Rats undernourished in utero have altered Ca²⁺signaling and reduced fertility in adulthood

Abstract

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 Ca2+- 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 Ca2+ transport due to the uncoupling of Ca2+-stimulated ATP hydrolysis and ATP-driven Ca2+ flux, and the downregulation of both sarco-endoplasmic reticulum Ca2+-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.

Macrophage and adipocyte interaction as a source of inflammation in kidney disease

“…Kidney sections of control and adenine diet mice were stained with Masson Trichrome in our pathology core. An interstitial fibrosis (IF) score was obtain using previously described criteria 49 – 51 on at least 10 randomly selected areas at 20× magnification in in each mice. Scores were verified by 2 different investigators blinded to the study groups.…”

Cardiac Inflammation after Ischemia-Reperfusion of the Kidney: Role of the Sympathetic Nervous System and the Renin-Angiotensin System

“…The activity of PKA was assessed by quantification of the rate of incorporation of [γ-32 P]ATP γ-phosphoryl group (specific activity of approximately 1.5 × 10 11 Bq/mmol) into histone in the absence or presence of PKAi, the specific inhibitor of PKA (final concentration 10 nM) [39][40][41]. The activity was expressed in pmol P~histone × mg -1 × min -1 ).…”

Different antihypertensive and metabolic responses to rostafuroxin in undernourished and normonourished male rats: Outcomes on bodily Na+ handling

“…Composition according to the Laboratory of Experimental and Analysis of Food (LEEAL), Nutrition Department, Federal University of Pernambuco (Teodósio et al, 1990 ). d Average values reported by the supplier (CTRL diet) and by Muzi‐Filho et al ( 2015 ) (RBD). For the determinations of Na + intake and Na + balance in the present study, the dietary Na + content was measured in each food sample by flame photometry (see Materials and Methods, Section 2.6 ).…”

“… d Average values reported by the supplier (CTRL diet) and by Muzi‐Filho et al ( 2015 ) (RBD). For the determinations of Na + intake and Na + balance in the present study, the dietary Na + content was measured in each food sample by flame photometry (see Materials and Methods, Section 2.6 ).…”