Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
PLoS One. 2013 Jul 26;8(7):e69682. doi: 10.1371/journal.pone.0069682. Print 2013.
The aim of this work was to investigate the mechanisms by which chronic malnutrition (CM) affects vas deferens function, leading to compromised reproductive capacity. Previous studies have shown that maternal malnutrition affects the reproductive tracts of adult male offspring. However, little is known about the effects of CM, a widespread life-long condition that persists from conception throughout growth to adult life.
METHODOLOGY/PRINCIPAL FINDINGS: Young adult male rats, which were chronically malnourished from weaning, presented decreased total and haploid cells in the vas deferens, hypertrophy of the muscle layer in the epididymal portion of the vas deferens and intense atrophy of the muscular coat in its prostatic portion. At a molecular level, the vas deferens tissue of CM rats exhibited a huge rise in lipid peroxidation and protein carbonylation, evidence of an accentuated increase in local reactive oxygen species levels. The kinetics of plasma membrane Ca(2+)-ATPase activity and its kinase-mediated phosphorylation by PKA and PKC in the vas deferens revealed malnutrition-induced modifications in velocity, Ca(2+) affinity and regulation of Ca(2+) handling proteins. The severely crippled content of the 12-kDa FK506 binding protein, which controls passive Ca(2+) release from the sarco(endo) plasmic reticulum, revealed another target of malnutrition related to intracellular Ca(2+) handling, with a potential effect on forward propulsion of sperm cells. As a possible compensatory response, malnutrition led to enhanced sarco(endo) plasmic reticulum Ca(2+)-ATPase activity, possibly caused by stimulatory PKA-mediated phosphorylation.
CONCLUSIONS/SIGNIFICANCE: The functional correlates of these cellular and molecular hallmarks of chronic malnutrition on the vas deferens were an accentuated reduction in fertility and fecundity.
本研究旨在探讨慢性营养不良（CM）影响输精管功能的机制，从而导致生殖能力受损。先前的研究表明，母体营养不良会影响成年雄性后代的生殖管道。然而，对于 CM （一种广泛存在的终身疾病，从受孕到生长到成年一直存在）的影响，人们知之甚少。
方法/主要发现：从断奶开始就长期营养不良的年轻成年雄性大鼠，输精管中的总细胞和单倍体细胞减少，输精管附睾部分的肌肉层肥大，前列腺部分的肌肉层严重萎缩。在分子水平上，CM 大鼠的输精管组织中脂质过氧化和蛋白质羰基化显著增加，表明局部活性氧水平明显升高。CM 大鼠输精管质膜 Ca2+-ATP 酶活性及其由 PKA 和 PKC 介导的激酶磷酸化动力学显示，其速度、Ca2+亲和力和 Ca2+处理蛋白的调节发生了营养不良诱导的变化。12kDa FK506 结合蛋白（控制肌浆网/内质网内的 Ca2+被动释放）的含量严重受损，这揭示了与细胞内 Ca2+处理相关的另一个营养不良靶点，可能对精子细胞的向前推进产生影响。作为一种可能的代偿反应，营养不良导致肌浆网/内质网 Ca2+-ATP 酶活性增强，可能是 PKA 介导的磷酸化的刺激作用所致。
结论/意义：这些慢性营养不良对输精管的细胞和分子特征的功能相关性是生育力和繁殖力明显降低。
