Persistent changes within the intrinsic kidney-associated NPY system and tubular function by litter size reduction

Area of Science:

• Nephrology
• Developmental Biology
• Endocrinology

Background:

• Intrauterine growth restriction (IUGR) increases adult renal disease risk.
• Postnatal factors like nutrition and stress impact kidney development, but their effects on Neuropeptide Y (NPY) signaling are unclear.
• NPY regulates blood pressure and tubular function, but its role in the kidney's response to early life events is not well understood.

Purpose of the Study:

• To investigate the impact of early postnatal environmental factors on renal Neuropeptide Y (NPY) expression and function.
• To determine if litter size reduction (LSR) or intrauterine growth restriction (IUGR) alters NPY signaling pathways in the kidney.
• To assess the functional consequences of these alterations on renal function.

Main Methods:

• Induced IUGR in rats via maternal protein restriction.
• Manipulated postnatal environment by reducing litter size (LSR6, LSR10) or using home-cage controls.
• Analyzed NPY, NPY receptors (Y1, Y2), dipeptidylpeptidase IV (DPPIV), and MAPK signaling at Day 70.
• Assessed renal function, including electrolyte excretion (kaliuresis, natriuresis).

Main Results:

• LSR to 6 neonates, but not IUGR, increased NPY mRNA and decreased NPY receptors Y1 and Y2.
• LSR reduced DPPIV expression and altered mitogen-activated protein kinase 42/44 signaling.
• Renal function was impaired in LSR rats, showing increased kaliuresis and natriuresis at Day 70.

Conclusions:

• Early postnatal environmental factors, such as LSR, dysregulate NPY signaling in the kidney.
• These changes in tubular function due to postnatal environment may predispose to kidney pathology.
• NPY signaling is a critical pathway mediating the long-term effects of early life stress on renal health.