Uteroplacental insufficiency reduces rat plasma leptin concentrations and alters placental leptin transporters: ameliorated with enhanced milk intake and nutrition

Abstract

Uteroplacental insufficiency reduces birth weight and adversely affects fetal organ development, increasing adult disease risk. Cross-fostering improves postnatal nutrition and restores these deficits. Mothers with growth-restricted pups have compromised milk production and composition; however, the impact cross-fostering has on milk production and composition is unknown. Plasma leptin concentrations peak during the completion of organogenesis, which occurs postnatally in rats. Leptin is transferred to the fetus via the placenta and to the pup via the lactating mammary gland. This study investigated the effect of uteroplacental insufficiency on pup plasma leptin concentrations and placental leptin transporters. We additionally examined whether cross-fostering improves mammary development, milk composition and pup plasma leptin concentrations. Fetal growth restriction was induced by bilateral uterine vessel ligation surgery on gestation day 18 in Wistar Kyoto rats (termed uteroplacental insufficiency surgery mothers). Growth-restricted (Restricted) fetuses had reduced plasma leptin concentrations, persisting throughout lactation, and sex-specific alterations in placental leptin transporters. Mothers suckled by Restricted pups had impaired mammary development, altered milk fatty acid composition and increased plasma leptin concentrations, despite no changes in milk leptin. Milk intake was reduced in Restricted pups suckling uteroplacental insufficiency surgery mothers compared to Restricted pups suckling sham-operated mothers. Cross-fostering Restricted pups onto a sham-operated mother improved postnatal growth and restored plasma leptin concentrations compared to Restricted pups suckling uteroplacental insufficiency surgery mothers. Uteroplacental insufficiency alters leptin homeostasis. This is ameliorated with cross-fostering and enhanced milk fatty acid composition and consumption, which may protect the pups from developing adverse health conditions in adulthood.

Uteroplacental insufficiency in rats induces renal apoptosis and delays nephrogenesis completion

“…The delta delta cycle of threshold (C t ) methodology was utilized to determine relative gene abundance compared to the male Control group. 23 Statistical analysis identified that Sdha was not different between treatments or sexes.…”

“…Additional studies are also required to quantify protein expression in the kidney, especially considering leptin's clear ability to impair nephrogenesis. 28 23 thus maintaining a normal nephron endowment despite a poor postnatal environment. These data further highlight that nephrogenesis is delayed or extended in Restricted offspring.…”

“…Custom RT 2 Profiler PCR Arrays were designed and manufactured by Qiagen for the following leptin transporters and signalling targets of interest using SYBR green as the fluorescent agent as described previously. 23 Real-time PCR was used to determine relative abundance of leptin transporters (Megalin and ObR) and their downstream signalling targets (Jak2, Stat3, Stat5a, Socs3 and Pi3k, Akt, mTOR, Ampka, Ampkb). To compensate for variations in RNA quantity and reverse transcriptase efficiency, mRNA abundance of the genes of interest was normalized to the housekeeping gene succinate dehydrogenase subunit A (Sdha; NM_130428).…”

“…10,11,[18][19][20][21] These studies suggest that multiple pathways contribute to the reduction in nephron endowment. We have previously demonstrated that improving the postnatal environment, through crossfostering, restores nephron endowment and prevents disease, 14,15,22,23 which may be due to the benefits of accelerated early postnatal growth. 14,15,22,[24][25][26] However, no studies to date have investigated whether these improvements in nephron endowment are due to changes in branching morphogenesis, renal growth, cellular proliferation and/or apoptosis.…”

Role of omega‐6 and omega‐3 fatty acids in fetal programming

“…Leptin and SREBF‐1 are regulated by nutritional condition and play a central role in regulation of lipogenesis in the adipose tissue and the liver . Further, we have proposed that leptin is an important regulator of organogenesis . Although research has predominantly focused on how exposure to n‐6 FA in pregnancy can programme alterations to lipid regulation in offspring, fewer studies have investigated programming of other physiological systems.…”