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Maternal undernutrition decreases sperm production in male offspring, possibly through insulin-like growth factor (IGF-I). To test this hypothesis, we fed pregnant Wistar rats ad libitum with a standard diet (CONTROL) or fed 50% of CONTROL intake, either throughout pregnancy (UNP), lactation (UNL, or both (UNPL). After weaning, male offspring (n = 10 per treatment) were fed a standard diet until postnatal day 160, when testes process for histological and molecular analyses. IGF-I immunostaining area and intensity in the testis were greater (P = 0.003) in the UNPL group compared to CONTROL, but lower in the UNP group (P < 0.0001). Levels of IGF-I receptor transcript were lower in the UNPL and UNL groups, compared to CONTROL. There were more Ki-67-positive germ and Sertoli cells, in all underfed groups than in CONTROL. Compared to CONTROL, frequency of spermatogenic cycle stage VII was lower in all underfed groups, and seminiferous tubule diameter was smaller in UNP and UNPL. Plasma FSH concentrations were greater in UNP male offspring compared to all groups (P = 0.05), whereas inhibin B concentrations were greater in UNP (P = 0.01) and UNL (P = 0.003) than in CONTROL or UNPL. Thus, prenatal undernutrition leads to a decrease in testicular IGF-I levels, whereas of pre- and postnatal undernutrition increased testicular IGF-I levels and decreased amounts of IGF-I receptor mRNA in adult offspring. We conclude that maternal undernutrition during pregnancy and lactation leads to long-lasting effects on adult male offspring testicular morphology, spermatogenesis, and IGF-I testicular system.

Objective:Maternal obesity is associated with obesity and metabolic disorders in offspring. However, there remains a paucity of data on strategies to reverse the effects of maternal obesity on maternal and offspring health. With maternal undernutrition, taurine supplementation improves outcomes in offspring mediated in part via improved glucose–insulin homeostasis. The efficacy of taurine supplementation in the setting of maternal obesity on health and well-being of offspring is unknown. We examined the effects of taurine supplementation on outcomes related to growth and metabolism in offspring in a rat model of maternal obesity.Design:Wistar rats were randomised to: 1) control diet during pregnancy and lactation (CON); 2) CON with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (MO); or 4) MO with taurine (MOT). Offspring were weaned onto the control diet for the remainder of the study.Results:At day 150, offspring body weights and adipose tissue weights were increased in MO groups compared to CON. Adipose tissue weights were reduced in MOT versus MO males but not females. Plasma fasting leptin and insulin were increased in MO offspring groups but were not altered by maternal taurine supplementation. Plasma homocysteine concentrations were reduced in all maternal taurine-supplemented offspring groups. There were significant interactions across maternal diet, taurine supplementation and sex for response to an oral glucose tolerance test , a high-fat dietary preference test and pubertal onset in offspring.Conclusions:These results demonstrate that maternal taurine supplementation can partially ameliorate adverse developmental programming effects in offspring in a sex-specific manner.

Prenatal glucocorticoids, commonly used in women at risk of preterm delivery, can predispose the newborn to disease in later life. Since male reproductive function is likely to reflect testis development during fetal life, we studied the effects of prenatal glucocorticoids on two key intra-testicular factors that play roles in cellular proliferation and differentiation, 3β-hydroxysteroid dehydrogenase (3β-HSD) and inhibin-α. Pregnant sheep (n=42) were treated with betamethasone (0.5 mg/kg) or saline (control) at 104, 111 and 118 days of gestation (DG). Testicular tissue was sampled from fetuses at 121 and 132DG, and from lambs at 45 and 90 postnatal days (PD). Within the betamethasone treated group, 3β-HSD immunostaining area was greater at 121DG than at 90PD (P=0.04), but the intensity of immunostaining was higher at 90PD than at 121DG (P=0.04), 132DG (P=0.04) and 45PD (P=0.03). Control animals showed no changes in 3β-HSD area or intensity of immunostaining. No significant differences were observed between treated and control animals in immunostaining area, but immunostaining was more intense in the treated group than in the control group at 90PD (P=0.03). For inhibin-α, the proportion of immunostaining area declined in treated offspring from 121DG to 45PD, in contrast to control values, but recovered fully by 90PD, concomitantly with the onset of spermatogenesis. In conclusion, prenatal betamethasone increased the postnatal testicular expression of inhibin-α but reduced the expression of 3β-HSD. These effects could compromise androgen-mediated testicular development and therefore adult capacity for spermatogenesis.

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40–42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

A life-course approach to reduction of risk of non-communicable diseases (NCD) suggests that early-life interventions may be more effective than lifestyle modifications in middle age. Knowledge translation to develop understanding of the Developmental Origins of Health and Disease (DOHaD) within the community offers the potential to encourage informed diet and lifestyle choices supporting reduction of NCD risk in current and future generations. Many women do not make sustained dietary change before or during pregnancy, therefore appropriate nutritional behaviours need to be established prior to adulthood. This makes adolescence an appropriate stage for interventions to establish suitable dietary and lifestyle behaviours. Therefore, we engaged adolescents in a school-based educational intervention, and assessed the value of this in development of understanding of DOHaD concepts to support behaviour change that could lead to NCD risk reduction in the next generation. Modules of course work were written for 11–14 year olds and trialled in nine schools. Matched pre- and post-intervention questionnaire responses from 238 students and 99 parents, and post-intervention interviews evaluated the intervention. Understanding of a link between maternal diet during pregnancy and the health of the foetus in adulthood increased from 46% to 76% following intervention. Post-intervention evidence suggests the programme facilitated discussion of diet, lifestyle and DOHaD concepts in most families. The intervention was effective in improving understanding of DOHaD concepts and in some cases led to appropriate behaviour change. However, the sustainability of these changes remains to be determined through on-going evaluation of attitudes and behaviour within this cohort.

It is well established that altered maternal nutrition may induce long-term metabolic consequences in offspring. However, the effects of maternal undernutrition during different developmental windows on sex-specific growth and metabolism in offspring are not well defined. We investigated the effect of moderate maternal undernutrition during pregnancy and/or lactation on postnatal growth and metabolic outcomes in offspring. Wistar rats were randomly assigned to one of four groups: (1) control (CONT) dams fed a standard diet throughout pregnancy and lactation; (2) dams undernourished to 50 % of CONT during pregnancy (UNP); (3) dams fed at 50 % of CONT throughout lactation (UNL); (4) dams fed at 50 % of CONT throughout pregnancy and lactation (UNPL). UNP and UNPL offspring were lighter at birth compared to CONT and UNL. UNL and UNPL offspring were growth restricted at weaning and remained smaller into adulthood. UNP males and females developed increased adiposity and hyperleptinaemia in adulthood compared to all other groups. Adiposity in UNL and UNPL males was similar to CONT offspring. In UNL and UNPL females, adiposity was lower than for CONT females. Markers of bone mass, lipid metabolism and hepatic function were altered in UNP offspring but were similar in UNL and UNPL offspring compared to CONT. Lack of catch-up growth during lactation in offspring of undernourished mothers prevented development of adiposity and related metabolic disorders in later life. These data highlight that the timing and duration of undernutrition during critical windows of development exert differential effects on postnatal outcomes in a sex-specific manner.

Maternal obesity during pregnancy is often characterized by fetal macrosomia but it can also result in fetal growth restriction in a subset of pregnancies. We hypothesized that mechanisms of this growth restriction may include adverse effects of maternal high fat (HF) intake on placental growth and function. Female rats (100 days old) were time-mated and randomly assigned to either a control (Con) or HF diet ad libitum throughout gestation. At E21, dams were killed; litter size and fetal and placental weights were recorded and maternal and fetal samples collected for further analyses. The HF diet resulted in a 54% increase in maternal body weight gain during gestation. In contrast, male and female fetal weights were reduced in HF pregnancies (P < 0.05), as were the weights of the junctional zone of the placenta (P = 0.013), whereas labyrinth zone weights were unaffected. The HF diet increased maternal and fetal plasma leptin levels (P < 0.05), but maternal and fetal insulin and fetal glucose levels were unaffected. Labyrinthine expression of PPARγ and total VEGFa mRNA, both markers of placental vascular development, were unaffected by consumption of the HF diet in placentas of male and female fetuses. Furthermore, maternal HF nutrition did not alter phosphorylated protein levels of either mammalian target of rapamycin or its downstream signaling factor eIF4E binding protein 1 (4E-BP1). These data show that in the rat, maternal HF nutrition results in fetal and placental junctional zone growth restriction, maternal and fetal hyperleptinemia but did not alter gene expression of markers of placental vascular development.

We previously reported that a maternal high fat (HF) diet resulted in adult offspring with increased adiposity and hyperleptinemia. As leptin has an inhibitory effect on adrenal steroidogenesis and a stimulatory effect on epinephrine synthesis, we hypothesized that key adrenal steroidogenic and catecholaminergic enzymes would be altered in these offspring. Wistar rats were randomized into three groups at weaning: (1) control dams fed a standard control chow diet from weaning and throughout pregnancy and lactation (CON), (2) dams fed a HF diet from weaning and throughout pregnancy and lactation (MHF) and (3) dams fed standard control chow diet throughout life until conception, then fed a HF diet in pregnancy and lactation (PLHF). Dams were mated at day 100 (P100). After birth at P22 (weaning), male offspring were fed a standard control chow (con) or high fat (hf) diet. At P160, plasma samples and adrenal tissues were collected. Postweaning hf diet significantly elevated plasma corticosterone concentrations in PLHF-hf offspring compared to PLHF-con. MHF nutrition increased adrenal adrenocorticotrophic hormone receptor (ACTH-R) mRNA levels compared to CON-con. 3β-hydroxysteroid dehydrogenase (3βHSD) mRNA levels were decreased in MHF compared to PLHF offspring. PhenylethanolamineN-methyltransferase (PNMT) mRNA levels were increased in MHF-hf offspring compared to MHF-con. Plasma homocysteine (HCY) concentrations were significantly elevated in CON-hf and MHF-hf offspring compared to chow-fed offspring, associated with elevated intakes of methionine and reduced intakes of pyridoxine. Immunoreactive leptin receptor (ObRb) and PNMT were colocalized in medullary chromaffin cells. This study suggests that a postweaning HF diet in offspring induced changes in adrenal gene expression levels that are dependent upon the level of maternal nutrition.