Parental diet, pregnancy outcomes and offspring health: metabolic determinants in developing oocytes and embryos

Abstract

The periconceptional period, embracing the terminal stages of oocyte growth and post-fertilisation development up to implantation, is sensitive to parental nutrition. Deficiencies or excesses in a range of macro- and micronutrients during this period can lead to impairments in fertility, fetal development and long-term offspring health. Obesity and genotype-related differences in regional adiposity are associated with impaired liver function and insulin resistance, and contribute to fatty acid-mediated impairments in sperm viability and oocyte and embryo quality, all of which are associated with endoplasmic reticulum stress and compromised fertility. Disturbances to maternal protein metabolism can elevate ammonium concentrations in reproductive tissues and disturb embryo and fetal development. Associated with this are disturbances to one-carbon metabolism, which can lead to epigenetic modifications to DNA and associated proteins in offspring that are both insulin resistant and hypertensive. Many enzymes involved in epigenetic gene regulation use metabolic cosubstrates (e.g. acetyl CoA and S-adenosyl methionine) to modify DNA and associated proteins, and so act as 'metabolic sensors' providing a link between parental nutritional status and gene regulation. Separate to their genomic contribution, spermatozoa can also influence embryo development via direct interactions with the egg and by seminal plasma components that act on oviductal and uterine tissues.

Cannabinoid receptor signaling regulates liver development and metabolism

“…Each developmental stage may require the implementation of specific metabolic programs, and defects in metabolic processing or nutrient utilization could disrupt the differentiation and function of essential organs (Shyh-Chang et al, 2013). Alterations in developmental metabolism may also impact adult organ function through direct regulation of essential acetylation and methylation processes to alter the epigenetic control of development (Shyh-Chang et al, 2013;Sinclair and Watkins, 2014). Impairment of cellular proliferation pathways can disrupt organogenesis, thereby inhibiting normal physiological functions and leading to long-term consequences for adult metabolic homeostasis.…”

Early-life nutritional effects on the female reproductive system

“…In this regard, epidemiological and experimental data have indicated that there is a relationship between the in utero environment and the risk of developing chronic disease later in life (Gluckman & Hanson 2004. A number of differential insults that induce developmental adaptations have been shown to modify disease risk (Champagne 2011, Rosenfeld 2012, Desai et al 2013, Reynolds 2013, Sinclair & Watkins 2013, Tarantal & Berglund 2014 and to modulate reproductive function (Savabieasfahani et al 2006, Sloboda et al 2009, Connor et al 2012, Schöpper et al 2012, Lie et al 2013, Barra et al 2014. As the gametes that will eventually give rise to grand-offspring form during fetal life, it is possible that the link between early-life adversity and postnatal disease lies in the developing ovary -involving the developing germ cells and their function.…”

Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk

“…Although it has been well established in both clinical (93) and basic animal studies (4) that that periconceptual period is equally (and some might argue more) important in establishing long-term health and disease risk in offspring, no data currently exist describing the periconceptional maternal microbiome. Although it has been reported that first trimester pregnant microbiome is similar to that of the non-pregnant microbiome and shifts appear to occur predominantly in the third trimester (57,58), it is unknown whether the periconceptional period presents a window of opportunity for microbial intervention.…”

“…In this regard, epidemiological and experimental data have inextricably shown a relationship between the in utero environment and the risk of developing chronic disease later in life (3). A multitude of "modifying" cues inducing developmental adaptations that impact on disease risk have been identified (4,5). Most recently, research into the gut microbiota has become one of most studied factors influencing disease risk.…”