Understanding the placental mechanisms underpinning increased fetal growth in a mouse model of FGR following sildenafil citrate treatment: Insight from network analyses

Placenta ◽  
2015 ◽  
Vol 36 (9) ◽  
pp. A9-A10
Author(s):  
Adam Stevens ◽  
Richard Unwin ◽  
Nitin Rustogi ◽  
Andrew Dowsey ◽  
Garth Cooper ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fetal Growth ◽  
Sildenafil Citrate ◽  
Network Analyses

scholarly journals Sildenafil Citrate Rescues Fetal Growth in the Catechol- O -Methyl Transferase Knockout Mouse Model

Hypertension ◽  
2012 ◽  
Vol 59 (5) ◽  
pp. 1021-1028 ◽  
Author(s):  
Joanna L. Stanley ◽  
Irene J. Andersson ◽  
Rajan Poudel ◽  
Christian F. Rueda-Clausen ◽  
Colin P. Sibley ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fetal Growth ◽  
Knockout Mouse ◽  
Sildenafil Citrate ◽  
Methyl Transferase ◽  
Knockout Mouse Model

Maternal administration of Sildenafil Citrate alters fetal vascular function in a mouse model of fetal growth restriction

Placenta ◽  
2013 ◽  
Vol 34 (9) ◽  
pp. A22
Author(s):  
Lewis Renshall ◽  
Elizabeth Cowley ◽  
Susan Greenwood ◽  
Mark Dilworth ◽  
Mark Wareing
Keyword(s):  
Mouse Model ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Vascular Function ◽  
Growth Restriction ◽  
Sildenafil Citrate ◽  
Maternal Administration

scholarly journals Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77748 ◽  
Author(s):  
Mark Robert Dilworth ◽  
Irene Andersson ◽  
Lewis James Renshall ◽  
Elizabeth Cowley ◽  
Philip Baker ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Fetal Weight ◽  
Sildenafil Citrate ◽  
Vascular Phenotype

scholarly journals Antenatal sildenafil citrate treatment increases offspring blood pressure in the placental-specific Igf2 knockout mouse model of FGR

2020 ◽  
Vol 318 (2) ◽  
pp. H252-H263 ◽  
Author(s):  
L. J. Renshall ◽  
E. C. Cottrell ◽  
E. Cowley ◽  
C. P. Sibley ◽  
P. N. Baker ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Weight Gain ◽  
Mouse Model ◽  
Systolic Blood Pressure ◽  
Fetal Growth ◽  
Knockout Mouse ◽  
Female Offspring ◽  
Sildenafil Citrate ◽  
Postnatal Weight Gain

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring ( P < 0.05) and reduced glucose sensitivity in both WT ( P < 0.01) and P0 ( P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life. NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.

scholarly journals The role of sildenafil citrate in the treatment of fetal growth restriction: a randomized controlled trial

2019 ◽  
Vol 8 (5) ◽  
pp. 1840
Author(s):  
Ahmed Abdelshafy ◽  
Khaled Ibrahim Abdullah ◽  
Sherif Ashoush ◽  
Heba E. Hosni
Keyword(s):  
Middle Cerebral Artery ◽  
Fetal Growth ◽  
Cerebral Artery ◽  
Fetal Growth Restriction ◽  
Umbilical Artery ◽  
Controlled Trial ◽  
Maternity Hospital ◽  
Growth Restriction ◽  
Sildenafil Citrate ◽  
Doppler Velocity

Background: This study was aimed to evaluate the effect of sildenafil citrate on Doppler velocity indices in patients with fetal growth restriction (FGR) associated with impaired placental circulation.Methods: A double-blinded, parallel group randomized clinical trial (clinicaltrials.gov NCT02590536) was conducted in Ain Shams Maternity Hospital, in the period between October 2015 and June 2017. Ninety pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were randomized to either sildenafil citrate 25 mg orally every 8 hours or placebo visually-identical placebo tablets with the same regimen. The primary outcome of the study was the change in umbilical artery and fetal middle cerebral artery indices.Results: There was a significant improvement in umbilical and middle cerebral artery indices after sildenafil administration p<0.001. Present study observed that, sildenafil group, in comparison to placebo, has a significantly higher mean neonatal birth weight. 1783±241g vs 1570±455g (p<0.001). There was a significantly higher mean gestational age at delivery in women in sildenafil group 35.3±1.67 weeks, whereas it was lower in the placebo group 33.5±1.7 weeks. The side effects as headache, palpitation and facial flushing were significantly higher in sildenafil group compared to placebo group.Conclusions: The use sildenafil citrate in pregnancies with fetal growth restriction (FGR) improved the feto-placental Doppler indices (pulsatility index of umbilical artery and middle cerebral artery) and improved neonatal outcomes.

Effects of vitrification and the superovulated environment on placental function and fetal growth in an IVF mouse model

2020 ◽  
Vol 26 (8) ◽  
pp. 624-635
Author(s):  
C Roeca ◽  
E Silva ◽  
C Barentsen ◽  
T L Powell ◽  
T Jansson
Keyword(s):  
Mouse Model ◽  
Fetal Growth ◽  
Gestational Age ◽  
Large For Gestational Age ◽  
Placental Development ◽  
Developmental Potential ◽  
Placental Function ◽  
Uterine Environment ◽  
Embryonic Viability ◽  
Human Ivf

Abstract In studies of human IVF, as compared to frozen embryo transfer (ET), fresh ET is associated with smaller infants and higher risk of small for gestational age infants. Recent observations suggest that ET using vitrified embryos is associated with higher pregnancy and live birth rates compared to fresh ET, but increased rates of large for gestational age infants. The mechanisms underlying these associations are largely unknown, and available evidence suggests that the influence of IVF, vitrification and the superovulated (SO) uterine environment on placental function and fetal growth is complex. This warrants further investigation given the prevalent practice in human IVF of both fresh ET into a SO uterine environment, and vitrification with ET into a more physiologic uterine environment. Using a mouse model that closely resembles human IVF, we investigated if vitrification of IVF embryos better preserves placental function and results in better pregnancy outcomes as compared to fresh ET because of transfer into a more physiologic endometrium. We found that the SO environment, independent of vitrification status, reduced implantation rates, inhibited placental mechanistic target of rapamycin signaling and induced placental stress signaling, resulting in fetal growth restriction (1.080 ± 0.05 g estrous fresh (n = 17 litters), 1.176 ± 0.05 g estrous vitrified (n = 12), 0.771 ± 0.06 g SO fresh (n = 15), 0.895 ± 0.08 g SO vitrified (n = 10), P &lt; 0.0001). In addition, our study suggests that vitrification impairs the developmental potential of IVF blastocysts that resulted in a significantly smaller litter size (2.6 ± 2.3 fresh estrous vs 2.5 ± 2.4 fresh SO vs 1.6 ± 1.7 estrous vitrified vs 1.7 ± 1.8 SO vitrified, P = 0.019), with no effect on fetal growth or placental function at term. Our findings suggest that vitrification may negatively impact early embryonic viability, while the SO maternal uterine environment impairs both placental development and fetal growth in IVF.

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