Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Mar;243(6):525-533.
doi: 10.1177/1535370218758275. Epub 2018 Feb 22.

Impacts of Maternal Dietary Protein Intake on Fetal Survival, Growth, and Development

Affiliations
Free PMC article
Review

Impacts of Maternal Dietary Protein Intake on Fetal Survival, Growth, and Development

Cassandra M Herring et al. Exp Biol Med (Maywood). .
Free PMC article

Abstract

Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H2S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new, effective means to improve embryonic/fetal survival and growth in mammals.

Keywords: Protein; fetus; growth; nutrition; placenta; reproduction.

Figures

Figure 1.
Figure 1.
Ammonia toxicity decreases embryonic and fetal survival, growth, and development. Ammonia, H2S, and homocysteine are products from AA oxidation. High levels of ammonia are toxic to the developing embryo/fetus due to (1) oxidative stress resulting from ammonia pulling glutamate away from glutathione synthesis to produce glutamine, which is an inhibitor of nitric oxide (NO) generation from arginine. H2S and homocysteine also contribute to oxidative stress, which reduces progesterone production and release by the ovaries. (2) Ammonia binds a proton to form ammonium ion, which increases intracellular pH. (3) Ammonia draws α-ketoglutarate from the Krebs cycle to form glutamate, therefore inhibiting the Krebs cycle and reducing ATP production. (4) Increased production of glutamine from ammonia inhibits NO production from arginine by endothelial cells, which decreases blood flow (including utero-placental blood flow) and nutrient transport, leading to a decrease in uterine secretion as well as hypoxia in the conceptus. These consequences result in decreased embryonic/fetal survival, growth, and development. GDH: glutamate dehydrogenase.
Figure 2.
Figure 2.
Adverse consequences of low maternal dietary intake of protein or amino acids (AAs) during pregnancy. Low maternal dietary intake of protein and AAs leads to many negative effects, such as impaired secretion of histotroph; impaired embryonic development; impaired mechanistic target of rapamycin (mTOR) cell signaling in mother and conceptus; reduced placental angiogenesis, growth and development; reduced supply of nutrients from mother to fetus; inducing oxidative stress in mother and conceptus; impaired absorption and transport of lipids, lipid-soluble vitamins and microminerals (e.g. iron and zinc); and induction of deficiencies of multiple nutrients. These consequences result in embryonic/fetal death, loss of pregnancy, intrauterine growth restriction and poor maternal health.
Figure 3.
Figure 3.
Adverse consequences of high maternal dietary intake of protein or amino acids (AAs) during pregnancy. High maternal dietary intake of protein and AAs causes an increase in ammonia, homocysteine and hydrogen sulfide (H2S) and an acid-base imbalance. Under normal conditions (represented by a dashed arrow), ammonia is catabolized into urea, glutamine and glutamate, homocysteine is recycled into methionine, hydrogen sulfide is excreted through the lungs and skin, and acid-base homeostasis is regulated by the lungs and kidneys. However, excessive intake of protein or AAs dysregulates these processes and results in embryonic/fetal death, loss of pregnancy, intrauterine growth restriction, and poor maternal health. 5-MTF: N5-methyl-tetrahydrofolate; Vit B6: vitamin B6.

Similar articles

See all similar articles

Cited by 12 articles

See all "Cited by" articles

Publication types

Substances

Feedback