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Epac activation induces an extracellular Ca 2+ ‐independent Ca 2+ wave that triggers acrosome reaction in human spermatozoa
Author(s) -
MataMartínez Esperanza,
SánchezTusie Ana Alicia,
Darszon Alberto,
Mayorga Luis S.,
Treviño Claudia L.,
De Blas Gerardo A.
Publication year - 2021
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12989
Subject(s) - intracellular , extracellular , second messenger system , acrosome reaction , microbiology and biotechnology , thapsigargin , biology , zona pellucida , biophysics , sperm , chemistry , oocyte , embryo , botany
Background The signaling pathways of the intracellular second messengers cAMP and Ca 2+ play a crucial role in numerous physiological processes in human spermatozoa. One such process is the acrosome reaction (AR), which is necessary for spermatozoa to traverse the egg envelope and to expose a fusogenic membrane allowing the egg–sperm fusion. Progesterone and zona pellucida elicit an intracellular Ca 2+ increase that is needed for the AR in the mammalian spermatozoa. This increase is mediated by an initial Ca 2+ influx but also by a release from intracellular Ca 2+ stores. It is known that intracellular Ca 2+ stores play a central role in the regulation of [Ca 2+ ] i and in the generation of complex Ca 2+ signals such as oscillations and waves. In the human spermatozoa, it has been proposed that the cAMP analog and specific agonist of Epac 8‐( p ‐chlorophenylthio)‐2'‐O‐methyladenosine‐3’,5'‐cyclic monophosphate (2'‐O‐Me‐cAMP) elicits an intracellular Ca 2+ release involved in the AR. Objective To identify the molecular entities involved in the Ca 2+ mobilization triggered by 2'‐O‐Me‐cAMP in human spermatozoa. Materials and Methods In capacitated human spermatozoa, we monitored Ca 2+ dynamics and the occurrence of the AR in real time using Fluo 3‐AM and FM4‐64 in a Ca 2+ ‐free medium. Results Epac activation by 2'‐O‐Me‐cAMP induced a Ca 2+ wave that started in the midpiece and propagated to the acrosome region. This Ca 2+ response was sensitive to rotenone, CGP, xestospongin, NED‐19, and thapsigargin, suggesting the participation of different ion transporters (mitochondrial complex I and Na + /Ca 2+ exchanger, inositol 3‐phosphate receptors, two‐pore channels and internal store Ca 2+ ‐ATPases). Discussion Our results suggest that Epac activation promotes a dynamic crosstalk between three different intracellular Ca 2+ stores: the mitochondria, the redundant nuclear envelope, and the acrosome. Conclusion The Ca 2+ wave triggered by Epac activation is necessary to induce the AR and to enhance the flagellar beat.