Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring

Abstract

Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P < 0·05). The thymic cortico-medullar ratio was lower in adult offspring exposed to mLPD (P < 0·05). At PND180, the protein expression of the lymphotoxin β receptor (P < 0·05), the autoimmune regulator (P < 0·05) and Forkhead Box P3 (FoxP3; P < 0·05) was all significantly lower in the mLPD group. The CD4+:CD8+ single-positive thymocyte subpopulation ratio and CD4+:CD8+ lymphocyte subpopulation ratio were increased in the mLPD group (P < 0·05). Among CD3+ lymphocytes, the proportions of CD4+CD8+ double-positive lymphocytes, CD31+ recent thymic emigrants and CD4+FoxP3+ lymphocytes were not significantly different between mLPD and control groups. These findings suggest mLPD during gestation induced long-lasting alterations in the development of thymic structure and thymic cell maturation and selection process in adult male rat offspring.

Maternal Protein Restriction Altered Insulin Resistance and Inflammation-Associated Gene Expression in Adipose Tissue of Young Adult Mouse Offspring in Response to a High-Fat Diet

“…Our findings suggest that maternal low-protein consumption followed by postweaning high-fat diet provided a detrimental effect on immune system development. Consistently, previous studies reported that thymus structure and function in adult offspring can be impaired by maternal protein restriction during pregnancy [56], and that the innate immune response can be interfered by maternal protein restriction during early lactation [57]. Accordingly, nitric oxide production of peritoneal macrophages in low-protein offspring was lower than control offspring after a postweaning high-fat diet [58].…”

Maternal Serum Albumin Redox State Is Associated with Infant Birth Weight in Japanese Pregnant Women

“…The relationship between serum ALB redox state and birth weight of the offspring was also examined in an FGR model in rats. In order to simulate FGR, pregnant animals are normally placed on low-protein diets [ 11 , 12 , 13 ], or maintained under protein-energy restriction [ 14 , 15 , 16 , 17 ]. Protein-energy restriction was selected here in light of the above-mentioned observations that Japanese pregnant women would have insufficient energy intake as well as protein intake [ 3 , 20 ].…”

“…LBW delivery is highly related to neonatal mortality and morbidity [ 1 ], and fetal undernutrition can even inflict epigenetically negative impacts on the fetus, thereby increasing the risk of non-communicative diseases later in life [ 9 ]. This latter notion is known as the “developmental origins of health and disease (DOHad)” hypothesis [ 10 ], which has been robustly demonstrated by animal studies where dams were given low-protein diets [ 11 , 12 , 13 ], or maintained under energy-restricted conditions [ 14 , 15 , 16 , 17 ]. Notably, the incidence of LBW infants is overtly higher in Japan (9.4%) compared with the average of Organization for Economic Cooperation and Development (OECD) countries (6.5%) [ 6 ].…”

Developmental Programming of Fertility in Cattle—Is It a Cause for Concern?

“…T-cell formation takes place in the thymus and lymphopoiesis occurs in the spleen, which has a key role in immunoglobulin production, lymphocyte regulation and enhancing phagocytosis [ 116 , 117 ]. A maternal low protein diet during pregnancy in rats induced long-lasting alterations in adult male offspring in both thymic structure and lymphocyte maturation and selection processes [ 118 ] and disproportionately reduced the growth of the spleen [ 107 ]. This was supported by a study of IUGR human babies, which developed a disproportionately small thymus [ 119 ].…”