Transient Scrotal Hyperthermia Induces Lipid Droplet Accumulation and Reveals a Different ADFP Expression Pattern between the Testes and Liver in Mice

Liu, Mingxi; Lin, Qingsong; Zeng, Yan; Yang, Yang; Bi, Ye; Shi, Xiaodan; Zhu, Hui; Zhou, Zuomin; Sha, Jiahao

doi:10.1371/journal.pone.0045694

Cited by 21 publications

(19 citation statements)

References 42 publications

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“…This not only coincided with peak levels of CE and ADG in the rat testis, but concurred with a considerable buildup of lipid droplets in SC, in agreement with the finding that these two neutral lipid classes are mostly SC products [16]. The buildup of lipid droplets consequent to heat exposures was elegantly confirmed shortly afterwards in the mouse testis in vivo , where the expression of two lipid droplet-specific proteins, PLIN2 and PLIN3, was shown to increase after similarly short but daily repeated exposures to moderate hyperthermia [17].…”

Section: Introductionsupporting

confidence: 84%

Altered Lipid Homeostasis in Sertoli Cells Stressed by Mild Hyperthermia

2014

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Spermatogenesis is known to be vulnerable to temperature. Exposures of rat testis to moderate hyperthermia result in loss of germ cells with survival of Sertoli cells (SC). Because SC provide structural and metabolic support to germ cells, our aim was to test the hypothesis that these exposures affect SC functions, thus contributing to germ cell damage. In vivo, regularly repeated exposures (one of 15 min per day, once a day during 5 days) of rat testes to 43°C led to accumulation of neutral lipids. This SC-specific lipid function took 1–2 weeks after the last of these exposures to be maximal. In cultured SC, similar daily exposures for 15 min to 43°C resulted in significant increase in triacylglycerol levels and accumulation of lipid droplets. After incubations with [3H]arachidonate, the labeling of cardiolipin decreased more than that of other lipid classes. Another specifically mitochondrial lipid metabolic function, fatty acid oxidation, also declined. These lipid changes suggested that temperature affects SC mitochondrial physiology, which was confirmed by significantly increased degrees of membrane depolarization and ROS production. This concurred with reduced expression of two SC-specific proteins, transferrin, and Wilms' Tumor 1 protein, markers of SC secretion and differentiation functions, respectively, and with an intense SC cytoskeletal perturbation, evident by loss of microtubule network (α-tubulin) and microfilament (f-actin) organization. Albeit temporary and potentially reversible, hyperthermia-induced SC structural and metabolic alterations may be long-lasting and/or extensive enough to respond for the decreased survival of the germ cells they normally foster.

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Section: Introductionsupporting

confidence: 84%

Altered Lipid Homeostasis in Sertoli Cells Stressed by Mild Hyperthermia

2014

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“…This strategy produced a rapid site-specific MHT treatment attained within 90 sec and sustained for ~ 20 min by pulsed irradiation (Figure 1). MHT treatment was more rapid than water-bath heating which takes more than 2 min to reach desired temperatures [43] . It also allowed a more accurate and deeper actuation of tumor microenvironment properties (Figure 1 A).…”

Section: 0 Discussionmentioning

confidence: 99%

Mild Hyperthermia Enhances Transport of Liposomal Gemcitabine and Improves In Vivo Therapeutic Response

Kirui

Celia

Molinaro

et al. 2015

Adv Healthcare Materials

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Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod-mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery and anti-tumor efficacy in pancreatic cancer CAPAN-1 tumor model. MHT treatment led to a 3-fold increase in accumulation of 80-nm liposomes and enhanced spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment led to a 3-fold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg/kg Gem Lip led to a 2-fold increase in therapeutic efficacy and inhibition of CAPAN-1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect was confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg/kg Gem Lip achieved similar therapeutic efficacy as the use of 60 mg/kg free gemcitabine. In conclusion, we demonstrated improvements in vivo efficacy resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines.

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“…Finally, embryos were mounted on glass slides with 1, 4-diazabicyclo [2.2.2] octane and examined under a ZEISS LSM 710 confocal laser scanning microscope (Carl ZEISS MicroImaging). ZEN (Zeiss Efficient Navigation) 2009 Light Edition software equipped with LSM Systems was used for data analysis as previously described [17,18,19]. The same parameters were used for microscopic analysis of the experimental and control groups.…”

Section: Methodsmentioning

confidence: 99%

Expression and Potential Role of microRNA-29b in Mouse Early Embryo Development

Zhang

Wang²,

Liu³

et al. 2015

Cell Physiol Biochem

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Background/Aims: MicroRNA-29b (miR29b) has been previously identified in early mouse embryos through miRNA microarray analysis. Recent research has indicated that miR29b participates in DNA methylation by regulating DNA methyltransferase 3a/3b (Dnmt3a/3b) expression. However, the expression pattern and biological function of miR29b in mouse preimplantation embryonic development remain unknown. Methods: In this study, we examined the expression patterns of miR29b and Dnmt3a/3b in mouse early embryos at different developmental stages. Subsequently, expression and localization of DNMT3A/3B protein was analyzed in mouse early embryos by immunofluorescence staining. The biological function of miR29b in mouse early embryos was analyzed by microinjection of commercially available miRNA-specific inhibitors and mimics. Results: Our data showed that Dnmt3a/3b mRNA expression is negatively regulated by miR29b in mouse early embryos. Immunofluorescence analysis revealed that DNMT3A/3B protein expression is predominantly localized within the nucleoplasm of embryos. Alterations to the activity of miR29b could change the DNA methylation levels in mouse preimplantation embryos and lead to a developmental blockade, from the morula to the blastocyst stage. Conclusion: These results indicated a role for the miR29b-Dnmt3a/3b-DNA methylation axis in mouse early embryonic development, and we provide evidence that miR29b is indispensable for mouse early embryonic development. This study contributes to a preliminary understanding of the role of miR29b during mouse embryonic development.

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Transient Scrotal Hyperthermia Induces Lipid Droplet Accumulation and Reveals a Different ADFP Expression Pattern between the Testes and Liver in Mice

Cited by 21 publications

References 42 publications

Altered Lipid Homeostasis in Sertoli Cells Stressed by Mild Hyperthermia

Altered Lipid Homeostasis in Sertoli Cells Stressed by Mild Hyperthermia

Mild Hyperthermia Enhances Transport of Liposomal Gemcitabine and Improves In Vivo Therapeutic Response

Expression and Potential Role of microRNA-29b in Mouse Early Embryo Development

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