Network analysis of core symptom changes in Chinese patients undergoing radical prostatectomy for prostate cancer: a longitudinal study.

The conceptus is dependent upon the mother for provision of nutrients, including essential amino acids. As the primary communication organ with the mother, the placenta receives all nutrients and gases from underlying uterine blood vessels and returns fetal waste into maternal circulation for excretion. The placenta also relays the products received from the mother to the developing fetal organs. Amino acids are the building blocks for peptides and longer protein molecules. Placental deficiency in amino acid transport results in suppressed fetal growth [,]. The amino acid tryptophan (Trp) serves as the precursor for serotonin (5-HT). All Trp must be acquired through the diet with corn and sorghum providing minimal amounts of this essential amino acid []. Thus, in countries where such foods are the main sources of nutrition, individuals are prone to Trp deficiencies. There are other etiologies for reduced Trp levels, including Hartnup disease—a genetic condition causing reduced absorption of Trp in the gastrointestinal tract and reabsorption in the renal tubules []—Crohn’s disease [], and preeclampsia []. In pregnant women, Trp reductions might result in harmful effects to the mother and her unborn offspring. Female mice on a completely deficient Trp diet bred to male mice show impaired decidualization response at day 5 and no implantation sites by day 8 []. Findings reveal that complete Trp deficient mice are unable to become pregnant. However, no differences in uterine receptivity molecules were noted between a reduced Trp group and control group of female mice []. While mice on the reduced Trp diet can become pregnant, concern remains as to how this might impact their developing conceptus. 5-HT is critical for normal placental and fetal development [], thus the importance of its precursor, Trp, in pregnancy can be extrapolated and was the focus of a recent review article []. The article highlighted a cohort study with over 1000 female participants showing that elevation in maternal 5-hydroxytryptophan (5HTP) that might result in 5-HT deficiency is associated with small fetal size and potentially fetal growth restriction (defined as estimated fetal weight less than the tenth percentile) []. It also included various mouse studies. One study demonstrated that maternal imbalances of 5-HT lead to teratogenic effects in the conceptus, including congenital malformations of the central nervous system [,,,]. In fact, injection of 5-HT into pregnant mice during the pre-implantation period leads to miscarriage [,,,]. In mice, uterine inflammation due to intra-amniotic injection of bacterial lipopolysaccharide (LPS) downregulates tryptophan hydroxylase (TPH) expression in the placenta with concomitant reduction in 5-HT levels []. This treatment also suppresses TPH expression but increases monoamine oxidase expression in the fetal brain with a resultant decreased level of 5-HT [].