We analyzed the perinatal outcome of 1,086 pregnancies classified according to the response to the 3-hour 100-gram glucose tolerance test and the diurnal glycemic profile into the Rudge groups corresponding to control pregnant women, class A gestational diabetic women, class A/B to FRH pregnant women and women with daily hyperglycemia. Despite treatment, the diabetic pregnant women and those with daily hyperglycemia presented higher mean blood glucose levels compared to controls (76.6 ± 10.2 mg/dl). The pregnancies complicated by diabetes and by daily hyperglycemia were characterized by a high incidence of prematurity, macrosomia, large for gestational age newborn infants, malformation and fetal and neonatal death, with consequent perinatal mortality. The perinatal mortality of women with daily hyperglycemia was 10 times higher than that of the controls and was similar to that of the diabetic patients. These adverse perinatal results emphasize the need for the diagnosis and control of intrauterine hyperglycemia both in diabetic pregnant women and in women with an altered diurnal glycemic profile.

Mitochondria are in a constant balance of fusing and dividing in response to cellular cues. Fusion creates healthy mitochondria, whereas fission results in removal of non-functional organelles. Changes in mitochondrial dynamics typify several human diseases. However, the contribution of mitochondrial dynamics to preeclampsia, a hypertensive disorder of pregnancy characterized by placental cell autophagy and death, remains unknown. Herein, we show that the mitochondrial dynamic balance in preeclamptic placentae is tilted toward fission (increased DRP1 expression/activation and decreased OPA1 expression). Increased phosphorylation of DRP1 (p-DRP1) in mitochondrial isolates from preeclamptic placentae and transmission electron microscopy corroborated augmented mitochondrial fragmentation in cytotrophoblast cells of PE placentae. Increased fission was accompanied by build-up of ceramides (CERs) in mitochondria from preeclamptic placentae relative to controls. Treatment of human choriocarcinoma JEG3 cells and primary isolated cytrophoblast cells with CER 16:0 enhanced mitochondrial fission. Loss- and gain-of-function experiments showed that Bcl-2 member BOK, whose expression is increased by CER, positively regulated p-DRP1/DRP1 and MFN2 expression, and localized mitochondrial fission events to the ER/MAM compartments. We also identified that the BH3 and transmembrane domains of BOK were vital for BOK regulation of fission. Moreover, we found that full-length PTEN-induced putative kinase 1 (PINK1) and Parkin, were elevated in mitochondria from PE placentae, implicating mitophagy as the process that degrades excess mitochondria fragments produced from CER/BOK-induced fission in preeclampsia. In summary, our study uncovered a novel CER/BOK-induced regulation of mitochondrial fission and its functional consequence for heightened trophoblast cell autophagy in preeclampsia.

The present study reviews the possible role of Se status during pregnancy regarding adverse pregnancy outcomes, with emphasis on those related to diminished antioxidant activity and increased oxidative stress. Studies have reported that Se could play an important role in adverse outcomes such as miscarriages, neural tube defects, diaphragmatic hernia, premature birth, low birth weight, pre-eclampsia, glucose intolerance and gestational diabetes. Also, low Se status has been associated with adverse outcomes among HIV-infected pregnant women and their offspring. Nevertheless, the function of Se in the aetiology of pregnancy complications is yet to be elucidated. Available evidence presents the following limitations: most study designs do not allow conclusions about causal relationships; study populations, selection of subjects, research setting, procedures for defining sample size and analytical methods are often poorly described; many studies fail to adjust for important confounding variables. In addition, population studies assessing the relationship between Se intake during pregnancy and health outcomes are scarce. Further research is still needed to clarify the role of Se status in adverse pregnancy outcomes, especially those related to augmented oxidative stress.