Maternal Fibroblast Growth Factor 21 Levels Decrease during Early Pregnancy in Normotensive Pregnant Women but Are Higher in Preeclamptic Women—A Longitudinal Study

Abstract

(1) Background: Fibroblast growth factor 21 (FGF-21) is an endocrine factor involved in glucose and lipid metabolism that exerts pleiotropic effects. The aim of this study was to investigate the serum FGF-21 profile in healthy and mild preeclamptic pregnant women at each trimester of pregnancy; (2) Methods: Serum FGF-21 levels were determined by ELISA in a nested case-control study within a longitudinal cohort study that included healthy (n = 54) and mild preeclamptic (n = 20) pregnant women, women at three months after delivery (n = 20) and eumenorrheic women during the menstrual cycle (n = 20); (3) Results: FGF-21 levels were significantly lower in the mid-luteal phase compared to the early follicular phase of the menstrual cycle in eumenorrheic women (p < 0.01). Maternal levels of FGF-21 were significantly lower in the first and second trimesters and peaked during the third trimester in healthy pregnant women (p < 0.01). Serum levels of FGF-21 in healthy pregnant were significantly lower in the first and second trimester of pregnancy compared with the follicular phase of the menstrual cycle and postpartum (p < 0.01). Serum FGF-21 levels were significantly higher in preeclamptic compared to healthy pregnant women during pregnancy (p < 0.01); (4) Conclusions: These results suggest that a peak of FGF-21 towards the end of pregnancy in healthy pregnancy and higher levels in preeclamptic women might play a critical role that contributes to protecting against the negatives effects of high concentrations of non-esterified fatty acids (NEFA) and hypertensive disorder. Furthermore, FGF-21 might play an important role in reproductive function in healthy eumenorrheic women during the menstrual cycle.

Fibroblast Growth Factor 21 Has a Diverse Role in Energetic and Reproductive Physiological Functions of Female Beef Cattle

“…This study has demonstrated for the first time that FGF21 is not divergent between prepubertal and postpubertal heifers nor across the phases of the estrous cycle of beef heifers. Our finding that the circulating concentration of FGF21 is not correlated with the circulating concentration of progesterone in beef heifers contradicts the findings of others [20] that observed a negative correlation between circulating FGF21 and progesterone in women. Another report [21] also supports these findings [20] indirectly by presenting that the activation of the hepatic estrogen receptor-α increases energy expenditure by stimulating the production of FGF21 in mice.…”

“…Our finding that the circulating concentration of FGF21 is not correlated with the circulating concentration of progesterone in beef heifers contradicts the findings of others [20] that observed a negative correlation between circulating FGF21 and progesterone in women. Another report [21] also supports these findings [20] indirectly by presenting that the activation of the hepatic estrogen receptor-α increases energy expenditure by stimulating the production of FGF21 in mice. The differences in findings between the aforementioned and current report are potentially attributed to differences in species, divergent regulatory mechanisms of action, or differences in lag time to observable change in circulatory FGF21 between models.…”

The causal role of circulating immunity‐inflammation in preeclampsia: A Mendelian randomization

“…Previous cross‐sectional investigations have shown a substantial rise in maternal FGF‐21 levels in women with preeclampsia in comparison to pregnant women who do not have hypertension 25 . Longitudinal cohort research has shown that serum FGF‐21 levels are markedly elevated in pregnant women with preeclampsia as compared to healthy pregnant women with normal blood pressure during all three trimesters of pregnancy 26 . FGF21 level was shown to be a risk factor for PE in research employing binary logistic regression analysis 27 .…”

“… 25 Longitudinal cohort research has shown that serum FGF‐21 levels are markedly elevated in pregnant women with preeclampsia as compared to healthy pregnant women with normal blood pressure during all three trimesters of pregnancy. 26 FGF21 level was shown to be a risk factor for PE in research employing binary logistic regression analysis. 27 In a community sample, FGF21 was shown to be independently related to hypertension.…”