Mayu Kurokawa1,2, Ai Takeshita2,3, Shu Hashimoto4, Masayasu Koyama1, Yoshiharu Morimoto5, Daisuke Tachibana1. 1. Women's Lifecare Medicine, Obstetrics and Gynecology, School of Medicine, Osaka City University, 545-8585, Osaka, Japan. 2. Graduate School of Medicine, Reproductive Science, Osaka City University, Osaka, 545-8585, Japan. 3. Department of Anatomy and Neurobiology, Faculty of Medicine, Kindai University, Osaka, 589-8511, Japan. 4. Graduate School of Medicine, Reproductive Science, Osaka City University, Osaka, 545-8585, Japan. hashimoto@ivfnamba.com. 5. HORAC Grand Front Osaka Clinic, Osaka, 530-0011, Japan.
Abstract
PURPOSE: The latest treatments do not sufficiently prevent miscarriage and fetal growth restriction (FGR) in pregnant women. Here, we assessed the effects of a human protein, CTRP6, that specifically inhibits the activation of the alternative complement pathway on miscarriage, fetal and placental development. METHODS: Pregnant CBA/J mice mated with DBA/2 male mice as a model of spontaneous abortion and FGR were randomly divided into the control and CTRP6 groups. In the CTRP6 group, the mice were intravenously administered CTRP6 on days 4.5 and 6.5 post-conception (dpc). The abortion rate and fetal and placental weights on 14.5 dpc were examined. Remodeling of the spiral artery was also assessed. RESULTS: The abortion rate in the CTRP6 group (13%) was reduced compared to the control group (21%), but there was no statistical difference. The placental and fetal weights in the CTRP6 group were also heavier than those in the control (P < 0.05). Moreover, the thickness of the blood vessel wall in the CTRP6 group was significantly thinner than that in the control (P < 0.05) and comparable to that in the non-abortion model (CBA/J x BALB). The ratio of the inner-per-the-outer diameter of the spiral artery increased more in the CTRP6 group than that in the control (P < 0.05). As well, the Th1/Th2 cytokine ratio was significantly reduced by CTRP6 treatment. CONCLUSIONS: Taken together, the supplementation with a protein that regulates the alternative complement pathway in vivo improves FGR and promotes spiral artery remodeling in a mouse model of miscarriage and FGR.
PURPOSE: The latest treatments do not sufficiently prevent miscarriage and fetal growth restriction (FGR) in pregnant women. Here, we assessed the effects of a human protein, CTRP6, that specifically inhibits the activation of the alternative complement pathway on miscarriage, fetal and placental development. METHODS: Pregnant CBA/J mice mated with DBA/2 male mice as a model of spontaneous abortion and FGR were randomly divided into the control and CTRP6 groups. In the CTRP6 group, the mice were intravenously administered CTRP6 on days 4.5 and 6.5 post-conception (dpc). The abortion rate and fetal and placental weights on 14.5 dpc were examined. Remodeling of the spiral artery was also assessed. RESULTS: The abortion rate in the CTRP6 group (13%) was reduced compared to the control group (21%), but there was no statistical difference. The placental and fetal weights in the CTRP6 group were also heavier than those in the control (P < 0.05). Moreover, the thickness of the blood vessel wall in the CTRP6 group was significantly thinner than that in the control (P < 0.05) and comparable to that in the non-abortion model (CBA/J x BALB). The ratio of the inner-per-the-outer diameter of the spiral artery increased more in the CTRP6 group than that in the control (P < 0.05). As well, the Th1/Th2 cytokine ratio was significantly reduced by CTRP6 treatment. CONCLUSIONS: Taken together, the supplementation with a protein that regulates the alternative complement pathway in vivo improves FGR and promotes spiral artery remodeling in a mouse model of miscarriage and FGR.
Authors: Santiago Munné; Brian Kaplan; John L Frattarelli; Tim Child; Gary Nakhuda; F Nicholas Shamma; Kaylen Silverberg; Tasha Kalista; Alan H Handyside; Mandy Katz-Jaffe; Dagan Wells; Tony Gordon; Sharyn Stock-Myer; Susan Willman Journal: Fertil Steril Date: 2019-09-21 Impact factor: 7.329
Authors: D H Munn; M Zhou; J T Attwood; I Bondarev; S J Conway; B Marshall; C Brown; A L Mellor Journal: Science Date: 1998-08-21 Impact factor: 47.728