Coffee intake leads to preeclampsia-like syndromes in susceptible pregnant rats

Abstract

Coffee is one of the most popular beverages worldwide, and there is an increasing concern of the health risk of coffee consumption in pregnancy. Preeclampsia (PE) is a serious pregnancy disease that causes elevated blood pressure and proteinuria in pregnant women and growth restriction of fetuses due to poorly developed placental vasculature. The aim of our study is to investigate the possible effect of coffee intake during pregnancy in rats with potential underlying vasculature conditions. The endothelial nitric oxide synthase inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) at a high dose (125 mg/kg/d) was used to induce PE in pregnant rats, which were used as the positive control group. In addition, low-dose L-NAME (10 mg/kg/d) was used to simulate the compromised placental vasculature function in pregnant rats. Coffee was given together with low-dose L-NAME to the pregnant rats from gestational day 10.5-18.5. Our results show that the pregnant rats treated with low-dose L-NAME + coffee, but not low-dose L-NAME alone, developed PE symptoms such as prominent fetal growth restriction, hypertension, and proteinuria. Therefore, our findings suggest that coffee intake during pregnancy may cause an increased risk of PE in susceptible women.

Keywords: Coffee; Fetus; Preeclampsia; Pregnancy.

Fig. 1.

Fetus development in pregnant rats treated with L-NAME and/or Coffee. (a) Total number of fetuses, (b) number of malformation fetuses, (c) Weight of fetuses, (d) weight of placenta. C: Control group, L-H: L-NAME high-dose group, L-L: L-NAME low-dose group, L-L + Cof: L-NAME low-dose + Coffee group. Results are shown as mean ± SD. For (a) and (b), Control group: n = 8, L-NAME high-dose group: n = 11, L-NAME low-dose group: n = 7, L-NAME low-dose + Coffee group: n = 8; For (c) and (d), Control group: n = 52, L-NAME high-dose group: n = 96, L-NAME low-dose group: n = 44, L-NAME low-dose + Coffee group: n = 54., *P < 0.05; **P < 0.01 compared to control group; ^##P < 0.01 compared between the two indicated groups.

Fig. 2.

Systolic blood pressure (SBP) and renal functions of pregnant rats treated with L-NAME and/or Coffee. (a) The change in SBP on GD18.5 compared to GD9.5, (b) Urinary protein level indicated by urinary albumin (U-Ab)/urinary creatinine (U-Crea), (c) Serum creatine, (d) serum sFlt-1 level in pregnant rats. C: Control group, L-H: L-NAME high-dose group, L-L: L-NAME low-dose group, L-L + Cof: L-NAME low-dose + Coffee group. Results are shown as mean ± SD. Control group: n = 8, L-NAME high-dose group: n = 11, L-NAME low-dose group: n = 7, L-NAME low-dose + Coffee group: n = 8. *P < 0.05; **P < 0.01 compared to control group; ^#P < 0.05; ^##P < 0.01 compared between the two indicated groups.

Fig. 3.

Changes of placenta structure in pregnant rats. Placental histology in hematoxylin/eosin-stained sections from the control group (a), the L-NAME high-dose group (b), the L-NAME low-dose group (c), and the L-NAME low-dose + Coffee group (d). The dotted line divides the placental structure into three parts. D, decidua, JZ, junctional zone; L, labyrinth. Scale bars: 100 μm. (e) The relative thickness of the junctional zone (JZ). Results are shown as mean ± SD. Control group: n = 8, L-NAME high-dose group: n = 11, L-NAME low-dose group: n = 7, L-NAME low-dose + Coffee group: n = 8. **P < 0.01 compared to control group; ^##P < 0.01 compared between the two indicated groups.

Fig. 4.

Comparison of vascular network distribution in placenta. Cross sections of labyrinth region of placenta in the control group (a), the L-NAME high-dose group (b), the L-NAME low-dose group (c), and the L-NAME low-dose + Coffee group (d). Scale bars: 100 μm. (e) The arterial diameter in the labyrinth region. Results are shown as mean ± SD. Control group: n = 8, L-NAME high-dose group: n = 11, L-NAME low-dose group: n = 7, L-NAME low-dose + Coffee group: n = 8. *P < 0.05; **P < 0.01 compared to control group.

Fig. 5.

Comparison of eNOS expression in placenta. Immunohistochemical staining of placenta with eNOS antibody in the control group (a), the L-NAME high-dose group (b), the L-NAME low-dose group (c), and the L-NAME low-dose + Coffee group (d), Scale bar =100 μm. (e) The quantitative analysis of the positive area (%). Results are shown as mean ± SD. Control group: n = 8, L-NAME high-dose group: n = 11, L-NAME low-dose group: n = 7, L-NAME low-dose + Coffee group: n = 8. *P < 0.05; **P < 0.01 compared to control group, ^#P < 0.05 compared between the two indicated groups.