Travicic Dijana Z, Miljkovic Dejan, Andric Silvana A, Kostic Tatjana S
Faculty of Sciences, Department of Biology and Ecology, Laboratory for Chronobiology and Aging, Laboratory for Reproductive Endocrinology and Signaling, University of Novi Sad, Dositeja Obradovica Sq 2, Novi Sad, 21000, Serbia.
Faculty of Medicine, University of Novi Sad, Novi Sad, 21000, Serbia.
Reprod Biol Endocrinol. 2025 Jul 17;23(1):104. doi: 10.1186/s12958-025-01440-w.
Circadian desynchrony, caused by a misalignment between the internal biological clock and environmental light cues, is increasingly prevalent in adolescents due to irregular light exposure and social pressures. However, its impact on reproductive maturation remains poorly understood. In this study, the effects of chronic circadian disruption, induced by the 223 light regimen (two days of constant light, two days of constant darkness, and three days of a 14:10 h light-dark cycle), were examined in juvenile and peripubertal male rats (postnatal days 21-49). Gene expression profiles associated with Leydig cell maturation, including steroidogenic, mitochondrial, and clock-related genes, as well as markers of germ cell differentiation, were analyzed alongside functional mitochondrial parameters in Leydig cells. Under control conditions, Leydig cell maturation was marked by increased expression of core clock genes, steroidogenic enzymes (Star, Cyp11a1, Hsd3b1/2), and mitochondrial biogenesis and dynamics markers (Tfam, Nrf1, Cytc, Opa1, Mfn2). These transcriptional changes coincided with rising mitochondrial content, membrane potential, ATP levels, serum androgens, and progression of spermatogenesis. Conversely, the 223-regimen disrupted behavioral rhythms, reduced circulating melatonin, blunted expression of maturation-associated genes, and shifted the acrophase of key steroidogenic and circadian transcripts in 49-day-old rats, indicating altered Leydig cell rhythmicity. These molecular disruptions were accompanied by decreased testosterone levels, altered expression of spermatid differentiation genes (Tnp1 and Prm2), and a reduction in the number of elongated spermatids at stage VII of spermatogenesis. In conclusion, circadian misalignment disrupts endocrine and transcriptional coordination during Leydig cell development, underscoring the vulnerability of pubertal reproductive maturation to environmental light disturbances.
昼夜节律失调是由体内生物钟与环境光信号不同步引起的，由于光照不规律和社会压力，这种情况在青少年中越来越普遍。然而，其对生殖成熟的影响仍知之甚少。在本研究中，我们在幼年和青春期雄性大鼠（出生后第21 - 49天）中研究了由223光照方案（两天持续光照、两天持续黑暗和三天14:10小时明暗循环）诱导的慢性昼夜节律紊乱的影响。分析了与睾丸间质细胞成熟相关的基因表达谱，包括类固醇生成、线粒体和时钟相关基因，以及生殖细胞分化标志物，并同时分析了睾丸间质细胞中的线粒体功能参数。在对照条件下，睾丸间质细胞成熟的标志是核心时钟基因、类固醇生成酶（Star、Cyp11a1、Hsd3b1/2）以及线粒体生物发生和动力学标志物（Tfam、Nrf1、Cytc、Opa1、Mfn2）的表达增加。这些转录变化与线粒体含量增加、膜电位、ATP水平、血清雄激素水平升高以及精子发生进程一致。相反，223方案扰乱了行为节律，降低了循环褪黑素水平，使成熟相关基因的表达减弱，并使49日龄大鼠中关键类固醇生成和昼夜节律转录本的峰值相位发生改变，表明睾丸间质细胞节律性改变。这些分子紊乱伴随着睾酮水平降低、精子细胞分化基因（Tnp1和Prm2）表达改变以及精子发生VII期伸长精子细胞数量减少。总之，昼夜节律失调扰乱了睾丸间质细胞发育过程中的内分泌和转录协调，突出了青春期生殖成熟对环境光干扰的脆弱性。
