([Ca 2þ ] i ) underlies the initiation, progression and/or completion of a wide variety of cellular processes, including fertilization, muscle contraction, secretion, cell division, and apoptosis (Berridge et al. 2000). To survive and proliferate, cells and organisms must communicate, and changes in [Ca 2þ ] i allow them to quickly respond to environmental, nutritional, or ligand challenges with responses that regulate cell fate and function. Cells devote significant amounts of their energy reserves to create and maintain ionic gradients between extracellular and intracellular milieus and also within the latter, thereby allowing brief alterations in these gradients to have profound signaling effects. In the case of Ca 2þ , myriad proteins have acquired the ability to bind Ca 2þ , which allows them to interpret and transform these elevations into cellular functions. This review will examine the cellular modifications induced by [Ca 2þ ] i changes during fertilization in mature mammalian oocytes, henceforth referred to as eggs.Oocytes during maturation ready themselves for fertilization and the initiation of embryogenesis. During this transition, oocytes undergo changes that include the resumption and progression of meiosis, the development of polyspermy-preventing mechanisms, the reorganization of the cytoskeleton with spindle formation and displacement to the cortex, and the translation, accumulation, and degradation of specific mRNAs and proteins involved in development (Horner and Wolfner 2008b (Stricker 1999;Miyazaki and Ito 2006). Elucidation of the signaling cascades and identification of the molecules/receptor(s) that initiate the Ca 2þ signal at fertilization has proven elusive, and this review will not dwell on th...

Inhibiting Sperm Pyruvate Dehydrogenase Complex and Its E3 Subunit, Dihydrolipoamide Dehydrogenase Affects Fertilization in Syrian Hamsters

“…Calcium signaling is crucial for fertilization [50] and it has been shown recently that calcium influx across the plasma membrane is mandatory for completion of meiosis; especially the extrusion of polar body in the metaphase II arrested oocytes [51] which are in accordance with our observations. It is evident that the molecular changes occurring during sperm capacitation pertinent for calcium influx and eventual oocyte-activation is compromised in the MT-spermatozoa, which are not capacitated properly.…”

Calcium signals regulated by NAADP and two-pore channels - their role in development, differentiation and cancer

“…Ca 2+ signals play important roles throughout embryogenesis, having been implicated in such key developmental stages as fertilization (Parrington et al, 2007, Wakai et al, 2011, Nomikos et al, 2012, Nader et al, 2013, control of cytokinesis (Webb et al, 1997), coordination of complex cell movements during gastrulation (Wallingford et al, 2001), formation of left-right asymmetry (Yoshiba and Hamada 2014), skeletal muscle formation , and development of the nervous system (Leclerc et al, 2012). To date, most studies of NAADP and TPC function during embryogenesis have focused on their role as mediators of Ca 2+ release during activation of the egg at fertilization.…”

Ca2+ homeostasis and regulation of ER Ca2+ in mammalian oocytes/eggs

“…Although the biological significance of [Ca 2+ ] i oscillations in mammalian eggs seems to be ambiguous in terms of embryo development, it might be that episodic [Ca 2+ ] i responses are important for the stepwise completion of the events of egg activation [10, 48]. Generally, different events of egg activation show differential susceptibility to [Ca 2+ ] i increases, and their initiation and completion also have differential Ca 2+ requirements.…”

“…In spite of this knowledge, the mechanisms underlying the enhanced Ca 2+ releasing ability of matured eggs vs. GV oocytes are not well understood, although multiple parameters (e.g. IP 3 R modifications, ER re-organization, increase in [Ca 2+ ] ER ) are thought to be involved in this process [10]. In addition, given that several of the parameters of Ca 2+ homeostasis progressively change during maturation, for instance [Ca 2+ ] ER steadily increases during maturation, the molecules responsible for these adjustments in Ca 2+ homeostasis may experience dynamic modifications during maturation such that some of the mechanisms/channels active at the GV stage may not be so at the MII stage and vice versa.…”