DRP1 deficiency induces mitochondrial dysfunction and oxidative stress-mediated apoptosis during porcine oocyte maturation

Haolin Zhang,Mengmeng Shan,Jiaqian Ju,Shaochen Sun,Chunhua Xing,Xiaohan Li,Zhennan Pan

doi:10.1186/s40104-020-00489-4

Haolin Zhang, Mengmeng Shan + Show 5 more

Open Access

https://doi.org/10.1186/s40104-020-00489-4

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Abstract

BackgroundEnvironmental pollution induces oxidative stress and apoptosis in mammalian oocytes, which can cause defects in reproduction; however, the molecular regulation of oxidative stress in oocytes is still largely unknown. In the present study, we identified that dynamin-related protein 1 (DRP1) is an important molecule regulating oocyte mitochondrial function and preventing oxidative stress/apoptosis. DRP1 is a member of the dynamin GTPase superfamily localized at the mitochondrial-endoplasmic reticulum interaction site, where it regulates the fission of mitochondria and other related cellular processes.ResultsOur results show that DRP1 was stably expressed during different stages of porcine oocyte meiosis, and might have a potential relationship with mitochondria as it exhibited similar localization. Loss of DRP1 activity caused failed porcine oocyte maturation and cumulus cell expansion, as well as defects in polar body extrusion. Further analysis indicated that a DRP1 deficiency caused mitochondrial dysfunction and induced oxidative stress, which was confirmed by increased reactive oxygen species levels. Moreover, the incidence of early apoptosis increased as detected by positive Annexin-V signaling.ConclusionsTaken together, our results indicate that DRP1 is essential for porcine oocyte maturation and that a DRP1 deficiency could induce mitochondrial dysfunction, oxidative stress, and apoptosis.

Highlights

Environmental pollution induces oxidative stress and apoptosis in mammalian oocytes, which can cause defects in reproduction; the molecular regulation of oxidative stress in oocytes is still largely unknown
The results showed that dynamin-related protein 1 (DRP1) was localized in the cytoplasm of porcine oocytes at the germinal vesicle breakdown (GVBD), Metaphase I (MI), and metaphase II (MII) stages (Fig. 1b), and that DRP1 distribution was asymmetric in the cytoplasm, with accumulated signals near the chromosomes
The results showed that the DRP1 signals overlapped with mitochondria, indicating that DRP1 colocalizes with mitochondria during porcine oocyte maturation (Fig. 1c)

Summary

Introduction

Environmental pollution induces oxidative stress and apoptosis in mammalian oocytes, which can cause defects in reproduction; the molecular regulation of oxidative stress in oocytes is still largely unknown. We identified that dynamin-related protein 1 (DRP1) is an important molecule regulating oocyte mitochondrial function and preventing oxidative stress/apoptosis. DRP1 is a member of the dynamin GTPase superfamily localized at the mitochondrial-endoplasmic reticulum interaction site, where it regulates the fission of mitochondria and other related cellular processes. The majority of the oocyte cytoplasm is retained during this process, which contains most of the organelles including mitochondria, providing sufficient storage materials and dynamophore (energy carrier) for early embryonic development after fertilization [2]. Dynamins are a large GTPase superfamily that includes classical dynamins, DRP1, OPA1, Mx proteins, mitofusins and guanylate-binding proteins/atlastins in eukaryotic cells, which are involved in the budding of transport vesicles, division of organelles, cytokinesis, and pathogen resistance [7]. Inactive DRP1 is normally found in the cytosol, while activated DRP1 is translocated to the mitochondrial outer membrane (MOM) [10]

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