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男性肥胖与精子端粒缩短及自噬相关基因的异常mRNA表达有关。

Male obesity is associated with sperm telomere shortening and aberrant mRNA expression of autophagy-related genes.

作者信息

Raee Pourya, Shams Mofarahe Zahra, Nazarian Hamid, Abdollahifar Mohammad-Amin, Ghaffari Novin Mahsa, Aghamiri Shahin, Ghaffari Novin Marefat

机构信息

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Basic Clin Androl. 2023 May 25;33(1):13. doi: 10.1186/s12610-023-00188-w.

Abstract

BACKGROUND

Obesity is regarded a global public health crisis. It has been implicated in a variety of health problems, but when it comes to male fertility, how and to what extent obesity affects it are poorly understood. Accordingly, semen samples from 32 individuals with obesity (body mass index (BMI) ≥ 30 kg/m) and 32 individuals with normal weight (BMI: 18.5-25 kg/m) were obtained. Here, for the first time, we examined the association between obesity, relative sperm telomere length (STL) and autophagy-related mRNA levels such as Beclin1, AMPKa1, ULK1, BAX, and BCL2. Each group was also evaluated for conventional semen parameters, sperm apoptotic changes, DNA fragmentation index (DFI), sperm chromatin maturation, and reactive oxygen species (ROS) levels.

RESULTS

Based on our findings, there was a marked reduction in relative STL in individuals with obesity as compared to the normal-weight group. We also found a significant negative correlation between relative STL and age, BMI, DFI, percentage of sperm with immature chromatin, and intracellular ROS levels in patients with obesity. In the normal-weight group, relative STL was only negatively correlated with DFI and intracellular ROS levels. Regarding mRNA expression, there was considerable upregulation of Beclin1, ULK1, and BCL2 in the group with obesity compared to the normal-weight group. Obesity was also found to be associated with a considerable decline in semen volume, total sperm count, progressive motility, and viability in comparison to normal-weight individuals. Furthermore, obesity was associated with considerably higher percentages of DFI, sperm with immature chromatin, late-stage apoptosis, and elevated ROS levels.

CONCLUSION

According to our findings, obesity is associated with sperm telomere shortening and aberrant autophagy-related mRNA expression. It should be emphasized that telomere shortening in sperm may be an indirect consequence of obesity due to the oxidative stress associated with the condition. Nevertheless, further investigation is required for a more comprehensive understanding.

摘要

背景

肥胖被视为全球公共卫生危机。它与多种健康问题有关,但在男性生育力方面,肥胖如何以及在多大程度上影响生育力却知之甚少。因此,我们获取了32名肥胖个体(体重指数(BMI)≥30kg/m²)和32名体重正常个体(BMI:18.5 - 25kg/m²)的精液样本。在此,我们首次研究了肥胖、相对精子端粒长度(STL)与自噬相关mRNA水平(如Beclin1、AMPKa1、ULK1、BAX和BCL2)之间的关联。对每组还进行了常规精液参数、精子凋亡变化、DNA碎片化指数(DFI)、精子染色质成熟度和活性氧(ROS)水平的评估。

结果

根据我们的研究结果,与体重正常组相比,肥胖个体的相对STL显著降低。我们还发现肥胖患者的相对STL与年龄、BMI、DFI、染色质未成熟精子百分比和细胞内ROS水平之间存在显著负相关。在体重正常组中,相对STL仅与DFI和细胞内ROS水平呈负相关。关于mRNA表达,与体重正常组相比,肥胖组中Beclin1、ULK1和BCL2有相当程度的上调。与体重正常个体相比,肥胖还与精液量、总精子数、前向运动能力和活力的显著下降有关。此外,肥胖与DFI、染色质未成熟精子、晚期凋亡的百分比显著升高以及ROS水平升高有关。

结论

根据我们的研究结果,肥胖与精子端粒缩短和自噬相关mRNA异常表达有关。应该强调的是,精子端粒缩短可能是肥胖的间接后果,这是由于与该病症相关的氧化应激所致。然而,需要进一步研究以获得更全面的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3915/10210264/10f8e32f2e2e/12610_2023_188_Fig1_HTML.jpg

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