List of Gene Ontology (GO) terms that were significantly enriched (FDR ≤ 0.01) with differentially expressed genes (DEG) detected between wild-type (WT) <i>vs</i>. Knock-out mammary glands on day 10 of lactation.

<p>The graph shows the term name, the total number of genes within each term, and the number of genes up-regulated (green) and down-regulated (yellow) in the knock-out compared to the wild-type. Knock-out = Tryptophan hydroxylase (<i>Tph1</i>) deficient mice.</p

Functional characterization of the 204 most significant genes (FDR ≤ 0.01 and fold change ≥ 2) detected in the mouse mammary gland on day 10 of lactation between WT <i>vs</i>. RC dams.

<p>WT = wild-type mice; RC = Rescue mice (<i>Tph1</i> KO + 100 mg/kg daily injections of 5-hydroxytryptophan). Gene symbols that are underlined denote genes downregulated in the mammary gland of RC dams compared to WT dams.</p><p>These are functional terms that were detected exclusively in this specific comparison.</p

Functional characterization of the 97 most significant genes (FDR ≤ 0.01 and fold change ≥ 2) detected in the mouse mammary gland on day 10 of lactation between WT <i>vs</i>. KO dams.

<p>WT = wild-type mice; KO = Tryptophan hydroxylase (<i>Tph1</i>) deficient mice. Gene symbols that are underlined denote genes downregulated in the mammary gland of KO dams compared to WT dams.</p><p>These are functional terms that were detected exclusively in this specific comparison.</p

List of Gene Ontology (GO) terms that were significantly enriched (FDR ≤ 0.01) with differentially expressed genes (DEG) detected between wild-type (WT) <i>vs</i>. Rescue mammary gland on day 10 of lactation.

<p>The graph shows the term name, the total number of genes within each term, and the number of genes up-regulated (green) and down-regulated (yellow) in the Rescue compared to the wild-type. Rescue = Tryptophan hydroxylase (<i>Tph1</i>) knock-out + 100 mg/kg daily injections of 5-hydroxytryptophan.</p

Validation of overall gene expression.

<p>Fold changes of four differentially expressed genes measured by RNA-Seq (blue) versus qRT-PCR (orange). Genes period circadian clock 2 (Per2), a novel transcript unit [Chr5:30,208,00730,212,059] (NTU), and G protein-coupled receptor 113 (Gpr113) were statistically upregulated in the mammary gland of RC dams while gene GLIS family zinc finger 3 (Glis3) was statistically upregulated in the mammary gland of WT dams.</p

List of Gene Ontology (GO) biological process terms that were significantly enriched (FDR ≤ 0.01) with differentially expressed genes (DEG) detected simultaneously in both pairwise comparisons involving the wild-type (WT) mammary glands on day 10 of lactation: WT <i>vs</i>. Knock-out (A) and WT <i>vs</i>. Rescue (B).

<p>The graph shows the term name, the total number of genes within each term, and the number of genes up-regulated (green) and down-regulated (yellow) in the knock-out or rescue compared to the WT. Knock-out = Tryptophan hydroxylase (<i>Tph1</i>) deficient mice; Rescue = <i>Tph1</i> knock-out + 100 mg/kg daily injections of 5-hydroxytryptophan.</p

Comparison of overall gene expression between the three treatment groups.

<p>Mammary gland samples belong to wild-type dams (WT), Tryptophan hydroxylase (<i>Tph1</i>) deficient dams (serotonin deficient; KO), and <i>Tph1</i> deficient dams injected daily with 5-hydroxytryptophan (RC). (<b>A</b>) The bar graph shows the number of genes upregulated in each group for each of the three pairwise comparisons. The numbers represent the total number of differentially expressed genes (DEG) at 5% FDR (and at 1% FDR in parenthesis). (<b>B</b>) The Venn diagram shows the overlap between genes that showed significant differential expression at 5% FDR in each of the three pairwise comparisons.</p

Functional characterization of the 62 most significant genes (FDR ≤ 0.01 and fold change ≥ 2) detected simultaneously in the mouse mammary gland on day 10 of lactation between WT <i>vs</i>. KO dams and WT <i>vs</i>. RC dams.

<p>WT = wild-type mice; KO = Tryptophan hydroxylase (<i>Tph1</i>) deficient mice; RC = Rescue mice (<i>Tph1</i> KO + 100 mg/kg daily injections of 5-hydroxytryptophan). Gene symbols that are underlined denote genes downregulated in the mammary gland of KO and RC dams compared to WT dams.</p><p>Functional characterization of the 62 most significant genes (FDR ≤ 0.01 and fold change ≥ 2) detected simultaneously in the mouse mammary gland on day 10 of lactation between WT <i>vs</i>. KO dams and WT <i>vs</i>. RC dams.</p

Medical Subject Headings (MeSH) terms that were significantly enriched (FDR ≤ 0.01) with differentially expressed genes detected in the mammary gland on day 10 of lactation for the following pairwise comparisons: WT <i>vs</i>. KO and WT <i>vs</i>. RC.

<p>Medical Subject Headings (MeSH) terms that were significantly enriched (FDR ≤ 0.01) with differentially expressed genes detected in the mammary gland on day 10 of lactation for the following pairwise comparisons: WT <i>vs</i>. KO and WT <i>vs</i>. RC.</p

Ablation of Tph1 gene in dams decreased circulating serotonin and calcium on day 1 and 10 of lactation.

<p>Wild-type (WT) mouse dams were given saline and Tryptophan hydroxylase knock-out dams given either saline (<i>Tph1^−/−</i>) or daily injections of exogenous 5-HTP (100 mg/kg; <i>Tph1^−/−</i> (5-HTP)), from pregnancy d20 to lactation d10. (A) Serum serotonin (d1 and d10 of lactation) and (B) mammary serotonin concentrations (d10 of lactation). (C) Serum calcium concentration (d1 and d10 of lactation). All values are the mean ± SEM (n = 7). Groups with different letters are significantly different (<i>P</i><0.05).</p