Lrriq1 是通过抑制细胞凋亡来维持生育能力的必需因素。

Lrriq1 is an essential factor for fertility by suppressing apoptosis.

机构信息

Department of Pharmaceutical Information Science, Tokushima University Graduate School of Biomedical Sciences, 1-78-1 Sho-machi, Tokushima, Tokushima, 770-8505, Japan.

出版信息

J Assist Reprod Genet. 2022 Nov;39(11):2647-2657. doi: 10.1007/s10815-022-02623-9. Epub 2022 Sep 21.

DOI:10.1007/s10815-022-02623-9

PMID:36129630

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9723037/

Abstract

PURPOSE

Leucine-rich repeats and IQ motif containing 1 (LRRIQ1) gene is reportedly associated with plasma inhibin B levels. However, the function of LRRIQ1 remains unknown. In this study, we generated Lrriq1 knockout mice (Lrriq1 mice) and examined the effects of LRRIQ1 on inhibin B and fertility.

METHODS

Lrriq1 mice were generated using CRISPR/Cas9 genome editing technology. The expression of Inhibin B was examined by Western blotting using a protein extracted from the testis of a 3-month-old male mouse. Mating experiments were conducted using 7-week-old Lrriq1 mice and wild-type (WT) mice to examine fertility. Sperm concentration and sperm motility were measured using 3-month-old male mice.

RESULTS

Expression analysis of inhibin B revealed that Lrriq1 mice exhibited reduced mRNA and protein levels of inhibin alpha (Inha), which constitutes the α subunit. In the mating experiment, the litter size of Lrriq1 male mice was 4.3 ± 2.9, which was significantly lower than that of WT male mice (8.3 ± 1.3) (p < 0.001). No difference in sperm count was observed between Lrriq1 and WT male mice; however, sperm motility (%) was significantly reduced in Lrriq1 mice (48.4 ± 4.9) when compared with WT mice (70.2 ± 4.7) (p < 0.001). Based on TUNEL staining, the testes and epididymal sperm of Lrriq1 mice showed high numbers of apoptosis-positive cells.

CONCLUSION

Lrriq1 knockout reduced sperm motility and litter size by inducing apoptosis of testicular germ cells and epididymal sperm.

摘要

目的

富含亮氨酸重复和 IQ 基序的 1 号（LRRIQ1）基因据称与血浆抑制素 B 水平有关。然而，LRRIQ1 的功能仍然未知。在这项研究中，我们生成了 Lrriq1 敲除小鼠（Lrriq1 小鼠），并研究了 LRRIQ1 对抑制素 B 和生育力的影响。

方法

使用 CRISPR/Cas9 基因组编辑技术生成 Lrriq1 小鼠。通过使用从 3 个月大雄性小鼠的睾丸中提取的蛋白质进行 Western blot 分析，检查抑制素 B 的表达。使用 7 周龄的 Lrriq1 小鼠和野生型（WT）小鼠进行交配实验，以检查生育能力。使用 3 个月大的雄性小鼠测量精子浓度和精子活力。

结果

抑制素 B 的表达分析表明，Lrriq1 小鼠表现出抑制素 α（Inha）的 mRNA 和蛋白水平降低，Inha 构成α亚基。在交配实验中，Lrriq1 雄性小鼠的产仔数为 4.3±2.9，明显低于 WT 雄性小鼠（8.3±1.3）（p<0.001）。Lrriq1 和 WT 雄性小鼠的精子计数没有差异；然而，Lrriq1 小鼠的精子活力（%）显著降低（48.4±4.9），而 WT 小鼠的精子活力（70.2±4.7）（p<0.001）。基于 TUNEL 染色，Lrriq1 小鼠的睾丸和附睾精子显示出大量凋亡阳性细胞。