Abstract
BackgroundThe 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 FindingsYoung 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 Ca2+-ATPase activity and its kinase-mediated phosphorylation by PKA and PKC in the vas deferens revealed malnutrition-induced modifications in velocity, Ca2+ affinity and regulation of Ca2+ handling proteins. The severely crippled content of the 12-kDa FK506 binding protein, which controls passive Ca2+ release from the sarco(endo) plasmic reticulum, revealed another target of malnutrition related to intracellular Ca2+ handling, with a potential effect on forward propulsion of sperm cells. As a possible compensatory response, malnutrition led to enhanced sarco(endo) plasmic reticulum Ca2+-ATPase activity, possibly caused by stimulatory PKA-mediated phosphorylation.Conclusions/SignificanceThe functional correlates of these cellular and molecular hallmarks of chronic malnutrition on the vas deferens were an accentuated reduction in fertility and fecundity.
Highlights
It is generally accepted that reproductive performance in the adult is determined by a wide variety of influences, including nutritional status
We demonstrated that chronic malnutrition compromises the reproductive profile in association with atrophy of the prostatic portion of the vas deferens, increased local oxidative stress and adaptive changes in intracellular Ca2+ handling, which are linked to protein kinase-mediated phosphorylation
Recombinant 12-kDa FK506 binding protein (FKBP12), anti-sarco-endoplasmic reticulum Ca2+-ATPase type 2 (SERCA2), anti-protein kinase A (PKA) catalytic subunit and anti-protein kinase C (PKC) antibodies were purchased from Sigma-Aldrich
Summary
It is generally accepted that reproductive performance in the adult is determined by a wide variety of influences, including nutritional status. It is clinically known that among the several forms of undernutrition, the life-long condition characterized by mild-to-moderate protein-energy malnutrition is the most common and is referred to as chronic malnutrition. Under conditions in which contraction is impaired – denervated or rapamycin-treated rat vas deferens – the sarco(endo) plasmic reticulum proteins are down-regulated [8,9], an event that could be associated with a decrease in reproductive capacity [6,10]. With respect to redox signaling, it has recently been demonstrated that reactive oxygen species (ROS) are implicated in male infertility [11] For these reasons, vasa deferentia become an interesting model for evaluating oxidative stress, molecular alterations regarding Ca2+ transport and signaling pathways potentially linked to Ca2+ handling [12], and for correlating these to the loss of reproductive capacity. 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
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