2. Academic Validation
  3. Ferritinophagy-mediated ferroptosis of spermatogonia is involved in busulfan-induced oligospermia in the mice

Ferritinophagy-mediated ferroptosis of spermatogonia is involved in busulfan-induced oligospermia in the mice

  • Chem Biol Interact. 2024 Jan 12:110870. doi: 10.1016/j.cbi.2024.110870.
Jinyu Xu 1,  Lianshuang Zhang 1,  Yaru Si 2,  Wanyue Huang 3,  Ranran Liu 4,  Zhiyuan Liu 5,  Zhonglin Jiang 1,  Feibo Xu 6
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, College of Basic Medicine, Binzhou Medical University, Yantai, 246003, China; Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, 264003, China.
  • 2 Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, 264003, China; Department of Pharmacology, College of Pharmacy, Binzhou Medical University, Yantai, 264003, China.
  • 3 College of Animal Science and Technology, Anhui Agricultural University, 130 West Changjiang Road, Hefei 230036, China.
  • 4 Clinical Laboratory, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264199, China.
  • 5 College of Clinical Medicine, Bin Zhou Medical University, Yan Tai, 264003, China.
  • 6 Department of Histology and Embryology, College of Basic Medicine, Binzhou Medical University, Yantai, 246003, China; Xu Rongxiang Regenerative Medicine Research Center, Binzhou Medical University, Yantai, 264003, China. Electronic address: xu120190290711@bzmc.edu.cn.
PMID: 38220133 DOI: 10.1016/j.cbi.2024.110870
Abstract

Busulfan, a bifunctional alkylated chemotherapeutic agent, has male reproductive toxicity and induce oligospermia, which is associated with Ferroptosis. However, the specific target cells of busulfan-induced oligospermia triggered by Ferroptosis are largely elusive, and the detailed mechanisms also require further exploration. In the present study, busulfan (0.6, and 1.2 mM, 48 h) causes Ferroptosis in GC-1 spg cells through inducing Fe2+, ROS and MDA accumulation and functional inhibition of Xc-GSH-GPX4 antioxidant system. After inhibition of Ferroptosis by Fer-1 (1 μM, pretreatment for 2 h) or DFO (10 μM, pretreatment for 2 h) reverses busulfan-induced destructive effects in GC-1 spg cells. Furthermore, using RNA-seq and Western blotting, we found that busulfan promotes autophagy-dependent ferritin degradation, as reflected by enriching in Autophagy, increased LC3 II, Beclin1 and NCOA4, as well as decreased P62 and ferritin heavy chain 1 (FTH1). Ultimately, GC-1 spg cells and Balb/c mice were treated with busulfan and/or 3-MA, the inhibitor of Autophagy. The results displayed that inhibition of Autophagy relieves busulfan-induced FTH1 degradation and then blocks the occurrence of Ferroptosis in GC-1 spg cells and testicular spermatogonia, which subsequently alleviates busulfan-caused testicular damage and spermatogenesis disorders. In summary, these data collectively indicated that Ferroptosis of spermatogonia is involved in busulfan-induced oligospermia and mediated by autophagy-dependent FTH1 degradation, identifying a new target for the therapy of busulfan-induced male infertility.

Keywords

Busulfan; Ferritinophagy; Ferroptosis; Oligospermia; Spermatogonia.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z