Oncotarget

Research Papers:

Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway

Lingli Long, Han Qiu, Bing Cai, Ningning Chen, Xiaofang Lu, Shuhui Zheng, Xiaoxin Ye and Yubin Li _

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Oncotarget. 2018; 9:5321-5336. https://doi.org/10.18632/oncotarget.23915

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Abstract

Lingli Long1,*, Han Qiu2,*, Bing Cai6, Ningning Chen3, Xiaofang Lu4, Shuhui Zheng1, Xiaoxin Ye5 and Yubin Li6

1Translation Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

2Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

3Department of Orthopedics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China

4Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

5University of New South Wales, Sydney, Australia

6The Reproductive Center of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Yubin Li, email: liyubin97200@163.com

Keywords: vascular endothelial growth factor; diabetes mellitus; testis; PI3K/Akt pathway; rats sertoli cells

Received: August 24, 2017    Accepted: December 01, 2017    Published: January 04, 2018

ABSTRACT

As an endocrine disease, type 2 diabetes mellitus (T2DM) can cause testicular damage which induces male infertility. However, the underlying mechanism is still not clear. We prove that T2DM induced testicular microcirculation impairment involves the decrease of VEGF and these actions are regulated by PI3K/Akt pathway. In our study, rats were divided into three groups (n=8): control group, diabetes group and diabetes + VEGF group. Intraperitoneal injection of streptozotocin (STZ, 65mg/Kg, at 9th week) and daily high-fat diet were used to establish T2DM rat model. Serum glucose in diabetes group and diabetes + VEGF group obviously exceeded 13mmol/L after STZ injection. Immunohistochemical studies indicated that VEGF level in diabetes group significantly decreased. In diabetes group, testicular blood velocity and vascular area reduced evaluated by Doppler and FITC. Furthermore, atrophic testicular morphology and increasing apoptosis cells were evaluated by haematoxylin and eosin staining and TUNEL assay. In diabetes + VEGF group, the administration of VEGF (intraperitoneally, 10mg/kg) can significantly alleviated hyperglycemia-induced impairment of testes in above aspects. Finally, we used Western blot to analyze the mechanism of hyperglycemia-induced testicular VEGF decrease. The results indicated that hyperglycemia-induced VEGF decreased is regulated by PI3K/Akt pathway in Rats testicular sertoli cells (RTSCs). Together, we demonstrate that T2DM can reduce testicular VEGF expression, which results in testicular microcirculation impairment, and then induces testicular morphological disarrangement and functional disorder. These actions are triggered by PI3K/Akt pathway. Our findings provide solid evidence for VEGF becoming a therapeutic target in T2DM related male infertility.


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