| 報告時間：2024-04-12 |
| 報告地點：Room 407 |
| 指導老師：Pin-Chi Tang |
| 學生：Nguyen Thi Ngoc Han |
| 摘要 |
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It is known that the gonadotropin-releasing hormone (GnRH) derived from the hypothalamus, previously recognized as luteinizing hormone-releasing hormone (LHRH), plays a crucial role in controlling the reproductive endocrine system. GnRH immunocontraception vaccines have been reported as an alternative to surgical castration, aiding in fertility management. The aim of this study was to examine the impact of the UBITh® LHRH immunogen on the reproductive function in male mice. Forty-eight prepubertal ICR male mice at the age of 4 weeks were divided into control (intramuscular injection of sterile phosphate-buffered saline, PBS) and vaccinated groups (intramuscular injection with different doses: T1: 10 μg/0.1 mL; T2: 15 μg/0.15 mL; T3: 20 μg/0.2 mL). Animals were given PBS or LHRH immunogen at the age of 4 and 6 weeks, respectively. Samples were collected and analyzed every two weeks after the first shots. Enzyme-linked immunosorbent assay (ELISA) results revealed a significant difference in serum testosterone concentration between the control group (2180.8±727.9 pg/mL) and the T3 treatment group (836.0±142.4 pg/mL) at 6 weeks post the primary injection. In addition to the increased body weight, results indicated that mice in the groups of T2 and T3 exhibited varying degrees of reduced testicular parameters, including testis weight, length, width, volume, and testis volume/body weight ratio, compared with those in control and T1 groups. It was even more pronounced 8 weeks post initial immunization. The expression of genes-related to reproductive function in the pituitary (LHβ, FSHβ, and GnRHR) and testes (LHR, FSHR, and Gfrα1) significantly decreased in all treatment groups 2 weeks after the first dose of the antigen. Also, it was noted that animal body weight increased while the expression of these genes gradually decreased as time elapsed after injection of immunogen. Compared with those in control and T1 groups, testicular histological sections showed significantly more pronounced testicular atrophy in groups of T2 and T3 6 weeks after antigen injection. The structurally damaged seminiferous tubules, and atrophied interstitial cells (Leydig cells) and epididymal ducts were also observed. Immunohistochemical staining results indicated that the expression of PCNA and STRA8 in the testes from T2 and T3 groups obviously decreased 4 weeks after the first dose of antigen injection. Furthermore, the sperm count, viability, and morphology in the three treatment groups decreased compared with those in the control group at different time points after antigen injection, indicating an adverse effect of antigen treatment on spermatogenesis. In summary, the experimental results indicate that LHRH immunogen can impair male reproductive function in mice, providing a reference to pave the way for development of LHRH immunogens across species. |
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