Chronic developmental hypoxia alters mitochondrial oxidative capacity and reactive oxygen species production in the fetal rat heart in a sex-dependent manner.

Insufficient oxygen supply (hypoxia) during fetal development leads to cardiac remodeling and a predisposition to cardiovascular disease in later life. Previous work has shown hypoxia causes oxidative stress in the fetal heart and alters the activity and expression of mitochondrial proteins in a sex-dependent manner. However, the functional effects of these modifications on mitochondrial respiration remain unknown. Furthermore, while maternal antioxidant treatments are emerging as a promising new strategy to protect the hypoxic fetus, whether these treatments convey similar protection to cardiac mitochondria in the male or female fetus has not been investigated. Therefore, using an established rat model, we measured the sex-dependent effects of gestational hypoxia and maternal melatonin treatment on fetal cardiac mitochondrial respiration, reactive oxygen species (ROS) production, and lipid peroxidation. Pregnant Wistar rats were subjected to normoxia or hypoxia (13% oxygen) during gestational days (GDs) 6-20 (term ~22 days) with or without melatonin treatment (5 µg/ml in maternal drinking water). On GD 20, mitochondrial aerobic respiration and H2 O2 production were measured in fetal heart tissue, together with lipid peroxidation and citrate synthase (CS) activity. Gestational hypoxia reduced maternal body weight gain (p < .01) and increased placental weight (p < .05) but had no effect on fetal weight or litter size. Cardiac mitochondria from male but not female fetuses of hypoxic pregnancy had reduced respiratory capacity at Complex II (CII) (p < .05), and an increase in H2 O2 production/O2 consumption (p < .05) without any changes in lipid peroxidation. CS activity was also unchanged in both sexes. Despite maternal melatonin treatment increasing maternal and fetal plasma melatonin concentration (p < .001), melatonin treatment had no effect on any of the mitochondrial parameters investigated. To conclude, we show that gestational hypoxia leads to ROS generation from the mitochondrial electron transport chain and affects fetal cardiac mitochondrial respiration in a sex-dependent manner. We also show that maternal melatonin treatment had no effect on these relationships, which has implications for the development of future therapies for hypoxic pregnancies.

Administration of Cinnamon and Lagersroemia speciosa Extract on Lipid Profile of Polycystic Ovarian Syndrome Women with High Body Mass Index.

BACKGROUND: Hyperinsulinemia, a common feature in PCOS, have been found to contribute to metabolic disturbance, such as dyslipidaemia and diabetes mellitus type 2. Oral anti-diabetic medications have been prescribed to alleviate this effect. We sought to fnd whether DLBS3233, an insulin sensitizer, could alleviate dyslipidaemia in women with PCOS with high BMI. AIM: This study aimed to investigate the effect of DLBS3233, an herbal combination of C burmanii and L spesiosa extract, on lipid profle, insulin resistance, and free testosterone of women with PCOS with high BMI. STUDY SETTING AND DESIGN: This was a controlled trial conducted in Dr. Cipto Mangunkusumo Hospital, Jakarta, and Dr Hasan Sadikin Hospital, Bandung, Indonesia. MATERIALS AND METHODS: A controlled trial was conducted on 62 volunteers diagnosed with PCOS according to Rotterdam criteria and exhibited insulin resistance as signifed by HOMA-IR > 2.0; baseline lipid profile (LDL, HDL, Triglyceride and Total cholesterol) and free testosterone concentration were obtained. Participants were given 100 mg of DLBS3233 in the morning, and volunteers were followed up monthly, with laboratory tests conducted at the third and sixth months. Data were analysed through intention-to-treat analysis, separating high BMI (≥25 kg/m2) subjects. STATISTICAL ANALYSIS: Repeated-measures model. RESULTS: DLBS3233 improved lipid profle and insulin sensitivity by reducing triglycerides, HOMA-IR, and free testosterone in subjects with high BMI. Limitations and Implications: The current study does not compare the effect of DLBS3233 with a control group. A larger study with a proper control group would have to be conducted to have more conclusive results. CONCLUSION: This study showed that DLBS3233 holds promise as a novel therapy to improve lipid profle for women with PCOS.

Correlation of Anti-Mullerian Hormone Level and Antral Follicle Count with Oocyte Number in A Fixed-Dose Controlled Ovarian Hyperstimulation of Patients of In Vitro Fertilization Program.

BACKGROUND: This study was conducted to determine the correlation of anti-Mullerian hormone (AMH) level and antral follicle count (AFC) with oocyte count in women who had received controlled ovarian hyperstimulation in an in vitro fertilization (IVF) program. MATERIALS AND METHODS: We retrospectively gathered the data of 42 patients who underwent IVF during 2005-2017 at Aster Clinic in Dr. Hasan Sadikin Hospital and Bandung Fertility Center Limijati Hospital, Indonesia. Details of the subjects such as identity, characteristics, history of illness, history of previous therapy, levels of ovarian reserve markers examined (AFC and AMH), follicle-stimulating hormone (FSH) dose given, and number of oocytes produced were recorded. RESULTS: A significant positive correlation between AMH (P≤0.001, r=0.530), AFC (P≤0.001, r=0.687), and AMHAFC combination (P≤0.001, r=0.652), and the number of oocytes was found at the FSH dose of 225 IU. CONCLUSION: AFC and AMH are able to reliably predict ovarian response to FSH.