Alternative polarization of resident macrophages improves hyperglycemia-associated male infertility

Xiaobin Zhu; Zhihong Niu; Weimin Fan; Meiyu Cheng; Qian Chen; Aijun Zhang

doi:10.1016/j.isci.2022.104430

Alternative polarization of resident macrophages improves hyperglycemia-associated male infertility

iScience. 2022 May 18;25(6):104430. doi: 10.1016/j.isci.2022.104430. eCollection 2022 Jun 17.

Authors

Xiaobin Zhu¹, Zhihong Niu¹, Weimin Fan¹, Meiyu Cheng¹, Qian Chen¹, Aijun Zhang¹

Affiliation

¹ Department of Gynecology and Obstetrics, Reproductive Medical Center, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.

Abstract

Recent studies have demonstrated that hyperglycemia induces inflammation in male reproductive system to cause sperm damages and infertility, which may be associated with re-polarization of tissue macrophages from an anti-inflammation M2-like subtype to a pro-inflammation M1-like subtype. However, the underlying mechanisms are not fully determined and a practical approach to interfere with the progression of infertility is lacking. Here, we transduced the testicular macrophages back to the M2-like phenotype with adeno-associated viruses carrying an M2-trigger, Jumonji domain-containing protein D3 (JMJD3), under a macrophage-specific CD68 promoter (CD68p-JMJD3), in streptozotocin-induced diabetic mice. We found that JMJD3-induced M2-polarization of testicular macrophages significantly improved the mating capability of diabetic male mice. The diabetes-induced impairment of the motility of spermatozoa and the decreases in the serum and testicular testosterone levels were both significantly alleviated in CD68p-JMJD3-treated diabetic mice. Thus, our study proposes a practical strategy to treat hyperglycemia-associated infertility.

Keywords: Biological sciences; Cell biology; Components of the immune system; Immunology.