The Effect and Potential Mechanism of Maternal Micronutrient Intake on Offspring Glucose Metabolism: An Emerging Field

Diabetes has become the most common metabolic disease around the world. In addition to genetic and environmental factors in adulthood, the early life environment is critical to the progression of diabetes in adults, especially the environment during the fetal period; this concept is called “fetal programming.” Substantial evidence has illustrated the key role of early life macronutrient in programming metabolic diseases. Recently, the effect of maternal micronutrient intake on offspring glucose metabolism during later life has become an emerging field. This review focuses on updated human and animal evidence about the effect of maternal micronutrient status on offspring glucose metabolism and the underlying mechanism.

Methylome-wide association study of early life stressors and adult mental health reveals a relationship between birth date and cell type composition in blood

The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes in adulthood are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive data on genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27 × 10 −9). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35 × 10−8). Genes and gene-sets annotated from associated CpGs sites and methylation profile scores were then used to quantify any overlap between the early life environment and mental health traits. However, there was no evidence of any overlap after applying a correction for multiple testing. Time of year of birth was found to be associated with a significant difference in estimated lymphocyte and neutrophil counts. Early life environments influence the risk of developing mental health disorders later in life; however, this study provides no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.

Feto-Maternal Crosstalk in the Development of the Circadian Clock System

The circadian (24 h) clock system adapts physiology and behavior to daily recurring changes in the environment. Compared to the extensive knowledge assembled over the last decades on the circadian system in adults, its regulation and function during development is still largely obscure. It has been shown that environmental factors, such as stress or alterations in photoperiod, disrupt maternal neuroendocrine homeostasis and program the offspring’s circadian function. However, the process of circadian differentiation cannot be fully dependent on maternal rhythms alone, since circadian rhythms in offspring from mothers lacking a functional clock (due to SCN lesioning or genetic clock deletion) develop normally. This mini-review focuses on recent findings suggesting that the embryo/fetal molecular clock machinery is present and functional in several tissues early during gestation. It is entrained by maternal rhythmic signals crossing the placenta while itself controlling responsiveness to such external factors to certain times of the day. The elucidation of the molecular mechanisms through which maternal, placental and embryo/fetal clocks interact with each other, sense, integrate and coordinate signals from the early life environment is improving our understanding of how the circadian system emerges during development and how it affects physiological resilience against external perturbations during this critical time period.

Maternal High-Fiber Diet Protects Offspring against Type 2 Diabetes

Previous studies have reported that maternal malnutrition is linked to increased risk of developing type 2 diabetes in adulthood. Although several diabetic risk factors associated with early-life environment have been identified, protective factors remain elusive. Here, we conducted a longitudinal study with 671 Nile rats whereby we examined the interplay between early-life environment (maternal diet) and later-life environment (offspring diet) using opposing diets that induce or prevent diet-induced diabetes. Specifically, we modulated the early-life environment throughout oogenesis, pregnancy, and nursing by feeding Nile rat dams a lifelong high-fiber diet to investigate whether the offspring are protected from type 2 diabetes. We found that exposure to a high-fiber maternal diet prior to weaning significantly lowered the risk of diet-induced diabetes in the offspring. Interestingly, offspring consuming a high-fiber diet after weaning did not develop diet-induced diabetes, even when exposed to a diabetogenic maternal diet. Here, we provide the first evidence that the protective effect of a high-fiber diet can be transmitted to the offspring through the maternal diet, which has important implications in diabetes prevention.

Maternal High Fiber Diet Protects Offspring Against Type 2 Diabetes

Previous studies have reported that maternal malnutrition is linked to increased risk of developing type 2 diabetes in adulthood. Although several diabetic risk factors associated with early life environment have been identified, protective factors remain elusive. Here, we modulate the early life environment using a maternal high fiber diet to investigate whether the offspring are protected from type 2 diabetes. We examined the interplay between early life environment (maternal diet) and later life environment (offspring diet) using a longitudinal study with 671 Nile rats. We found that exposure to a high fiber maternal diet prior to weaning significantly lowers the risk of diet-induced diabetes in the offspring. Interestingly, offspring consuming a high fiber diet after weaning do not get diet-induced diabetes, even when exposed to a diabetogenic maternal diet. Here, we provide the first evidence that the protective effect of high fiber can be transmitted to the offspring through a maternal diet, which has important implications in diabetes prevention.

Early-life environment programs reproductive strategies through epigenetic regulation of SRD5A1

Reproductive function and duration of the reproductive life span are phenotypically plastic and programmed in response to the early-life environment. Such adaptive responses are described and rationalized in life history theory in the context of resource availability, but the molecular mechanisms responsible have remained enigmatic. In this study, we hypothesized that epigenetic modifications underlie adaptive reproductive strategies, and found distinct methylation patterns in buccal DNA of Bangladeshi women who grew up in Bangladesh or the UK. The later pubertal onset and lower ovarian reserve associated with Bangladeshi childhood was seen to correlate with more numerous childhood infections, so we adopted a mouse model of pre-pubertal colitis to mimic these conditions. These mice have a similarly-altered reproductive phenotype, which enabled us to determine its mechanistic basis. Several genes encoding proteins with known functions in follicle recruitment were differentially expressed in the mice ovaries, and were also differentially methylated in the women’s buccal DNA. One of these, SRD5A1 which encodes the steroidogenic enzyme 5α reductase-1, was down-regulated in the mice ovaries and hyper methylated at the same putative transcriptional enhancer as in the women’s DNA; the levels of methylation correlating with gene expression levels. Srd5a1 expression was down-regulated also in the hypothalamus where 5α reductase-1 catalyzes production of neurosteroids that regulate gonadotropin releasing hormone (GnRH). Chemical inhibition of this enzyme affected both GnRH synthesis and release, and resulted in delayed pubertal onset in vivo. The activity of 5α reductase-1 in hypothalamus and ovary and the sensitivity of SRD5A1 to epigenetic regulation attest to its role in directing long-term physiological strategies in response to environmental conditions. In the reproductive axis, this includes timing of pubertal onset, adult reproductive function and duration of the reproductive lifespan.