Yazar "Jiang, Honghua" seçeneğine göre listele

Listeleniyor 1 - 3 / 3
  • Küçük Resim Yok
    Öğe
    Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes
    (Pergamon-Elsevier Science Ltd, 2023) Zhang, Hao; Zheng, Yi; Liu, Xiaoyun; Zha, Xia; Elsabagh, Mabrouk; Ma, Yi; Jiang, Honghua
    Bisphenol A (BPA)-induced oxidative stress (OS) and its potentially associated autophagy and apoptosis have not been studied previously in pregnant ewes. Accordingly, this study investigated the underlying mechanisms of BPA-induced autophagy and apoptosis in the placenta and primary trophoblasts of pregnant ewes exposed to BPA both in vivo and in vitro. In vivo experiment, pregnant Hu ewes (n = 8) were exposed to 5 mg/kg/d of BPA compared to control ewes (n = 8) receiving only corn oil from day 40 through day 110 of gestation. Exposure to BPA during gestation resulted in placental insufficiency, fetal growth restriction (FGR), autophagy, endoplasmic reticulum stress (ERS), mitochondrial dysfunction, OS, and apoptosis in type A placentomes. Regarding in vitro model, primary ovine trophoblasts were exposed to BPA, BPA plus chloroquine (CQ; an autophagy inhibitor) or BPA plus rapamycin (RAP; an autophagy activator) for 12 h. Data illustrated that exposure to BPA enhanced autophagy (ULK1, Beclin-1, LC3, Parkin, and PINK1), ERS (GRP78, CHOP10, ATF4, and ATF6) and apoptosis (Caspase 3, Bcl-2, Bax, P53) but decreased the antioxidant (CAT, Nrf2, HO-1, and NQO1)-related mRNA and protein expressions as well as impaired the mitochondrial function. Moreover, treatment with CQ exacerbated the BPA-mediated OS, mitochondrial dysfunction, apoptosis, and ERS. On the contrary, RAP treatment coun-teracted the BPA-induced trophoblast dysfunctions mentioned above. Overall, the findings illustrated that BPA exposure could contribute to autophagy in the ovine placenta and trophoblasts and that autophagy, in turn, could alleviate BPA-induced apoptosis, mitochondrial dysfunction, ERS, and OS. These results offer new mechanistic insights into the role of autophagy in mitigating BPA-induced placental dysfunctions and FGR.
  • Küçük Resim Yok
    Öğe
    Dietary Supplementation of L-Arginine and N-Carbamylglutamate Attenuated the Hepatic Inflammatory Response and Apoptosis in Suckling Lambs with Intrauterine Growth Retardation
    (Hindawi Ltd, 2020) Zhang, Hao; Fan, Yaotian; Elsabagh, Mabrouk; Guo, Shuang; Wang, Mengzhi; Jiang, Honghua
    L-arginine (Arg) is a semiessential amino acid with several physiological functions. N-Carbamylglutamate (NCG) can promote the synthesis of endogenous Arg in mammals. However, the roles of Arg or NCG on hepatic inflammation and apoptosis in suckling lambs suffering from intrauterine growth restriction (IUGR) are still unclear. The current work is aimed at examining the effects of dietary Arg and NCG on inflammatory and hepatocyte apoptosis in IUGR suckling lambs. On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 432 twin lambs. Normal-birthweight and IUGR Hu lambs were allocated randomly (n=12/group) to control (CON), IUGR, IUGR+1% Arg, or IUGR+0.1% NCG groups. Lambs were fed for 21 days from 7 to 28 days old. Compared with CON lambs, relative protein 53 (P53), apoptosis antigen 1 (Fas), Bcl-2-associated X protein (Bax), caspase-3, cytochrome C, tumor necrosis factor alpha (TNF-alpha), nuclear factor kappa-B (NF-kappa B) p65, and NF-kappa B pp65 protein levels were higher (P<0.05) in liver from IUGR lambs, whereas those in liver from IUGR lambs under Arg or NCG treatment were lower than those in IUGR lambs. These findings indicated that supplementing Arg or NCG reduced the contents of proinflammatory cytokines at the same time when the apoptosis-related pathway was being suppressed, thus suppressing the IUGR-induced apoptosis of hepatic cells.
  • Küçük Resim Yok
    Öğe
    Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model
    (Bmc, 2023) Zhang, Hao; Zha, Xia; Zheng, Yi; Liu, Xiaoyun; Elsabagh, Mabrouk; Wang, Hongrong; Jiang, Honghua
    Background Exposure to bisphenol A (BPA), an environmental pollutant known for its endocrine-disrupting properties, during gestation has been reported to increase the risk of fetal growth restriction (FGR) in an ovine model of pregnancy. We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta, oxidative stress, inflammatory responses, autophagy and endoplasmic reticulum stress (ERS). However, precise mechanisms underlying the BPA-induced placental dysfunction, and subsequently, FGR, as well as the potential involvement of placental ERS in these complications, remain to be investigated. Methods In vivo experiment, 16 twin-pregnant (from d 40 to 130 of gestation) Hu ewes were randomly distributed into two groups (8 ewes each). One group served as a control and received corn oil once a day, whereas the other group received BPA (5 mg/kg/d as a subcutaneous injection). In vitro study, ovine trophoblast cells (OTCs) were exposed to 4 treatments, 6 replicates each. The OTCs were treated with 400 mu mol/L BPA, 400 mu mol/L BPA + 0.5 mu g/mL tunicamycin ( Tm; ERS activator), 400 mu mol/L BPA + 1 mu mol/L 4-phenyl butyric acid (4-PBA; ERS antagonist) and DMEM/ F12 complete medium (control), for 24 h. Results In vivo experiments, pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency, progesterone (P4) level and fetal weight, and an increase in placental estrogen (E2) level, together with barrier dysfunctions, OS, inflammatory responses, autophagy and ERS in type A cotyledons. In vitro experiment, the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy, ERS, pro-apoptosis and inflammatory response, and a decrease in the P4 level and the related protein and gene expressions of antioxidant, anti-apoptosis and barrier function. Moreover, treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine (the increased E2 level and decreased P4 level), OS, inflammatory responses, autophagy, and ERS. However, treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above. Conclusions In general, the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs, and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine, OS, inflammatory responses, and autophagy. These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.