Department of Veterinary Medicine, University of Perugia, 06123 Perugia, Italy.
Department of Veterinary Medicine, University of Milano, 20133 Milano, Italy.
Oxid Med Cell Longev. 2020 Jan 21;2020:4327470. doi: 10.1155/2020/4327470. eCollection 2020.
Infections of the genital tract can perturb the fertility in humans and animals. Pathogen recognition and activation of innate immunity onset through the pattern recognition receptor activation, such as Toll-like receptor 4 (TLR4), leading to the production of proinflammatory cytokines and mediators. TLR4 is expressed both on leukocytes and nonimmune cells. Rabbit TLR4 shows great similarity to its human counterpart. Moreover, the TLR4 signalling pathway could be modulated by long-chain polyunsaturated fatty acids (LC-PUFA). The objectives of this study were (i) to determine the expression levels of TLR4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit and (ii) to evaluate if the n-3 PUFA-enriched diets can modify their expression levels in the tissues and LC-PUFA profiles in seminal plasma. Fifteen rabbit bucks ( = 5/experimental group) were fed with different diets: commercial standard (group C), rich in extruded linseed (10%, group L), and in fish oil (3%, group FO) for 110 days. TLR4, TNF-, and IL-1 mRNA were ubiquitously expressed throughout the hypothalamic-gonadal axis. However, TLR4 mRNA expression was lower in the hypothalamus than the epididymis ( < 0.01), seminal vesicles ( < 0.01), and pituitary gland ( < 0.05). Dietary enrichment in PUFA did not modify the gene expression profile nor the histological characteristics of the tissues. Conversely in seminal plasma, rabbits fed with L and FO had lower n-6 ( < 0.05), LC-PUFA n-6 ( < 0.05), and n-6/n-3 ratio ( < 0.05) but higher n-3 ( < 0.001) and LC-PUFA n-3 ( < 0.01) compared to the control group. Our study builds a map of the gene expression of TRL4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit, fundamental step for understanding the immune defence mechanisms. Diets enriched in LC-PUFA did not affect basal gene expression but modulated sperm fatty acid composition. Finally, rabbit may be an excellent animal model to study the relationship between inflammation and infertility, and the nutritional modulation of immune functions.
生殖道感染会影响人类和动物的生育能力。病原体识别和固有免疫的激活是通过模式识别受体的激活来实现的，如 Toll 样受体 4（TLR4），导致促炎细胞因子和介质的产生。TLR4 既在白细胞上表达，也在非免疫细胞上表达。兔 TLR4 与其人类对应物非常相似。此外，长链多不饱和脂肪酸（LC-PUFA）可以调节 TLR4 信号通路。本研究的目的是：（i）确定 TLR4 和促炎细胞因子在雄性家兔生殖下丘脑-性腺轴中的表达水平；（ii）评估富含 n-3PUFA 的饮食是否可以改变组织中的表达水平以及精液中 LC-PUFA 的谱。15 只公兔（=5/实验组）分别用不同的饮食喂养：商业标准（C 组）、富含挤压亚麻籽（10%，L 组）和富含鱼油（3%，FO 组）110 天。TLR4、TNF-和 IL-1mRNA 在家兔下丘脑-性腺轴的各个部位广泛表达。然而，TLR4mRNA 的表达在下丘脑中低于附睾（<0.01）、精囊（<0.01）和垂体（<0.05）。PUFA 的膳食富集没有改变基因表达谱或组织的组织学特征。相反，在精液中，喂食 L 和 FO 的兔子的 n-6（<0.05）、LC-PUFA n-6（<0.05）和 n-6/n-3 比值（<0.05）较低，但 n-3（<0.001）和 LC-PUFA n-3（<0.01）较高。与对照组相比。本研究构建了雄性家兔生殖下丘脑-性腺轴中 TLR4 和促炎细胞因子基因表达的图谱，这是理解免疫防御机制的基础步骤。富含 LC-PUFA 的饮食不会影响基础基因表达，但会调节精子脂肪酸组成。最后，兔子可能是研究炎症与不孕之间关系以及免疫功能营养调节的理想动物模型。
