Genomic imprinting, growth and maternal–fetal interactions

Abstract

In the 1980s, mouse nuclear transplantation experiments revealed that both male and female parental genomes are required for successful development to term (McGrath and Solter, 1983; Surani and Barton, 1983). This non-equivalence of parental genomes is because imprinted genes are predominantly expressed from only one parental chromosome. Uniparental inheritance of these genomic regions causes paediatric growth disorders such as Beckwith–Wiedemann and Silver–Russell syndromes (reviewed in Peters, 2014). More than 100 imprinted genes have now been discovered and the functions of many of these genes have been assessed in murine models. The first such genes described were the fetal growth factor insulin-like growth factor 2 (Igf2) and its inhibitor Igf2 receptor (Igf2r) (DeChiara et al., 1991; Lau et al., 1994; Wang et al., 1994). Since then, it has emerged that most imprinted genes modulate fetal growth and resource acquisition in a variety of ways. First, imprinted genes are required for the development of a functional placenta, the organ that mediates the exchange of nutrients between mother and fetus. Second, these genes act in an embryo-autonomous manner to affect the growth rate and organogenesis. Finally, imprinted genes can signal the nutritional status between mother and fetus, and can modulate levels of maternal care. Importantly, many imprinted genes have been shown to affect postnatal growth and energy homeostasis. Given that abnormal birthweight correlates with adverse adult metabolic health, including obesity and cardiovascular disease, it is crucial to understand how the modulation of this dosage-sensitive, epigenetically regulated class of genes can contribute to fetal and postnatal growth, with implications for lifelong health and disease.

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

“…In line with these findings, meta-analytic data report a decrease in the sperm H19-IGF2 methylation rate in infertile patients compared to fertile controls [35]. Importantly, methylation of imprinted genes is inherited by the embryo [26] and, therefore, this abnormality can be transmitted to the offspring.…”

“…Accordingly, the involvement of imprinted genes in embryo and placenta development and growth is well acknowledged in mice. Commonly, paternally-imprinted genes are believed to act as embryo/fetal-growth promoters, while, conversely, maternally-imprinted ones oppose the embryo's growth [26]. Transcription is first detectable in the male pronucleus and, in humans, a transcription burst happens between the four-cell and eight-cell embryo stages, when the embryo gene activation (EGA) starts [15].…”

“…The role of imprinted genes in processes involved in embryo and placenta development and growth is well recognized in mice. Given that the Igf2 murine gene encodes for a growth factor promoting fetal and placental growth [26], the amount of the sperm-derived IGF2 transcript released into the human oocyte after sperm-oocyte fusion may influence the embryo morphokinetics. Accordingly, as previously summarized, preimplantation embryo development is only sustained by the sperm and oocyte-derived transcriptomes and proteome before EGA, since the human embryo transcription burst occurs only between the four-cell and eight-cell embryo stages [21].…”

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

“…Given the presence of G-protein-related receptors in fetal tissues, melatonin directly modulates adrenal cortisol production and lipolysis in brown adipose tissue [23,24]. Genetic and epigenetic factors that act prenatally can modulate processes associated with obesity, including hypothalamic neuropeptides and glucocorticoid receptors [25][26][27][28][29]. Epigenetic modifications in the histone (H3K4) structure of the hepatic insulin-like growth factor (IGF) lead to increase of IGF-1 levels in the blood of delayed fetuses, which "programs" their catch-up growth in the first months of life [30,31].…”

Role of the maternal melatonin circadian rhythm absence in early catch-up growth in children

“…в перинатальном периоде. Так, установлены особенности экспрессии генов, участвующих в контроле дифференцировки и функционирования клеток жировой ткани, печени, а также гипоталамических нейропептидов и глюкокортикоидных рецепторов в генезе скачка роста [37][38][39][40][41]. Эпигенетические модификации структуры гистона (Н3К4) инсулиноподобного ростового фактора в печени ведут к повышению в крови отставших в развитии плодов уровня ИФр-1, что предопределяет у них скачок роста в первые месяцы жизни [42,43].…”