Diminished ovarian reserve (DOR) is characterized by the depletion of the ovarian pool, which leads to reductions in oocyte quality and quantity. Studies have suggested that ovarian reserve or ovarian aging is tightly related to apoptosis. However, the cell death mechanism is not comprehensively understood. Parthanatos, a type of poly [ADP-ribose] polymerase 1(PARP1)-dependent and apoptosis-inducing factor (AIF)-mediated cell death, plays a crucial role in various disorders. In the present study, we aimed to investigate whether parthanatos is involved in the pathogenesis of DOR. We recruited 40 patients (20 DOR patients and 20 normal ovarian reserve (NOR) patients) and examined PAR expression and AIF translocation in their isolated cumulus GCs (granulosa cells) by fluorescence microscopy. Our results demonstrated that PAR expression and AIF nuclear translocation were significantly higher in cumulus GCs of DOR patients, suggesting that PARP1-dependent cell death may be associated with DOR pathophysiology. Moreover, we tested the protective function of melatonin on hydrogen peroxide (H2O2)-induced parthanatos in human ovarian cancer (IGROV1) cells. Our results demonstrated that H2O2 treatment of IGROV1 cells led to excessive protein PARylation and AIF translocation into the nuclei. Melatonin effectively inhibits PARylation, blocks translocation of AIF into the nucleus, and consequently decreases the risk of parthanatos in cumulus GCs.The methionine adenosyltransferase 2β gene (Mat2b) encodes for the regulatory subunit of methionine adenosyltransferase (MAT), which catalyzes the biosynthesis of S-adenosylmethionine. MAT2B interacts with G protein-coupled receptor kinase interacting ArfGAP1 to increase the activity of extracellular signal-regulated kinases (ERKs) for the regulation of cell growth, metabolism, and differentiation. ERK activity is also essential for oocyte meiosis in mice. However, the regulatory role of MAT2B in mouse oocyte meiosis remains unclear. Accordingly, this study investigated the effect of MAT2B on mouse oocyte maturation. Immunostaining showed that MAT2B localized predominantly in the nucleus of fully grown germinal vesicle (GV) oocytes. After germinal vesicle breakdown (GVBD), MAT2B homogeneously localized in the cytoplasm. A low oocyte maturation rate was observed in Mat2b siRNA-treated oocytes. Furthermore, Mat2b knockdown repressed the phosphorylation of ERK1/2 and consequently blocked MAPK. Denuded oocytes treated with 20 μM U0126 mainly blocked MAPK phosphorylation and affected oocyte maturation. The oocytes arrested at GVBD and metaphase I (MI) by Mat2b silencing or U0126 treatment had several types of abnormal microtubule assembly. Furthermore, Mat2b knockdown or U0126 treatment resulted in the aberrant expression of six maternal transcripts, namely, Fgf8, Cdc2, Gdf9, Padi6, Polr2d, and Tecb2. To the best of our knowledge, this study is the first to demonstrate that Mat2bs play an important role in mouse oocyte maturation though MAPK signaling.Lipid metabolism-associated molecule abhydrolase domain containing 5 (ABHD5) has been reported to have a role in insulin-mediated glucose uptake, the deregulation of it is associated with gestational diabetes mellitus (GDM). However, whether ABHD5 participates in glucose metabolism disorders in GDM patients has remained elusive.  https://www.selleckchem.com/products/GW501516.html  The present study aimed to clarify the role of ABHD5 in regulating insulin signaling in placentae during GDM. Reverse transcription-quantitative polymerase chain reaction (qRT-PCR) analysis was used for detecting the levels of ABHD5 and AMP kinase (AMPK), the insulin signaling molecules insulin receptor (INSR), INSR substrate (IRS1, IRS2), phosphoinositide 3-kinase (PI3K) and AKT, as well as the glucose transporter type 4 (GLUT-4) in placentae and the trophoblast cell line HTR-8/SVneo, while the protein level of ABHD5 was determined by western blotting. Pearson correlation analysis was performed to assess the correlation between the levels of ABHD5 and AMPK in placentae. In addition, ABHD5 overexpression in HTR-8/SVneo cells was achieved using plasmid vectors. The results indicated that the expression of ABHD5 and AMPK was dampened in placental tissues of females with GDM, and the levels of ABHD5 were positively correlated with AMPK. High-glucose (HG) treatment suppressed the expression of ABHD5, AMPK, GLUT-4, INSR, IRS, PI3K, and AKT in HTR-8/SVneo cells, and the overexpression of ABHD5 caused an elevation of the expression of these genes under normal and HG conditions in vitro. In conclusion, HG conditions induce insulin resistance of HTR-8/SVneo cells through downregulating ABHD5, which may account for impaired insulin signaling of placental tissues in GDM women.The objective of this study was to evaluate whether the renin-angiotensin system (RAS) is associated with maternal cardioprotective phenotype observed in post-lactated mice later in life. Following the delivery, CD-1 female mice were randomized to one of the following groups lactated (nursed pups for 3 weeks, n = 10) or non-lactated (pups were removed after birth, n = 10). The mice were sacrificed 6 months after the delivery, and tissues were collected. Protein levels of angiotensinogen, angiotensin type 1 and 2 receptors (AT1R, AT2R), angiotensin converting enzymes (ACE, ACE2), and MAS receptor were determined using Western blot. Results were analyzed using Student's t-test and Mann-Whitney test as appropriate (significance P less then 0.05). Angiotensinogen levels were significantly lower in the liver (P = 0.0002), and ACE was significantly decreased in the lungs (P = 0.04) and kidney (P = 0.001) from lactated mice as compared to non-lactated. The levels of AT2R in the kidney (P = 0.02) and visceral adipose tissue (VAT, P = 0.04), the ACE 2 in the VAT (P = 0.03) and heart (P = 0.04), and MAS receptor in VAT (P = 0.02) were significantly elevated in tissues from lactated mice. No other differences were found. Lactation led to the upregulation and downregulation of selected RAS components in lactated mice as compared to non-lactated group and may be a contributing factor to maternal cardioprotective phenotype later in life. Further studies are needed to dissect the mechanisms between lactation and the long-term maternal cardiometabolic benefits, which could lead to the therapies to prevent cardiovascular disease in women.