■众所周知,代谢紊乱,包括1型糖尿病(T1D),通常与男性生育能力下降有关,主要增加氧化应激和损害下丘脑-垂体-睾丸(HPT)轴,因此改变了精子发生和降低了精子参数。在这里,使用通过用链脲佐菌素(STZ)治疗获得的T1D大鼠模型,我们分析了睾丸活动的几个参数。
■将10只成年雄性Wistar大鼠分为两组,每组5只:对照组和T1D,通过单次腹膜内注射STZ获得。三个月后,将大鼠麻醉并处死;将一个睾丸储存在-80°C用于生化分析,另一个固定用于组织学和免疫荧光分析。
■数据证实T1D诱导氧化应激,因此,睾丸体细胞和生殖细胞的改变。细胞凋亡增强突出了这一方面,改变类固醇生成和Leydig细胞成熟度,精子发生受损。此外,血-睾丸屏障完整性受损,如结构蛋白水平降低(N-钙粘蛋白,ZO-1,闭塞蛋白,连接蛋白43和VANGL2)和调节激酶(Src和FAK)的磷酸化状态。机械上,SIRT1/NRF2/MAPKs信号通路的失调被证明,特别是NRF2的核易位减少,影响其诱导编码抗氧化酶的基因转录的能力。最后,睾丸炎症和焦亡的刺激也得到证实,正如一些标记水平的增加所强调的那样,如NF-κB和NLRP3。
■组合数据使我们能够确认T1D对大鼠睾丸活动具有不利影响。此外,更好地理解代谢紊乱与男性生育力相关的分子机制,可能有助于确定预防和治疗与T1D相关的生育力紊乱的新靶点.
UNASSIGNED: It is well known that metabolic disorders, including type 1 diabetes (T1D), are often associated with reduced male fertility, mainly increasing oxidative stress and impairing the hypothalamus-pituitary-testis (HPT) axis, with consequently altered spermatogenesis and reduced sperm parameters. Herein, using a rat model of T1D obtained by treatment with streptozotocin (STZ), we analyzed several parameters of testicular activity.
UNASSIGNED: A total of 10 adult male Wistar rats were divided into two groups of five: control and T1D, obtained with a single intraperitoneal injection of STZ. After 3 months, the rats were anesthetized and sacrificed; one testis was stored at -80°C for biochemical analysis, and the other was fixed for histological and immunofluorescence analysis.
UNASSIGNED: The data confirmed that T1D induced oxidative stress and, consequently, alterations in both testicular somatic and germ cells. This aspect was highlighted by enhanced apoptosis, altered steroidogenesis and Leydig cell maturity, and impaired spermatogenesis. In addition, the blood-testis barrier integrity was compromised, as shown by the reduced levels of structural proteins (N-cadherin, ZO-1, occludin, connexin 43, and VANGL2) and the phosphorylation status of regulative kinases (Src and FAK). Mechanistically, the dysregulation of the SIRT1/NRF2/MAPKs signaling pathways was proven, particularly the reduced nuclear translocation of NRF2, affecting its ability to induce the transcription of genes encoding for antioxidant enzymes. Finally, the stimulation of testicular inflammation and pyroptosis was also confirmed, as highlighted by the increased levels of some markers, such as NF-κB and NLRP3.
UNASSIGNED: The combined data allowed us to confirm that T1D has detrimental effects on rat testicular activity. Moreover, a better comprehension of the molecular mechanisms underlying the association between metabolic disorders and male fertility could help to identify novel targets to prevent and treat fertility disorders related to T1D.