Role of Dietary Amino Acids and Nutrient Sensing System in Pregnancy Associated Disorders

Abstract

Defective implantation is related to pregnancy-associated disorders such as spontaneous miscarriage, intrauterine fetal growth restriction and others. Several factors proclaimed to be involved such as physiological, nutritional, environmental and managemental that leads to cause oxidative stress. Overloading of free radicals promotes oxidative stress, and the internal body system could not combat its ability to encounter the damaging effects and subsequently leading to pregnancy-related disorders. During pregnancy, essential amino acids display important role for optimum fetal growth and other necessary functions for continuing fruitful pregnancy. In this context, dietary amino acids have received much attention regarding the nutritional concerns during pregnancy. Arginine, glutamine, tryptophan and taurine play a crucial role in fetal growth, development and survival while ornithine and proline are important players for the regulation of gene expression, protein synthesis and angiogenesis. Moreover, amino acids also stimulate the mammalian target of rapamycin (mTOR) signaling pathway which plays a central role in the synthesis of proteins in placenta, uterus and fetus. This review article explores the significances of dietary amino acids in pregnancy development, regulation of nutrient-sensing pathways such as mTOR, peroxisome proliferator-activated receptors (PPARs), insulin/insulin-like growth factor signaling pathway (IIS) and 5' adenosine monophosphate-activated protein kinase (AMPK) which exhibit important role in reproduction and its related problems. In addition, the antioxidant function of dietary amino acids against oxidative stress triggering pregnancy disorders and their possible outcomes will also be enlightened. Dietary supplementation of amino acids during pregnancy could help mitigate reproductive disorders and thereby improving fertility in animals as well as humans.

Keywords: dietary amino acids; oxidative stress; pregnancy; reproductive disorders; signaling pathways.

FIGURE 1

Transportation of amino acids to placenta via mTOR signaling pathway Schematic diagram of mTOR pathway of placenta act as a nutrient sensor. It co-ordinates nutrient and growth factors to modulate transfer of maternal nutrients to the fetal circulation. MTORC1 modulates trafficking of AA transports by employing differential ubiquitination mediated by NEDD4-2. Inhibition of NEDD4-2 leads to enhanced localization of AA transporters in the plasma membrane.

FIGURE 2

Role of IIS signaling pathway in reproduction and its longevity Schematic diagram elicits that IIS is actively involved in reproductive function and lifespan in C. elegans D. melanogaster or mice. In brief, ILP receptor binds with transmembrane for IIS tyrosine kinase receptor (DAF-2 in C. elegans), that autophosphorylates and recruits and finally stimulating key substrates, through different channels directly or via receptor substrate intermediate. Once the simulation of PI3k/Akt branch of IIS (left) takes place, it converts PI(4,5)P2 into second messenger PI(3,4,5)P3; which are negatively regulated by phospholipid phosphatases such as the PI3-phosphatase PTEN. Activation of PI (3,4,5) P3 causes recruitment 3-phosphoinositide–dependent protein kinase-1 (PDPK1) and its substrate, Akt/protein kinase B. Once the Akt pathway stimulates different cellular substrates not mentioned here, consisting of Rab-GTPase–activating protein AS160, glycogen synthase kinase-3, and TSC1/TSC2. The Akt is a key regulator of FoxO transcription factor (DAF-16 in C. elegans); that phosphorylates by Akt resulting in inhibition of transcriptional activity through bringing Akt back into the cytoplasm. On the other hand, Ras/MAPK branch of IIS (right), binds with adaptor protein Grb2 and the guanine nucleotide exchange protein Son of sevenless (SOS) to the activated IIS receptor, either directly or through docking protein, and hence it allows SOS to catalyze from inactive GDP-bound Ras to active GTP-bound Ras. The stimulation of small GTPase Ras activates of the serine/threonine kinase Raf, that leads to stepwise phosphorylation and activation of MEK1/MEK2 and then ERK1/ERK2. While the stimulation of ERK1 phosphorylates numerous cellular and nuclear substrates not display here, RSK and ELK1. Green color shows phosphorylation (kinase activity), whereas, (orange color) highlight dephosphorylating (phosphatase activity).

FIGURE 3

Beneficial effects of dietary supplementation of amino acids.

FIGURE 4

Regulation of energy homeostasis, reproductive function by nutrient sensing system in response to nutrient availability.