The maternal endocrine environment in the low-protein model of intra-uterine growth restriction

Fernandez‐Twinn, Denise S.; Ozanne, Susan E.; Ekizoglou, S.; Doherty, C.; James, L A; Gusterson, Barry A.; Hales, C. N.

doi:10.1079/bjn2003967

Cited by 136 publications

(126 citation statements)

References 34 publications

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“…Pdx-1 expression is repressed by glucocorticoids during pancreatic organogenesis (Shen et al 2003). However, while corticosterone levels are elevated in rat fetuses following maternal calorie reduction (Lesage et al 2001), maternal and fetal plasma corticosterone levels were not changed following LP diet (Fernandez-Twinn et al 2003). Administration of LP diet for week 2 of pregnancy only had a greater impact on islet size, and the number of b cells, than did LP for both weeks 1 and 2, or week 3 alone, within female offspring.…”

Section: Discussionmentioning

confidence: 86%

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

Chamson-Reig¹,

Thyssen²,

Arany³

et al. 2006

Journal of Endocrinology

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Restriction of dietary protein during gestation and lactation in the rat results in a reduction in b cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1-2)), the second week only (LP (2)), or the third week (LP (3)). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 mm 2 ) and medium (between 5000 and 10 000 mm 2 ) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of b cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in midgestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both b cell development and insulin gene transcription, was decreased in female offspring following LP (1-2) and LP (3), but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of b cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of b cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.

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Section: Discussionmentioning

confidence: 86%

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

Chamson-Reig¹,

Thyssen²,

Arany³

et al. 2006

Journal of Endocrinology

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“…Female rats fed a diet enriched with n-3 polyunsaturated fatty acids had a 48% increase in serum concentrations of 17b-estradiol compared with rats fed a diet enriched with n-6 fatty acids (Hilakivi-Clarke et al 2002). Similarly, female rats fed a low protein diet had a significant increase in 17b-estradiol compared with those fed a control diet (Fernandez-Twinn et al 2003). Nutritionally restricted heifers have decreased serum estrogen concentrations at day 200 of pregnancy compared with larger, non-food restricted heifers (Killen et al 1989).…”

Section: Introductionmentioning

confidence: 92%

Maternal diet composition alters serum steroid and free fatty acid concentrations and vaginal pH in mice

Whyte¹,

Alexenko²,

Davis³

et al. 2007

Journal of Endocrinology

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We examined the effects of three maternal diets (very high fat (VHF), low fat (LF), and control (Purina 5015)) on serum steroids, free fatty acids (FFA), and vaginal pH in National Institutes of Health Swiss mice. Females were fed (VHF, nZ33; LF, nZ33; 5015, nZ48) from 4 to 16 weeks of age. Following breeding, female serum was collected at 0 . 5 (pre-implantation, early diestrus) or 8 . 5 (post-implantation, mid-diestrus) days post-coitus (dpc). The serum concentrations of 17b-estradiol, testosterone, progesterone, and FFA were analyzed at both collection points, and vaginal pH at 0 . 5 dpc. Striking differences in steroids and FFA were observed at 0 . 5 dpc among the groups. Estradiol was higher in the VHF (14 . 1G3 . 0 pg/ml), compared with LF mice (5 . 2G2 . 3 pg/ml; P%0 . 05). In contrast, 0 . 5 dpc testosterone was lower in the VHF (10 . 5G3 . 0 pg/ml) versus the LF group (32 . 7G8 . 4 pg/ml; P%0 . 05). At 8 . 5 dpc, progesterone was higher in the VHF (89 . 6G6 . 7 ng/ml) versus the 5015 group (60 . 1G4 . 9 ng/ml; P%0 . 05). VHF mice had higher FFA concentrations at 0 . 5 dpc (1 . 0G0 . 2 mmol/l) than LF and control mice (0 . 5G0 . 1 and 0 . 6G0 . 1 mmol/l respectively; P%0 . 05). At 8 . 5 dpc, VHF females had higher serum FFA (0 . 8G0 . 1 mmol/l) than LF and control females (0 . 4G0 . 1 and 0 . 6G0 . 1 mmol/l; P%0 . 05). Mean vaginal pH of VHF females (6 . 41G0 . 09) was lower than 5015 females (6 . 76G 0 . 10; P%0 . 05). These diet-induced alterations in serum steroid and FFA concentrations might affect several reproductive processes, including preferential fertilization by one class of sperm over the other and sex bias in pre-and post-implantational embryonic development.

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“…Foetal growth retardation and its consequences in case of maternal protein restriction may occur however without overexposure to glucocorticoids. 53 One mechanism supposed to participate to the high level of foetal glucocorticoids is the downregulation of 11b-hydroxysteroid dehydrogenase gene expression, an enzyme that inactivates the maternal physiological glucocorticoids during their passage across the placenta. 51 Programming of the HPA axis has been linked to permanent changes in hippocampal corticosteroid receptor populations, reducing glucocorticoid feedback in this area.…”

Section: Animal Models For Programming Of Obesitymentioning

confidence: 99%

Programming of obesity and cardiovascular disease

2004

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BACKGROUND: There is evidence that malnutrition in early life induces a growth retardation leading, in adult life, to manifest components of the metabolic syndrome. However, the impact on obesity seems less clearly established. OBJECTIVE: To review the effects of foetal and postnatal malnutrition on the programming of obesity in the context of the metabolic syndrome, as well as the link between central obesity and cardiovascular diseases. METHODS: Included in the review were recent papers exploring the mechanisms linking maternal nutrition with impaired foetal growth and later obesity, cardiovascular disease, hypertension and diabetes in humans and animals. RESULTS: The programming of obesity during foetal and early postnatal life depends of the timing of maternal malnutrition as well as the postnatal environment. Obesity arises principally in offspring submitted to malnutrition during early stages of gestation and which presented early catch-up growth. The programming may involve the dysregulation of appetite control or the hormonal environment leading to a context favourable to obesity development (hypersecretion of corticosteroids, hyperinsulinaemia and hyperleptinaemia and anomalies in the IGF axis). Adipose tissue secretes actively several factors implicated in inflammation, blood pressure, coagulation and fibrinolysis. The programmed development of intra-abdominal obesity after early growth restriction may thus favour higher prevalence of hypertension and cardiovascular diseases. CONCLUSIONS: Abdominal obesity appears in malnourished offspring and is aggravated by early catch-up growth. Higher rates of intra-abdominal obesity observed after growth restriction may participate to hypertension and create atherothrombotic conditions leading to the development of cardiovascular diseases.

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The maternal endocrine environment in the low-protein model of intra-uterine growth restriction

Cited by 136 publications

References 34 publications

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific

Maternal diet composition alters serum steroid and free fatty acid concentrations and vaginal pH in mice

Programming of obesity and cardiovascular disease

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