Evidence for Increased Expression of SIRT3 Associated with Hyperandrogenism in Granulosa Cells of Non-Obese PCOS Patients

¹ Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China

² Reproductive Medicine Center, The First Affiliated Hospital, Wenzhou Medical University, 325000 Wenzhou, Zhejiang, China

³ The Fist Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, 400016 Chongqing, China

⁴ School of Basic Medical Sciences, Zunyi Medical University, 563003 Zunyi, Guizhou, China

⁵ Institute of Biomedical Engineering, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), 518020 Shenzhen, Guangdong, China

^*Correspondence: shenzhang@cqmu.edu.cn (Shen Zhang)
Academic Editor: Miro Šimun Alebić

Clin. Exp. Obstet. Gynecol. 2022, 49(11), 256; https://doi.org/10.31083/j.ceog4911256

Submitted: 7 May 2022 | Revised: 31 July 2022 | Accepted: 8 August 2022 | Published: 16 November 2022

(This article belongs to the Special Issue Polycystic Ovary Syndrome)

This is an open access article under the CC BY 4.0 license.

Abstract

Background: SIRT3 regulates the generation of reactive oxygen species (ROS) in human granulosa cells (GCs). Increased levels of oxidative stress may cause follicular dysplasia in GCs of polycystic ovary syndrome (PCOS) patients. However, expression and regulation of SIRT3 in GCs of PCOS patients have not yet been investigated. The present study is conducted to determine the correlation between SIRT3 and hyperandrogenism in luteinized GCs of PCOS patients. Methods: The mRNA and protein expression of SIRT3 were analysed in the luteinized GCs from the controls and non-obese PCOS patients. Dihydrotestosterone (DHT) was added to the primary cultured GCs to test the effects of androgen excess on intracellular ROS and SIRT3 expression. A DHT-induced PCOS murine model was used to confirm the effects in vivo. Results: In the matched case-control study including 32 pairs of the controls and non-obese PCOS patients, we showed that the expression of SIRT3 was increased in luteinized GCs of non-obese PCOS patients compared with normovulatory controls. Moreover, DHT induced oxidative stress and SIRT3 expression in human GCs, which was further confirmed in a murine PCOS model. Conclusions: These results indicated that the increased expression of SIRT3 was induced by hyperandrogenism in GCs of non-obese PCOS patients.

Keywords

SIRT3

polycystic ovary syndrome

luteinized granulosa cells

hyperandrogenism

oxidative stress

Funding

cstc2021jcyj-msxmX0097/Natural Science Foundation of Chongqing Municipality

LQ19H040003/Natural Science Foundation of Zhejiang Province

F-585/Natural Science Foundation of Zunyi Medical University

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

Expression of SIRT3 in human GCs between normovulatory women and non-obese PCOS patients. (A) Differential expression of SIRT3 mRNA in GCs between the two groups. Data were expressed as fold changes relative to the control. Bars represent means $\pm$ SD, n = 32. *p $<$ 0.05 vs the control. (B) SIRT3 protein in GCs of the two groups determined by Western blot analysis. The $\beta{}$ -Actin was served as the internal control in both groups. (C) The signal intensities of the western blot bands were assessed by the ImageJ software (NIH). The protein expression of SIRT3 was normalized to $\beta{}$ -Actin. Bars represent means $\pm$ SD, n = 3. *p $<$ 0.05 vs the control.

1 of 3

Clin. Exp. Obstet. Gynecol. Print ISSN 0390-6663 Electronic ISSN 2709-0094