Intrauterine growth retardation promotes fetal intestinal autophagy in rats via the mechanistic target of rapamycin pathway

Abstract

Intrauterine growth retardation (IUGR) impairs fetal intestinal development, and is associated with high perinatal morbidity and mortality. However, the mechanism underlying this intestinal injury is largely unknown. We aimed to investigate this mechanism through analysis of intestinal autophagy and related signaling pathways in a rat model of IUGR. Normal weight (NW) and IUGR fetuses were obtained from primiparous rats via ad libitum food intake and 50% food restriction, respectively. Maternal serum parameters, fetal body weight, organ weights, and fetal blood glucose were determined. Intestinal apoptosis, autophagy, and the mechanistic target of rapamycin (mTOR) signaling pathway were analyzed. The results indicated that maternal 50% food restriction reduced maternal serum glucose, bilirubin, and total cholesterol and produced IUGR fetuses, which had decreased body weight; blood glucose; and weights of the small intestine, stomach, spleen, pancreas, and kidney. Decreased Bcl-2 and increased Casp9 mRNA expression was observed in IUGR fetal intestines. Analysis of intestinal autophagy showed that the mRNA expression of WIPI1, MAP1LC3B, Atg5, and Atg14 was also increased, while the protein levels of p62 were decreased in IUGR fetuses. Compared to NW fetuses, IUGR fetuses showed decreased mTOR protein levels and enhanced mRNA expression of ULK1 and Beclin1 in the small intestine. In summary, the results indicated that maternal 50% food restriction on gestational days 10–21 reduced maternal serum glucose, bilirubin, and total cholesterol contents, and produced IUGR fetuses that had low blood glucose and reduced small intestine weight. Intestinal injury of IUGR fetuses caused by maternal food restriction might be due to enhanced apoptosis and autophagy via the mTOR signaling pathway.

Effects of photoperiod on morphology and function in testis and epididymis of Cricetulus barabensis

“…The balance between autophagy and apoptosis is one of the key factors for maintaining tissue morphology and quality (Campbell & Quadrilatero, 2016; C. Wang et al, 2017), and the application of short daylight results in an increase in DNA fragmentation in Syrian hamsters (Morales et al, 2002; Seco‐Rovira et al, 2014). This may involve the mitochondrial–nuclear apoptosis pathway that is initiated by bax and inhibited by bcl2, in which caspase 3 is the main effector (Antonsson et al, 1997; Manickam, Kaushik, Karunakaran, & Bhansali, 2017).…”

“…The balance between autophagy and apoptosis is one of the key factors for maintaining tissue morphology and quality (Campbell & Quadrilatero, 2016;C. Wang et al, 2017), and the application of short daylight results in an increase in DNA fragmentation in Syrian hamsters (Morales et al, 2002;Seco-Rovira et al, 2014).…”

Novel roles of mechanistic target of rapamycin signaling in regulating fetal growth†

“…In contrast, whole-body deptor mutant KO mice are viable, fertile, and normal in size [37]. Moreover, there is a wealth of evidence that mTOR signaling plays an important role in the growth of individual fetal tissues and organs such as the intestine [38,39], beta cell [40,41], and skeletal muscle [42][43][44][45]. Similarly, decreased tissue growth is associated with inhibition of mTOR signaling in the fetal brown adipose [46], brain [47], heart [48], and thymus [49].…”

Prenatal ethanol exposure induces susceptibility to premature ovarian insufficiency

“…The number of pregnant rats was 16 in each group. The IUGR diagnosis was based on two standard deviations of the foetal rat body weight lower than the mean weight of the control group (Wang et al 2017a). The IUGR incidence was calculated based on the number of IUGR foetuses per litter compared with the total number of pups in the litter (Yu et al 2018).…”