Fig. 2: Administration of 5HTP, the immediate precursor of 5HT, to pregnant rodents reduces adrenal medulla in the progeny.
From: Serotonin limits generation of chromaffin cells during adrenal organ development
a 5HTP was administered to pregnant BalbC mice at E10.5–E13.5. The embryos are collected at E14.5 for the HPLC-based analysis of 5HT. b Concentration of 5HT in the adrenal glands and surrounding tissues (left) and placentas (right) at E14.5 after 5HTP administration at E10.5–E13.5 stage. Unpaired double-sided t-test p-value ** < 0.001, biological n = 9. c Adrenal glands from E14.5 embryos release 5HT into the surrounding medium measured by HPLC-ED. Note: kidneys, used as a control tissue, do not release 5HT. Unpaired double-sided t-test p-value * < 0.05, **= 0.005, biological n = 6. d 5HTP was administered to pregnant Wistar rats at E11.5–E15.5 followed by embryo collection at E15.5 and analysis by X-ray computed microtomography (microCT). e microCT X-ray reconstruction of adrenal glands and kidney volume from E15.5 rat embryos obtained from females in control and 5HTP-treated groups. Volumes of the organs in µm3 (×105). f Adrenal gland volume normalized to the volume of adjacent kidneys. Biological n = 4. Unpaired double-sided t-test p-value ** < 0.005. g Section areas of adrenal gland, adrenal medulla and adrenal cortex based on immunohistochemistry analysis with anti-TH immunostaining. Unpaired double-sided t-test p-value ns > 0.05, * < 0.05, biological n = 4 (control), 5 (5HTP). h Prenatal 5HTP exposure at the time of “bridge” cell differentiation (E11.5–E15.5 in rats and E10.5–E14.5 in mice) causes the decrease of postnatal adrenal medulla size in P30 animals, which was greater than decreased induced by 5HTP exposure after the time of “bridge” cell differentiation (E15.5–E18.5 in rats and E14.5–E15.5 in mice). Green line in all violin plots—the median, red lines—quartiles. One-way ANOVA test with Dunnett’s multiple comparison test **p = 0.0017, ***p = 0.0002, ****p < 0.0001, biological n (adrenal gland) = 24 (control male rat), 19 (E11.5–E15.5 male rat), 20 (E15.5–E18.5 male rat), 35 (control female mice), 16 (E11.5–E15.5 female rat), 20 (E15.5–E18.5 female rat), 40 (control male mice), 24 (E10.5–E14.5 male mice), 27 (E14.5–E15.5 male mice), 35 (control female mice), 18 (E10.5–E14.5 and E14.5–E15.5 female mice). For all experiments normality is checked with Shapiro–Wilk test. AG: adrenal gland, Kid: kidney, PG and ZO: paraganglia and organ of Zuckerkandl, DA: dorsal aorta.
