Undernutrition affects cell survival, oxidative stress, Ca2+ handling and signaling pathways in vas deferens, crippling reproductive capacity.
BACKGROUND
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.


RESULTS
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
The functional correlates of these cellular and molecular hallmarks of chronic malnutrition on the vas deferens were an accentuated reduction in fertility and fecundity.
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Humberto
H
Muzi-Filho
Camila G P
CG
Bezerra
Alessandro M
AM
Souza
Leonardo C
LC
Boldrini
Christina M
CM
Takiya
Felipe L
FL
Oliveira
Renata T
RT
Nesi
Samuel S
SS
Valença
Marcelo
M
Einicker-Lamas
Adalberto
A
Vieyra
Lucienne S
LS
Lara
Valeria M N
VM
Cunha
D000375:Aging / Q000473:pathology; D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival; D002908:Chronic Disease; D004822:Epididymis / Q000473:pathology; D006238:Haploidy; D007700:Kinetics; D008297:Male; D044342:Malnutrition / Q000201:enzymology / Q000473:pathology*; D009132:Muscles / Q000473:pathology; D009929:Organ Size; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction; D013094:Spermatozoa / Q000473:pathology; D013737:Testis / Q000473:pathology; D014649:Vas Deferens / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
D000252:Calcium-Transporting ATPases; D002118:Calcium