Maternal omega-3 fatty acid intake increases placental labyrinthine antioxidant capacity but does not protect against fetal growth restriction induced by placental ischaemia–reperfusion injury

Abstract

Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders. Oxidative stress occurs when excess reactive oxygen species (ROS) damages cellular components, an outcome limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) also limits ROS production. We recently reported that maternal dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation reduced placental oxidative damage and enhanced fetal and placental growth in the rats. Here, we examined the effect of n-3 PUFAs on placental antioxidant defences and whether n-3 PUFA supplementation could prevent growth restriction induced by placental ischaemia-reperfusion (IR), a known inducer of oxidative stress. Rats were fed either standard or high-n-3 PUFA diets from day 1 of pregnancy. Placentas were collected on days 17 and 22 in untreated pregnancies (termZday 23) and at day 22 following IR treatment on day 17. Expression of several antioxidant enzyme genes (Sod1, Sod2, Sod3, Cat, Txn1 and Gpx3) and Ucp2 was measured by quantitative RT-PCR in the placental labyrinth zone (LZ) and junctional zone (JZ). Cytosolic superoxide dismutase (SOD), mitochondrial SOD and catalase (CAT) activities were also analyzed. Maternal n-3 PUFA supplementation increased LZ mRNA expression of Cat at both gestational days (2-and 1.5-fold respectively; P!0.01) and female Sod2 at day 22 (1.4-fold, P!0.01). Cytosolic SOD activity increased with n-3 PUFA supplementation at day 22 (1.3-fold, P!0.05). Sod1 and Txn1 expression decreased marginally (30 and 22%, P!0.05). JZ antioxidant defences were largely unaffected by diet. Despite increased LZ antioxidant defences, maternal n-3 PUFA supplementation did not protect against placental IR-induced growth restriction of the fetus and placental LZ.

Maternal dietary omega-3 fatty acids and placental function

“…We recently demonstrated that maternal n-3 PUFA supplementation enhanced mRNA expression and activity of major antioxidant enzymes in the placental LZ across the final third of rat pregnancy (Jones et al 2013c), coincident with reduced placental oxidative damage (Jones et al 2013a). These findings are consistent with an in vitro study, in which treatment of placental BeWo cells with modest levels of DHA reduced oxidative DNA damage and increased cell survival when challenged by an oxidative insult (Shoji et al 2009).…”

“…Similarly, in human placental explants, DHA administration reduced LPS-induced oxidative damage and restored antioxidant capacity (Stark et al 2013). Dietary n-3 PUFAs may also reduce ROS generation, given that they increase Ucp2 mRNA expression in mouse white adipose tissue (Hun et al 1999) R148 M L Jones and others placental tissue, being predominantly expressed by the syncytiotrophoblast (Stark et al 2012), although maternal dietary n-3 PUFA supplementation in the rat did not affect placental Ucp2 mRNA expression in our recent study (Jones et al 2013c). The effect of maternal n-3 PUFA supplementation on oxidative status of the early gestation placenta, and of particular interest during the onset of placental perfusion, is unknown.…”

Sexual dimorphism in the effect of maternal obesity on antioxidant defense mechanisms in the human placenta

“…In murine models obesity alters placental morphology, cell proliferation and inflammation [44] and maternal diet alters placental gene expression [45] and epigenetic systems [46] in a sexually dimorphic manner. Maternal dietary n-3 polyunsaturated fatty acid administration gave sexually dimorphic changes in gene expression in placentas in mice [47] and in humans [41]. The underlying basis for these sexually dimorphic differences in gene expression in placenta remains unknown.…”

Omega‐3 supplementation during pregnancy to prevent recurrent intrauterine growth restriction: systematic review and meta‐analysis of randomized controlled trials

“…arachidonic acid), plays a major role in inflammation. Moreover, omega‐3 fatty acids increase placental labyrinthine antioxidant capacity. It has been hypothesized that omega‐3 increases fetal growth rate by improving placental blood flow due to a lowered thromboxane/prostacyclin ratio and blood viscosity by correcting the imbalance in vasoactive PG.…”