Placental insufficiency and its consequences

Gagnon, Robert

doi:10.1016/s0301-2115(03)00179-9

Cited by 260 publications

(203 citation statements)

References 70 publications

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“…1.2-fold increase in total uterine blood flow was found in ewes carrying twin conceptuses compared with a singleton conceptus at 120 to 140 days of gestation (Caton et al, 1979). Experimental reduction of uterine blood flow in ewes has been achieved by arterial occlusion and by the induction of embolisms using microspheres (Gagnon, 2003). Daily injection of microspheres for 21 days into the foetal abdominal aorta during the last trimester of pregnancy decreased foetal arterial oxygen content, which was followed by a 28% reduction in foetal weight (Murotsuki et al, 1996).…”

Section: Cardiovascular and Uterine Blood Flowmentioning

confidence: 99%

Litter-size-dependent intrauterine growth restriction in sheep

Gootwine

Spencer

Bazer

2007

Animal

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Regulation of foetal development in sheep depends on interactions between the intrinsic capacity of the foetus for growth and the maternal environment. Lambs born in multi-foetus litters have relatively small placentae with fewer cotelydons, and lower birth weights. Litter-size-dependent intrauterine growth restriction (IUGR) is evident at mid gestation when metabolic needs of the conceptus are moderate, and overnutrition of ewes with multiple foetuses does not promote growth of their foetuses to the size of singletons. Those observations suggest that placental and conceptus growth in multi-foetus pregnancies is reprogrammed at mid gestation by an as yet undefined mechanism to attenuate foetal growth. This may protect the foetus from severe nutritional insult during late gestation, when its daily growth rate is at a maximum. In that way, lambs born in large litters with relatively lower birth weights may not experience the long-term physiological insults that can be observed in small lambs born to undernourished ewes.

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Section: Cardiovascular and Uterine Blood Flowmentioning

confidence: 99%

Litter-size-dependent intrauterine growth restriction in sheep

Gootwine

Spencer

Bazer

2007

Animal

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“…A proportion of FGR cases can be attributed to obvious maternal (e.g., hypertensive disorders, pre-gestational diabetes and malnutrition), fetal (e.g., genetic defects) or placental (e.g., infarcts) causes, but the aetiology remains uncertain in up to 70% of cases and hence these are termed 'idiopathic FGR'. Idiopathic FGR is frequently associated with abnormal placental development and/or function, and as a consequence, with suboptimal delivery of oxygen and nutrients to the fetus (Gagnon 2003). Furthermore, there is increasing evidence that perturbations in placental development related to abnormal trophoblast function may lead to the compromised pregnancy outcomes characteristic of FGR (Bernstein & Divon 1997).…”

Section: Introductionmentioning

confidence: 99%

Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction

Borg¹,

Yong²,

Lappas³

et al. 2015

Reproduction

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Abnormal trophoblast function is associated with fetal growth restriction (FGR). The JAK-STAT pathway is one of the principal signalling mechanisms by which cytokines and growth factors modulate cell proliferation, differentiation, cell migration and apoptosis. The expression of placental JAK-STAT genes in human idiopathic FGR is unknown. In this study, we propose the hypothesis that JAK-STAT pathway genes are differentially expressed in idiopathic FGR-affected pregnancies and contribute to abnormal feto-placental growth by modulating the expression of the amino acid transporter SNAT2, differentiation marker CGB/human chorionic gonadotrophin betasubunit (b-hCG) and apoptosis markers caspases 3 and 8, and TP53. Expression profiling of FGR-affected placentae revealed that mRNA levels of STAT3, STAT2 and STAT5B decreased by 69, 52 and 50%, respectively, compared with gestational-age-matched controls. Further validation by real-time PCR and immunoblotting confirmed significantly lower STAT3 mRNA and STAT3 protein (total and phosphorylated) levels in FGR placentae. STAT3 protein was localised to the syncytiotrophoblast (ST) in both FGR and control placentae. ST differentiation was modelled by in vitro differentiation of primary villous trophoblast cells from first-trimester and term placentae, and by treating choriocarcinoma-derived BeWo cells with forskolin in cell culture. Differentiation in these models was associated with increased STAT3 mRNA and protein levels. In BeWo cells treated with siRNA targeting STAT3, the mRNA and protein levels of CGB/b-hCG, caspases 3 and 8, and TP53 were significantly increased, while that of SNAT2 was significantly decreased compared with the negative control siRNA. In conclusion, we report that decreased STAT3 expression in placentae may contribute to abnormal trophoblast function in idiopathic FGR-affected pregnancies.

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“…Obvious maternal, fetal and placental causes of FGR account only for one third of FGR cases (3), while the remaining two thirds are termed idiopathic. Idiopathic FGR is often associated with placental insufficiency (4) where the placentae are often smaller and show numerous morphological defects such as reduced trophoblast proliferation and abnormal villous vasculature with less branched terminal villi (5).…”

Section: Introductionmentioning

confidence: 99%