Dataset Information

Mechanisms of ROS-induced mitochondria-dependent apoptosis underlying liquid storage of goat spermatozoa

ABSTRACT: Liquid storage of spermatozoa is important for artificial insemination and herd genetic breeding. However, the extending time of storage inducing rapid decline of spermatozoa quality limits the development of this technology. The molecular mechanisms underlying liquid storage of spermatozoa remain largely unexplored. In this study, the effects of liquid storage on functional quality of spermatozoa were assessed in goat (Capra hircus). The time-dependent decline of spermatozoa motility showed a strong correlation with the significant increase of apoptosis. Moreover, apoptosis-related ultrastructural changes were observed, especially the defect in mitochondria. Meanwhile, significant decrease of mitochondrial membrane potential and expression changes of mitochondrial apoptosis-related proteins indicated mitochondrial dysfunction and activation of mitochondrial apoptotic pathway. Notably, the abnormal high level of reactive oxygen species (ROS) caused by liquid storage resulted in the oxidative damage to mitochondria and accelerated mitochondria-dependent apoptosis, which was demonstrated by addition of ROS scavenger N-acetylcysteine. Furthermore, critical differentially expressed proteins involved in mitochondria-dependent apoptosis and antioxidant defense were identified and profiled by quantitative proteomic analysis, facilitating the understanding of molecular regulation of ROS-induced mitochondria-dependent apoptosis. These outcomes provide insights into the mechanisms underlying liquid storage of goat spermatozoa and enhance the progress of semen storage technology.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Capra Hircus (goat)

TISSUE(S): Spermatozoon

SUBMITTER: Tengfei Liu

LAB HEAD: Tengfei Liu

PROVIDER: PXD014609 | Pride | 2019-11-12

REPOSITORIES: Pride

ACCESS DATA

Publications

Mechanisms of ROS-induced mitochondria-dependent apoptosis underlying liquid storage of goat spermatozoa.

Liu Tengfei T Han Yawen Y Zhou Ting T Zhang Ruihang R Chen Hong H Chen Shulin S Zhao Huiying H

Aging 20190923 18

Liquid storage of spermatozoa is important for artificial insemination and herd genetic breeding. However, the extended time of storage inducing the rapid decline in spermatozoa quality limits the development of this technology. The molecular mechanisms underlying liquid storage of spermatozoa remain largely unexplored. In this study, the effects of liquid storage on functional quality of spermatozoa were assessed in goat (<i>Capra hircus</i>). The time-dependent decline in spermatozoa motility ...[more]

PMID: 31548434

Similar Datasets

Project description:Introduction: The flavonoid myricetin has been shown to induce cell cycle arrest and mitochondrial-dependent apoptosis in preclinical cancer models. We hypothesised that myricetin-derived flavonoids with redox properties and improved physicochemical attributes that enhance cell uptake and mitochondrial targeting might have increased potential as antitumour agents, since mitochondria are the main site of production of reactive oxygen species (ROS) and redox status is known to regulate the development and advancement of certain cancers. In this study we assessed a small library of novel flavonoids, then focussed on the lead compound, second-generation analogue OncamexTM, its mechanism of action and structure-activity relationships as an anti-proliferative agent. Methods: With this aim, we studied the effect of OncamexTM in a panel of 7 breast cancer cell lines using proliferation, cytotoxicity and apoptosis assays. The redox properties and mitochondrial delivery of the drug were studied using cyclic voltammetry and fluorescence microscopy, respectively. The mechanism of action was further studied using western blotting, gene expression analysis and immunohistochemistry (IHC) of treated xenograft tissue from in vivo mice models. Results: Sulforhodamine B (SRB) proliferation assays demonstrated strong, anti-proliferative properties of OncamexTM, with IC50 values in the low micromolar range. Treatment for 8 h exerted concentration-dependent reduction in cell viability and induction of cytotoxicity and apoptosis, with increased caspase activation. Microarray analysis suggested that OncamexTM regulates changes in cell cycle and apoptosis at gene expression level. Fluorescence microscopy was used to investigate mitochondrial targeting and ROS regulation in treated cells. OncamexTM was found to induce production of superoxide at concentrations which exerted anti-proliferative effects. Initial in vivo studies in mice implanted with a MDA-MB-231 breast cancer xenograft showed that OncamexTM inhibited tumour growth, reducing tissue viability and Ki-67 proliferation, with no overall systemic toxicity. Conclusions: OncamexTM is a novel flavonoid capable of specific delivery to the mitochondria and induction of ROS production. We have shown its antitumor activity in preclinical models of breast cancer, both in vitro and in initial in vivo models, where tumour growth was arrested without inducing toxicity, support the potential of this novel drug for its continued development as an anticancer agent. Total RNA was obtained from 5 breast cancer cell lines subjected to 6 hours of 10µM OncamexTM and matched untreated controls (1% DMSO)

Dataset Information

Mechanisms of ROS-induced mitochondria-dependent apoptosis underlying liquid storage of goat spermatozoa

Publications

Mechanisms of ROS-induced mitochondria-dependent apoptosis underlying liquid storage of goat spermatozoa.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure