Accumulating evidence suggest that the concept of programming can also be applied to reproductive development and function, representing an ever expanding research area. Recently issues such as peri- or even preconceptional nutrition, transgenerational effects and underlying mechanisms have received considerable attention. The present chapter presents the existed evidence and reviews the available data from numerous animal and human studies on the effects of early life nutritional environment on adult reproductive function. Specific outcomes depend on the severity, duration and stage of development when nutritional perturbations are imposed, while sex-specific effects are also manifested. Apart from undernutrition, effects of relative overnutrition as well as the complex interactions between pre- and postnatal nutrition is of high importance, especially in the context of our days obesity epidemic. Mechanisms underlying reproductive programming are yet unclear, but may include a role for epigenetic modifications. Epigenetic modulation of critical genes involved in the control of reproductive function and potential intergenerational effects represent an exciting area of interdisciplinary research toward the development of new nutritional approaches during pre- and postnatal periods to ensure reproductive health in later life.

For heavy metals that have any degree of transfer though the placenta to the fetus, it is unlikely that there are safe limits for maternal blood levels. The only means of reducing fetal exposure is to minimise maternal exposure. There are few recommendations for levels of concern. With the exception of US recommendations for maternal Pb levels, but there are no international levels of concern or cut-off levels specifically for pregnancy for heavy metals, so that comparisons can generally only be made with national reference values relating to similar physiological statuses or age groups. These include recommendations for Cd levels by Germany (reference value for non-smoking adults aged 18–69 years, 1 µg/l) and for Hg by Germany (reference value for adults age 18–60 years with fish intake ⩽3 times per month, 2.0 µg/l) and the USA (cut-off level for women, 5.8 µg/dl). To illustrate the lack of cohesion, we present data on blood Pb, Cd and Hg levels from pregnant women enroled in the UK Avon Longitudinal Study of Parents and Children study and compare the values with present levels of concern and recommended cut-off values. We also compare the levels with those found in other groups of pregnant women worldwide to strengthen the database for the development of levels of concern in pregnancy. The need for clarity of terminology in describing levels of concern is discussed. There is a pressing need for international consensus on levels of concern for all age groups and physiological statuses, particularly for pregnancy.

Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.

Intrauterine growth restriction (IUGR) is an important risk factor for development of hypertension, diabetes and the metabolic syndrome. Maternal low protein (LP) intake during rat pregnancy leads to IUGR in male and female offspring, although females may be resistant to the development of effect. Current evidence suggests that changes in the renin-angiotensin system (RAS) in utero contribute to this programmed hypertension, via sex-specific mechanisms. The previously orphaned G-protein coupled receptor (GPR91) was identified as a central player in the development of hypertension in adult mice, through a RAS-dependent pathway. However, whether the GPR91 pathway contributes to fetal programming is unknown. Furthermore, the nature of involvement of downstream modulators of the RAS including Gqα/11α and GαS has not been investigated in IUGR-LP rats. Therefore, we postulated that renal GPR91, in conjunction with RAS, is differentially impacted in a sex-specific manner from LP-induced IUGR rats. Pregnant Wistar rats were fed control (C, 20% protein) or LP (8% protein) diet until embryonic day 19 (E19) or postnatal d21. At E19, GPR91 protein and mRNA were increased in both male and female LP kidneys (P<0.05), whereas renin and angiotensin converting enzyme (ACE) were only increased in males (P=0.06 and P<0.05, respectively). On d21, AT1R and Gqα/11α were increased in LP males, while in LP females, AT2R protein was elevated and renin expression was decreased (P<0.05). This study demonstrates that in IUGR-LP rats, up regulation of GPR91 in fetal kidney is mirrored by increased ACE and renin in males. These in utero alterations, when combined with postnatal increases in AT1R-Gqα/11α specifically in male offspring, may predispose to the development of hypertension.

Here we analyze the outcomes of unlimited access to a low-energy (LE) diet in dams and their offspring. At 3 weeks’ gestation, pregnant Wistar rats were divided into two groups: (1) the control group received a normoenergetic diet; and (2) the experimental group received the LE diet. In dams, lactation outcomes, food intake, body weight, plasma IGF-1, prealbumin, transferrin and retinol-binding protein levels were evaluated; in offspring, biometric and biochemical parameters and food intake were evaluated. No differences were observed during pregnancy. However, after lactation, dams that received the LE diet demonstrated significant reductions in body weight (P<0.05), plasma IGF-1 (P=0.01), prealbumin and visceral fat (P<0.001). Pups born to dams that received the LE diet demonstrated reduced body length and weight at weaning (P<0.001) and were lighter than the control animals at the end of the experimental period. Pups also demonstrated reduced plasma, low-density lipoprotein (P=0.04), triglycerides (P=0.002) and glucose levels (P<0.05), and differences were noted in visceral fat. These results indicate that feeding dams with LE diet during the reproductive period induces acute malnutrition and impairs the growth and development of offspring, as well as certain metabolic parameters.

Antenatal steroid administration is associated with hypertension in adult life; however, the mechanisms underlying this phenomenon are unclear. The aim of this study was to further characterize the effects of antenatal glucocorticoid exposure on the endothelin (ET-1) system, specifically to ascertain the role of the cyclic adenosine diphosphate ribose (cADPR)/ryanodine receptor pathway in the increased sensitivity to ET-1 observed in the offspring exposed to antenatal glucocorticoids. Pregnant sheep were randomly treated with betamethasone (Beta; 0.17 mg/kg) or vehicle at 80 and 81 days of gestation. In adults, we studied endothelium-denuded arterial segments of the brachial arteries. ET-1-induced vasoconstriction was significantly higher in the arteries from Beta sheep (F=3.5, P<0.05). Inhibition of ADP-ribosyl cyclase with 2-2'-dihydroxy-azobenzene significantly decreased the ET-1-induced contraction in Beta but not in vehicle-treated sheep. Nicotinamide attenuated ET-1 contraction in both, but it was significantly more pronounced in the Beta-treated sheep. No significant differences were observed following KCl-induced (6.25–75 mM) contraction. Nicotinamide (10 mM) significantly attenuated the KCl-induced vasoconstriction in both groups. In KCl (62.5 mM)-constricted arteries, the effect of nicotinamide (NIC) was significantly greater in the vehicle-treated sheep (50% relaxation v. 40% relaxation; t=2.2, P<0.05). In contrast, the sodium nitroprusside (SNP) relaxation was not statistically different. An additive effect was observed when NIC and SNP were used in combination and it was also more pronounced in vehicle-treated sheep. We conclude that the increased response to ET-1 is mediated by activation of the CD38/cADPR signaling pathway. Further studies are required to identify the effectors downstream from cADPR affected by exposure to antenatal steroids.

Pregnancy is a special condition where many metabolic changes may occur because of increased requirement of essential micronutrients such as iron and iodine. Foetal thyroid starts producing its own thyroid hormones after 12 weeks of gestation. Therefore, the first trimester is very crucial for meeting thyroid hormone requirements of the mother and foetus. Iodine deficiency and iron deficiency may affect mental and physical growth of the foetus. Hence, it is very important to establish a programme on the screening of pregnant women for thyroid dysfunction tests along with established iron status assessment. Thus, the study was aimed to screen the pregnant women for iodine deficiency disorders and iron deficiency during early gestation, situational analysis on thyroid insufficiency and iron deficiency in pregnant women (gestational age <15 weeks) in urban Vadodara, Gujarat. n = 256 healthy pregnant women with uncomplicated singleton pregnancy were selected. The thyroid hormone was estimated by RIA, UIE using simple microplate technique and haemoglobin (Hb) concentration by acid hematin method. Median thyrotropin (TSH), free thyroxine (FT4), total thyroxine (TT4) and UIE concentrations were 1.88 μIU/ml, 0.83 ng/dl, 10.24 μg/dl and 297.14 mcg/l, respectively. There was a significant correlation between TSH, FT4 and month of gestation. Mean Hb concentration was 9.27 ± 1.09 g/dl. The prevalence of iodine insufficiency (based on UI) was 16.79% and iron deficiency was 91%. Screening programme for iodine deficiency during early gestation should be implemented along with the existing programme of haemoglobin estimation at first prenatal visit. This would help prevent damage to the developing brain and growth of the foetus and also to trace at-risk pregnant women.