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.

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.

Introduction Gestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity. Methods and results Herein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. Conclusions Placental mitochondrial fusion is enhanced in GDM, possibly as a compensatory response to maternal and fetal metabolic derangements. Alterations in placental insulin exposure and sphingolipid metabolism are among potential contributing factors. Overall, our results suggest that GDM has profound impacts on placental mitochondrial dynamics and metabolism, with plausible implications for the short-term and long-term health of the offspring.

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.

This editorial provides a brief overview of the importance of pilot or feasibility trials or studies, the challenges with current practices in their conduct and reporting, an introduction to the Consolidated Standards of Reporting Trials (CONSORT) extension to pilot trials aimed at improving their reporting, along with some key resources on aspects related to pilot and feasibility studies.

In the present study, we compared the effect of diabetic pregnancy on the rectus abdominis muscle (RAM) in humans and rats. We hypothesized that our animal model could provide valuable information about alterations in the RAM of women with Gestational Diabetes (GDM). Newborns female rats (n = 10/group) were administered streptozotocin (100 mg/kg body weight) subcutaneously and were mated on reaching adulthood, to develop the mild hyperglycemic pregnant (MHP) rat model. At the end of pregnancy, the mothers were sacrificed, and the RAM tissue was collected. Pregnant women without GDM (non-GDM group; n = 10) and those diagnosed with GDM (GDM group; n = 8) and undergoing treatment were recruited, and RAM samples were obtained at C-section. The RAM architecture and the distribution of the fast and slow fibers and collagen were studied by immunohistochemistry. No statistically significant differences in the maternal and fetal characters were observed between the groups in both rats and women. However, significant changes in RAM architecture were observed. Diabetes in pregnancy increased the abundance of slow fibers and decreased fast fiber number and area in both rats and women. A decrease in collagen distribution was observed in GDM women; however, a similar change was not observed in the MHP rats. Our results indicated that pregnancy- associated diabetes- induced similar structural adaptations in the RAM of women and rats with slight alterations in fiber type number and area. These findings suggest that the MHP rat model can be used for studying the effects of pregnancy-associated diabetes on the fiber structure of RAM.