Department of Obstetrics and Gynaecology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK, Leiden, The Netherlands.
Sci Rep. 2022 Jan 11;12(1):430. doi: 10.1038/s41598-021-04069-y.
Obesity can disturb spermatogenesis and subsequently affect male fertility and reproduction. In our study, we aim to elucidate at which cellular level of adult spermatogenesis the detrimental effects of obesity manifest. We induced high fat diet (HFD) obesity in low-density lipoprotein receptor knock-out Leiden (Ldlr.Leiden) mice, and studied the morphological structure of the testes and histologically examined the proportion of Sertoli cells, spermatocytes and spermatids in the seminiferous tubules. We examined sperm DNA damage and chromatin condensation and measured plasma levels of leptin, testosterone, cholesterol and triglycerides. HFD-induced obesity caused high plasma leptin and abnormal testosterone levels and induced an aberrant intra-tubular organisation (ITO) which is associated with an altered spermatids/spermatocytes ratio (2:1 instead of 3:1). Mice fed a HFD had a higher level of tubules in stages VII + VIII in the spermatogenic cycle. The stages VII + VII indicate crucial processes in spermatogenic development like initiation of meiosis, initiation of spermatid elongation, and release of fully matured spermatids. In conclusion, HFD-induced obese Ldlr.Leiden mice develop an aberrant ITO and alterations in the spermatogenic cycle in crucial stages (stages VII and VII). Thereby, our findings stress the importance of lifestyle guidelines in infertility treatments.
肥胖会干扰精子发生，进而影响男性的生育和生殖能力。在我们的研究中，我们旨在阐明肥胖对成年精子发生的有害影响发生在细胞的哪个水平。我们诱导低密度脂蛋白受体敲除莱顿（Ldlr.Leiden）小鼠发生高脂肪饮食（HFD）肥胖，并研究了睾丸的形态结构，以及通过组织学检查评估曲细精管中支持细胞、精母细胞和精子细胞的比例。我们还检查了精子 DNA 损伤和染色质凝聚情况，并测量了血浆中瘦素、睾酮、胆固醇和甘油三酯的水平。HFD 诱导的肥胖导致了高血浆瘦素和异常的睾酮水平，并导致了异常的管内组织（ITO），这与精子细胞/精母细胞比例的改变（2:1 而不是 3:1）有关。喂养 HFD 的小鼠在精子发生周期的 VII+VIII 期有更多的小管。VII+VII 期表明了精子发生发育中的关键过程，如减数分裂的开始、精子细胞伸长的开始以及完全成熟的精子细胞的释放。总之，HFD 诱导的肥胖 Ldlr.Leiden 小鼠在关键阶段（VII 期和 VII 期）出现了异常的 ITO 和精子发生周期的改变。因此，我们的研究结果强调了生活方式指导在不孕治疗中的重要性。
