Abstract
It has been reported that maternal nutrition determines the offspring’s susceptibility to chronic diseases including cancer. Here, we investigated the effects of maternal diets differing in protein source on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in adult rat offspring. Dams were fed a casein (CAS) diet or a low-isoflavone soy protein isolate (SPI) diet for two weeks before mating and throughout pregnancy and lactation. Offspring were weaned to and fed a chow diet throughout the study. From four weeks of age, hepatocellular carcinomas (HCC) were induced by intraperitoneal injection of DEN once a week for 14 weeks. The SPI/DEN group exhibited higher mortality rate, tumor multiplicity, and HCC incidence compared with the CAS/DEN group. Accordingly, altered cholesterol metabolism and increases in liver damage and angiogenesis were observed in the SPI/DEN group. The SPI/DEN group had a significant induction of the nuclear factor-κB-mediated anti-apoptotic pathway, as measured by increased phosphorylation of IκB kinase β, which may lead to the survival of precancerous hepatocytes. In conclusion, maternal consumption of a low-isoflavone soy protein isolate diet accelerated chemically induced hepatocarcinogenesis in male rat offspring in the present study, suggesting that maternal dietary protein source may be involved in DEN-induced hepatocarcinogenesis in adult offspring.
Highlights
The “fetal basis of adult disease” hypothesis purports that chronic disease in adulthood is determined by in utero nutrition and other environmental factors, which may affect growth, development, and lifespan in mammals [1]
The body weight was significantly reduced in both CAS/DEN and soy protein isolate (SPI)/DEN groups compared with the corresponding control groups after the 6th injection
The final body weight in DEN-treated offspring was significantly lower compared with the maternal diet-matched CON group by 26% and 34% in the CAS and SPI groups, respectively (Figure 2b)
Summary
The “fetal basis of adult disease” hypothesis purports that chronic disease in adulthood is determined by in utero nutrition and other environmental factors, which may affect growth, development, and lifespan in mammals [1]. The altered cell proliferation, differentiation and apoptosis during fetal and neonatal life can modify the development of offspring’s organs, leading to long-term changes to the offspring’s physiology and metabolism [2]. Previous studies have mostly investigated the fetal programming mechanisms that link maternal undernutrition with impaired fetal growth and later development of cardiovascular disease and diabetes [3]. Since the liver is one of the major organs involved in coordinating metabolism, changes in liver development may contribute to a progression of liver disease upon a second hit [4]. Previous studies have reported effects of early life genistein or isoflavone exposure on tumorigenesis, especially in mammary
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
