Regulation of [Ca2+]i oscillations and mitochondrial activity by various calcium transporters in mouse oocytes

Feng Wang,Xiang-Hong Ou,Li-Juan Wang,Ang Li,Heide Schatten,Tie-Gang Meng,Le-Yun Wang,Yi Hou,Qing-Yuan Sun

doi:10.1186/s12958-020-00643-7

Abstract

Oocyte activation inefficiency is one of the reasons for female infertility and Ca2+ functions play a critical role in the regulation of oocyte activation. We used various inhibitors of Ca2+ channels located on the membrane, including sarcoplasmic/ endoplasmic reticulum Ca2+ATPases (SERCAs, the main Ca2+ pumps which decrease the intracellular Ca2+ level by refilling Ca2+ into the sarcoplasmic reticulum), transient receptor potential (TRP) ion channel subfamily member 7 (TRPM7, a Ca2+/Mg2+-permeable non-selective cation channel), T-type Ca2+ channels and calcium channel Orai1, to investigate their roles in [Ca2+]i oscillation patterns and mitochondrial membrane potential during oocyte activation by real-time recording. Our results showed that SERCAs, TRPM7 and T-type Ca2+ channels were important for initiation and maintenance of [Ca2+]i oscillations, which was required for mitochondrial membrane potential elevation during oocyte activation, as well as oocyte cytoskeleton stability and subsequent embryo development. Increasing the knowledge of calcium transport may provide a theoretical basis for improving oocyte activation in human assisted reproduction clinics.

Highlights

According to reports by the World Health Organization in 2016, at least one of ten couples in developed countries cannot have children within 5 years of marriage, half of which are due to female infertility [1]
Inhibitors of Ca2+ channels affect the efficiency of oocyte activation We firstly examined the dose-dependent effects of inhibitors of sarcoplasmic reticulum/Endoplasmic reticulum (ER) CaATPase (SERCAs), TRPM7, T-type Ca2+ channels and Orai1 on the efficiency of SrCl2-induced oocyte parthenoactivation and found a suitable concentration
Oocyte activation induces a continuous series of oocyte intracellular Ca2+ concentration ([Intracellular Ca2+ Concentration (Ca2+]i)) increases and decreases known as [Ca2+]i oscillations, which encode oocyte activation events, including release from the Metaphase II (MII) arrest, pronuclear formation and the transition to embryo development [29]

Summary

Introduction

According to reports by the World Health Organization in 2016, at least one of ten couples in developed countries cannot have children within 5 years of marriage, half of which are due to female infertility [1]. Oocyte activation inefficiency is a major problem causing female infertility [2]. Oocyte activation begins with a series of crucial steps triggered by periodical repetitive increases and decreases of intracellular Ca2+ ([Ca2+]i) concentrations known as [Ca2+]i oscillations [3, 4]. The importance of Ca2+ functions in the regulation of oocyte activation is increasingly being recognized [6]. There are many important channel proteins involved in Ca2+ transport in oocytes. Ca2+ influx into the cytoplasm is mediated by a diverse population of Ca2+ transporters exhibiting significant diversities in their gating and activation mechanisms. Once the oocyte is activated, the [Ca2+]i oscillations are produced by simultaneous intracellular Ca2+ storage release and the extracellular Ca2+ influx [8]

Methods

Results

Conclusion