In this study published in the journal Nutrition Research, a team of researchers from the David Geffen School of Medicine at the University of California, Los Angeles investigated the mechanisms underlying intrauterine growth restriction (IUGR) using a mouse model. They evaluated key cytokines like interleukin-10 (IL-10), cellular processes related to immunity, and the resulting IUGR phenotype and placental histopathology to determine the immunologic pathways affected by IUGR.

• IUGR affects up to 10 percent of pregnancies and often has short- and long-term consequences for offspring.
• It is known that a healthy placenta is essential for nutrient provision to fuel fetal growth, and it is regulated by immunologic inputs.
• The researchers hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death.
• To test this hypothesis, they subjected pregnant mice to mild and moderate FR from gestational day 10 to 19, collecting placentas and embryos at gestational day 19.
• They used RNA sequencing to identify immunologic pathways affected in IUGR-associated placentas and validated messenger RNA expression changes of genes important in cellular integrity.
• The researchers also evaluated histopathological changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, endoplasmic reticulum (ER) stress, and apoptosis in the mouse placentas.
• They identified several differentially expressed genes in FR compared with control mice, including a considerable subset that regulates immune tolerance, inflammation, and cellular integrity.
• They found that maternal FR decreases the anti-inflammatory effect of IL-10 and suppresses placental autophagic and ER stress responses, despite the presence of dysregulated vascular and trophoblast structures that lead to IUGR.

The researchers concluded that FR causes IUGR by triggering changes in gene expression in a placental level that involves immunologic pathways and associated cellular maintenance processes.

Journal Reference:

Chu A, Thamotharan S, Ganguly A, Wadehra M, Pellegrini M, Devaskar SU. GESTATIONAL FOOD RESTRICTION DECREASES PLACENTAL INTERLEUKIN-10 EXPRESSION AND MARKERS OF AUTOPHAGY AND ENDOPLASMIC RETICULUM STRESS IN MURINE INTRAUTERINE GROWTH RESTRICTION. Nutrition Research. October 2016;36(10):1055–1067. DOI: 10.1016/j.nutres.2016.08.001