Proton pump inhibitors affect sperm parameters by regulating aquaporins

Fadian Ding; Yuxin Liu; Jintong Chen; Youzhu Li; Xinxin Guo; Jianmin Wu; Qicai Liu

doi:10.1016/j.heliyon.2023.e17911

Proton pump inhibitors affect sperm parameters by regulating aquaporins

Heliyon. 2023 Jul 1;9(7):e17911. doi: 10.1016/j.heliyon.2023.e17911. eCollection 2023 Jul.

Authors

Fadian Ding¹, Yuxin Liu², Jintong Chen³, Youzhu Li⁴, Xinxin Guo², Jianmin Wu⁵, Qicai Liu^{2

6}

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
² Center of Reproductive Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China.
³ Department of Gastroenterology, 1st Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
⁴ Department of Reproductive Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No. 6 Guchengxi Road, Si Ming, Xiamen, 361003, China.
⁵ Department of Geriatric Medicine, The First Affiliated Hospital of, Fujian Medical University, Fuzhou, China.
⁶ Vanke School of Public Health, Tsinghua University, Beijing, 100084, China.

Abstract

Proton pump inhibitors (PPIs) were one of the most commonly used drugs in daily life. The adverse effects of long-term use of PPIs have aroused widespread controversy. It was of great significance to explore the molecular mechanism of sperm abnormality caused by PPIs. The PPI group was given omeprazole by gavage for 28 days. After the omeprazole intervention, the caudal epididymis was dissected to obtain sperms, and the sperm was counted through the microscope, as the acrosomal integrity was observed through PNA-FITC staining. The expression of aquaporins were detected by immunofluorescence and western blot in the testis, epididymis and spermatozoa. The liver cytochrome enzyme was evaluated by immunohistochemistry and western blot. We detected the serum estrogen level by ELISA, and the level of alanine transaminase (ALT) were detected through microplate method. The sperm count in PPI group was less than control group (p < 0.05), and the sperm acrosin integrity in PPI group was lower than control group (p < 0.05). In the testis, the expression of aquaporin 3 and aquaporin 8 in PPI group was higher than control group (p < 0.05), while the expression of aquaporin 7 was lower than control group (p < 0.05). In the epididymal and sperm, the expression of aquaporin 3 and aquaporin 7 in PPI group was higher than control group (p < 0.05), while the expression of aquaporin 8 in PPI group was lower than control group (p < 0.05). Meanwhile, the liver cytochrome enzyme in PPI group were lower than control group (p < 0.05), and estrogen and ALT in PPI group were higher than control group (p < 0.05). PPI may lead to the up-regulation of estrogen by inhibiting the activity of cytochrome enzyme, and then lead to the dysfunction of sperm parameters and acrosin integrity by affecting aquaporins function.

Keywords: Aquaporins; Cytochrome enzyme; Estrogen; Male infertility; Proton pump inhibitors.