Effects of Poor Maternal Nutrition during Gestation on Bone Development and Mesenchymal Stem Cell Activity in Offspring

Abstract

Poor maternal nutrition impairs overall growth and development of offspring. These changes can significantly impact the general health and production efficiency of offspring. Specifically, poor maternal nutrition is known to reduce growth of bone and muscle, and increase adipose tissue. Mesenchymal stem cells (MSC) are multipotent stem cells which contribute to development of these tissues and are responsive to changes in the maternal environment. The main objective was to evaluate the effects of poor maternal nutirtion during gestation on bone and MSC function in offspring. Thirty-six ewes were fed 100%, 60%, or 140% of energy requirements [NRC, 1985] beginning at day 31 ± 1.3 of gestation. Lambs from ewes fed 100% (CON), 60% (RES) and 140% (OVER) were euthanized within 24 hours of birth (1 day; n = 18) or at 3 months of age (n = 15) and bone and MSC samples were collected. Dual X-ray absorptiometry was performed on bones obtained from day 1 and 3 months. Proliferation, differentiation, and metabolic activity were determined in the MSC isolated from lambs at day 1. Data were analyzed using mixed procedure in SAS. Maternal diet negatively affected offspring MSC by reducing proliferation 50% and reducing mitochondrial metabolic activity. Maternal diet did not alter MSC glycolytic activity or differentiation in culture. Maternal diet tended to decrease expression of P2Y purinoreceptor 1, but did not alter expression of other genes involved in MSC proliferation and differentiation. Maternal diet did not alter bone parameters in offspring. In conclusion, poor maternal diet may alter offspring growth through reduced MSC proliferation and metabolism. Further studies evaluating the potential molecular changes associated with altered proliferation and metabolism in MSC due to poor maternal nutrition are warranted.

CELL BIOLOGY SYMPOSIUM: METABOLIC RESPONSES TO STRESS: FROM ANIMAL TO CELL: Poor maternal nutrition during gestation: effects on offspring whole-body and tissue-specific metabolism in livestock species1,2

“…This diversion could be a potential mechanism by which poor maternal diet alters offspring growth and body composition (e.g., muscle, bone, and adipose; Devlin and Bouxsein, 2012) and metabolism. In offspring from both restrictedfed (60% of control) and overfed (140% of control) ewes during gestation, MSC proliferation was reduced by 50% (Pillai et al, 2016). In addition, MSC mitochondrial basal respiration and ATP production were decreased, suggesting a decreased basal metabolic activity.…”

“…Mesenchymal stem cells (MSC) are the key progenitor cells for several tissues including bone, muscle, and adipose. There is evidence that factors, such as maternal diet, negatively affect MSC metabolism and function (e.g., proliferation and differentiation; Boyle et al, 2016Boyle et al, , 2017Pillai et al, 2016), which are implicated in increased obesity or incidence of osteoporosis (Devlin and Bouxsein, 2012;Chen et al, 2016b). Mesenchymal stem cells are multipotent stem cells found in the bone marrow, as well as other tissues, including adipose.…”

“…In addition, MSC mitochondrial basal respiration and ATP production were decreased, suggesting a decreased basal metabolic activity. Maximal respiration and spare respiratory capacity were reduced in offspring from overfed ewes, and maximal respiration was reduced in offspring of restricted-fed ewes (Pillai et al, 2016). This suggests that the poor maternal diet restricts the ability of MSC to upregulate oxidative phosphorylation to meet any increase in energy demands.…”

Differentiation Potential of Mesenchymal Stem/Stromal Cells Is Altered by Intrauterine Growth Restriction

“…IUGR has been reported to affect cell growth and adipogenesis differentiation properties of stem cells (29,30), which may underlie altered developmental phenotype and predisposition to later disease in IUGR individuals. However, the impact of IUGR on MSC properties is still unclear.…”

>b<Efeito da nutrição energética em ovelhas durante a gestação sobre o desempenho de cordeiros na fase de terminação>/b<

“…A má nutrição materna durante a gestação não só tem um efeito direto sobre a disponibilidade de nutrientes da prole, mas também cria um ambiente de estresse que pode levar a efeitos em longo prazo ou permanentes no desenvolvimento tecidual (DEVLIN et al, 2012, PILLAI et al, 2016DU et al, 2011). A densidade mineral óssea pode ser estimada através de métodos invasivos e não invasivos.…”