Sexual Dimorphism of the Feto-Placental Phenotype in Response to a High Fat and Control Maternal Diets in a Rabbit Model

Abstract

Maternal environment during early developmental stages plays a seminal role in the establishment of adult phenotype. Using a rabbit model, we previously showed that feeding dams with a diet supplemented with 8% fat and 0.2% cholesterol (HH diet) from the prepubertal period and throughout gestation induced metabolic syndrome in adult offspring. Here, we examined the effects of the HH diet on feto-placental phenotype at 28 days post-coïtum (term = 31days) in relation to earlier effects in the blastocyst (Day 6). At 28 days, both male and female HH fetuses were intrauterine growth retarded and dyslipidemic, with males more affected than females. Lipid droplets accumulated in the HH placentas’ trophoblast, consistent with the increased concentrations in cholesteryl esters (3.2-fold), triacylglycerol (2.5-fold) and stored FA (2.12-fold). Stored FA concentrations were significantly higher in female compared to male HH placentas (2.18-fold, p<0.01), whereas triacylglycerol was increased only in HH males. Trophoblastic lipid droplet accumulation was also observed at the blastocyst stage. The expression of numerous genes involved in lipid pathways differed significantly according to diet both in term placenta and at the blastocyst stage. Among them, the expression of LXR-α in HH placentas was reduced in HH males but not females. These data demonstrate that maternal HH diet affects the blastocyst and induces sex-dependent metabolic adaptations in the placenta, which appears to protect female fetuses from developing severe dyslipidemia.

Placental contribution to nutritional programming of health and diseases: epigenetics and sexual dimorphism

“…In this last study, the diet affected placental weight and placental efficiency regardless of the sex of the fetuses. In rabbits, a highfat diet before and throughout gestation induced high adiposity in the mothers, while their fetuses were of smaller weight, whereas placental efficiency remained unchanged (Tarrade et al, 2013). All these data demonstrate that variable results on fetal and placental weight have been reported, including a decrease or increase of weight or no effect, depending on species, diet composition and the time window of diet application.…”

“…In contrast, fetuses displayed a dyslipidaemia that affected more males than females. Therefore, there was a physiological adaptation, with a relative protection of the female fetuses from developing dyslipidaemia (Tarrade et al, 2013). Finally, a recent study showed that maternal obesity in the mouse induced a reduction in placenta labyrinth thickness and cell proliferation.…”

“…In a non-human primate model where obesity was induced by a chronic high-fat diet, placentas showed an increase of infarction and chorionic villous calcification (Frias et al, 2011). Using transmission electron microscopy, an abnormal accumulation of lipid droplets has been described in placentas from rabbits fed a high-fat diet (Tarrade et al, 2013). In contrast, in placentas from mouse mothers fed a high-fat diet, no changes in the structure of the labyrinth and the spongiotrophoblast, or in the number and size of cells in the two layers were observed (Gabory et al, 2012).…”

Early sex-dependent differences in response to environmental stress

“…In rats, high-fat and high-salt diets lowered placental size of males, increasing the expression of genes associated with metabolism and pro-inflammatory mediators, which has been related to future cardiometabolic disturbances (Reynolds et al 2015). In rabbits, high-fat and high-cholesterol diets provoke higher accumulation of triacylglycerol in males while they upregulate genes of the lipid pathway in females (Tarrade et al 2013). In non-human primates, nutritional restriction has been reported to suppress genes related to programmed cell death and enhance genes associated with cell proliferation in female placentae.…”

DOHaD et programmation pré- et péri-conceptionnelle

“…Une hyperthermie et une inflammation maternelle provoquée par une injection de lipopolysaccharide (LPS) juste après la fécondation [26], une sous-nutrition protéique durant la période pré-et/ou péricon-ceptionnelle, par exemple, peuvent perturber le développement chez la descendance, avec des différences en fonction du sexe [27,28]. Chez le lapin, une alimentation maternelle enrichie en lipides est associée à des changements d'expression de gènes dans l'embryon et à une accumulation de gouttelettes lipidiques dans le trophoblaste du blastocyste, retrouvée, en fin de gestation, dans le placenta (d'origine trophoblastique) [29]. Récemment, la notion de transmission paternelle, non génétique, de pathologies à long terme a émergé [30].…”