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ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 3  |  Page : 146-155

Supplementation with L-carnitine rescues sperm epigenetic changes in asthenospermic male semen with altered acetyl-L-carnitine levels


1 Human Sperm Bank, West China Second University Hospital of Sichuan University; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
2 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University; Reproductive Endocrinology and Regulation Laboratory, West China Second University Hospital, Sichuan University, Chengdu 610041, China
3 Human Sperm Bank, West China Second University Hospital of Sichuan University, Chengdu 610041, China
4 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
5 Reproductive Endocrinology and Regulation Laboratory; Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
6 Northeast Pharmaceutical Group, Shenyang 110023; Department of Sports Medicine, Shenyang Sports University, Shenyang 110101, China
7 Human Sperm Bank, West China Second University Hospital of Sichuan University; Reproductive Endocrinology and Regulation Laboratory, West China Second University Hospital, Sichuan University, Chengdu 610041, China

Correspondence Address:
Fu-Ping Li
Human Sperm Bank, West China Second University Hospital of Sichuan University, 1416th Chenglong Road Avenue, Chengdu 610011
China
Wen-Ming Xu
Reproductive Endocrinology and Regulation Laboratory, West China Second University Hospital, Sichuan University, 20th 3 Section of South Renmin Road, Chengdu 610041
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2096-2924.294314

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Objective: To investigate the relationship between the concentration of L-carnitine in semen and sperm parameters and investigate the epigenetic profile in sperm cell after L-carnitine usage. Methods: From February 2017 to February 2018, 46 semen samples from asthenospermic males and 41 semen samples from healthy donors were acquired. Motility parameters were assessed using computer-assisted sperm analysis (CASA, n = 78) and the DNA fragmentation index (DFI) was evaluated through flow cytometry (n = 86), %DFI = % cells outside main population. Other oxidative stress markers, such as reactive oxygen species (ROS) levels (n = 86) and the mitochondria DNA copy numbers, were detected (n = 78). The concentration of L-carnitine and acetyl-L-carnitine was detected (n = 82), and methylation was analyzed (n = 30). After that, we collected 13 fresh semen samples from asthenospermic males and 23 fresh semen samples from healthy donors. These samples were used in a freeze-thaw model that was used to determine whether adding L-carnitine could change sperm progressive motility (n = 23), apoptosis index (n = 9), and methylation analysis (n = 7). In total, we have done 13 asthenospermia samples for Western blot, and except for the poor Western result, we analyzed 6 samples for H3K9ac detection, 7 samples for H3K9m3 and H3K27m3 detection, and immunofluorescence (n = 3). Finally, we had recruited 30 volunteers, and they were given oral administration of L-carnitine for 3 months and then collected semen samples at different time points for methylation analysis. Results: The concentration of acetyl-L-carnitine is negatively correlated with the %DFI value (r2 = 0.1090; P = 0.0026), and the concentration of acetyl-L-carnitine is positively correlated with sperm forward motility (r2 = 0.0543; P = 0.0458) and ROS (r2 = 0.1854;P < 0.0001), and the acetyl-L-carnitine level is negatively correlated with %DFI in asthenospermia (r2 = 0.1701; P = 0.0066), and the level of acetyl-L-carnitine in asthenospermic semen is significantly lower than the normal group (P = 0.0419). In addition, this study indicates that adding L-carnitine significantly improved sperm motility (P = 0.0325) and reduced sperm apoptosis (P = 0.0032). Importantly, Western blotting (P = 0.0429) and immunofluorescence staining results showed that the addition of L-carnitine reduced H3K9Me3 methylation level in sperm, respectively. Furthermore, semen samples from asthenospermic patients had reduced methylation levels in a specific region (16th P = 0.0003; 17th P = 0.0016) of the brain-derived neurotrophic factor (BDNF) promoter. The 16th methylation decreased with age (r2 = 0.1564; P = 0.0306), and the 17th methylation was decreased after treatment with L-carnitine for 28 days (P = 0.0341). Conclusion: L-carnitine can reduce the %DFI and also affect the methylation of the histone modification marker in sperm as a possible epigenetic regulator.


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