Podophyllotoxin Exposure Affects Organelle Distribution and Functions in Mouse Oocyte Meiosis.

Ping-Shuang Lu,Yi Xu,Xiao-Han Kong,Shao-Chen Sun,Lan-Ping Xie

doi:10.3389/fcell.2021.672590

Ping-Shuang Lu, Yi Xu + Show 3 more

Open Access

https://doi.org/10.3389/fcell.2021.672590

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Abstract

Podophyllotoxin (POD) is one of the most characterized lignans that is commonly found in podophyllum, and its preparations and derivatives are widely used in clinical treatment due to strong antitumor and antivirus activities. POD has been reported for its neurotoxicity, liver toxicity, and potential reproductive toxicity. In the present study, we investigated the effects of POD on the organelles of mouse oocytes during meiosis. Our results showed that exposure to POD significantly reduced the developmental competence of mouse oocytes. Further analysis revealed that the endoplasmic reticulum (ER) failed to accumulate to the spindle periphery, suggesting that POD exposure might affect protein synthesis during oocyte meiotic maturation. Similarly, abnormal Golgi apparatus distribution was found after POD exposure, which could be confirmed by the aberrant localization of Rab11a-related vesicles, indicating that POD induced vesicle-based protein transport disorder. We also found the aberrant accumulation of lysosomes in the cytoplasm of POD-exposed oocytes, which implied that POD might lead to aberrant protein degradation. Moreover, the perinuclear distribution of mitochondria was also significantly disturbed, indicating the mitochondrial dysfunction after POD exposure. In all, our study illustrated that exposure to POD might disrupt protein synthesis, transport, degradation, and ATP production by its effects on the distribution and functions of organelles during mouse oocyte meiotic maturation.

Highlights

Lignans, as one of the secondary metabolites of plants, are a kind of polyphenols that are widely present in plant tissues such as rhizomes, flowers, leaves, fruits, etc. (Cui et al, 2020)
With its antivirus and antitumor activities, POD preparations are wildly used in the treatment of genital warts, and its derivatives have been adopted as a novel natural anticancer agent
We investigated the distribution of the endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and mitochondria in mouse oocytes after POD exposure

Summary

Introduction

As one of the secondary metabolites of plants, are a kind of polyphenols that are widely present in plant tissues such as rhizomes, flowers, leaves, fruits, etc. (Cui et al, 2020). The alcoholic solution of podophyllin was first proven to be an effective treatment for genital warts in 1942 (Giri and Lakshmi Narasu, 2000). It has been mostly replaced by POD preparations, 0.5% solution or 0.15% cream, and other alternative therapies due to its Abbreviations: POD, podophyllotoxin; GVBD, germinal vesicle breakdown; MI, metaphase I; MII, metaphase II; PB1, first polar body. Podophyllotoxin on Oocyte Organelles high recurrence rate, poor stability, and toxicity (von Krogh and Longstaff, 2001; Wiley et al, 2002; Lacey et al, 2003). The toxin effects of POD on the organelle functions of mammalian oocytes have not been studied

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