Rats undernourished in utero have altered Ca2+ signaling and reduced fertility in adulthood.
Epidemiological and animal studies have shown that placental undernutrition impairs reproduction in adult offspring, but the underlying molecular mechanisms within the male genital tract remain unknown. Due to its special physiological characteristics in transport and the modulation of the environment to which its luminal content is exposed, we hypothesized that the vas deferens would be a highly sensitive target. The goals were to investigate whether intrauterine malnutrition affects molecular mechanisms related to Ca(2+)- and oxidative stress-modulated processes and causes structural alterations in the adult rat vas deferens that could attenuate fecundity and fertility. Male adult rats malnourished in utero had increased vas deferens weight associated with thickening of the muscular coat, a decrease in the total and haploid germ cells, a marked increase in the immature cells, and a decline in the numbers of pregnant females and total offspring per male rat. The ex vivo response of vas deferens from malnourished rats demonstrated an accentuated decrease in the contractile response to phenylephrine. The vas deferens had a marked decrease in Ca(2+) transport due to the uncoupling of Ca(2+)-stimulated ATP hydrolysis and ATP-driven Ca(2+) flux, and the downregulation of both sarco-endoplasmic reticulum Ca(2+)-ATPase 2 and the coupling factor 12-kDa FK506-binding protein. An increase in protein carbonylation (a marker of oxidative damage) and an imbalance between protein kinases C and A were observed as a legacy of undernutrition in early life. These results provide the structural and molecular basis to explain at least in part how maternal undernutrition affects fecundity and fertility in adult male rats.
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
Humberto
H
Muzi-Filho
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Alessandro M
AM
Souza
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Camila G P
CG
Bezerra
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Directorate of Metrology Applied Life Sciences, National Institute of Metrology, Quality and Technology, Duque de Caxias, Brazil.
Leonardo C
LC
Boldrini
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Christina M
CM
Takiya
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Felipe L
FL
Oliveira
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Renata T
RT
Nesi
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Samuel S
SS
Valença
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Ananssa M S
AM
Silva
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Gisele
G
Zapata-Sudo
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Roberto T
RT
Sudo
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
Marcelo
M
Einicker-Lamas
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
Adalberto
A
Vieyra
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil lara@icb.ufrj.br.
Lucienne S
LS
Lara
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Valeria M N
VM
Cunha
Intrauterine malnutrition; oxidative damage markers; reproductive performance; vas deferens calcium handling