Fetal Programming Is Deeply Related to Maternal Selenium Status and Oxidative Balance; Experimental Offspring Health Repercussions

Abstract

Nutrients consumed by mothers during pregnancy and lactation can exert permanent effects upon infant developing tissues, which could represent an important risk factor for diseases during adulthood. One of the important nutrients that contributes to regulating the cell cycle and tissue development and functionality is the trace element selenium (Se). Maternal Se requirements increase during gestation and lactation. Se performs its biological action by forming part of 25 selenoproteins, most of which have antioxidant properties, such as glutathione peroxidases (GPxs) and selenoprotein P (SELENOP). These are also related to endocrine regulation, appetite, growth and energy homeostasis. In experimental studies, it has been found that low dietary maternal Se supply leads to an important oxidative disruption in dams and in their progeny. This oxidative stress deeply affects gestational parameters, and leads to intrauterine growth retardation and abnormal development of tissues, which is related to endocrine metabolic imbalance. Childhood pathologies related to oxidative stress during pregnancy and/or lactation, leading to metabolic programing disorders like fetal alcohol spectrum disorders (FASD), have been associated with a low maternal Se status and intrauterine growth retardation. In this context, Se supplementation therapy to alcoholic dams avoids growth retardation, hepatic oxidation and improves gestational and breastfeeding parameters in FASD pups. This review is focused on the important role that Se plays during intrauterine and breastfeeding development, in order to highlight it as a marker and/or a nutritional strategy to avoid diverse fetal programming disorders related to oxidative stress.

Selenoproteins in the Human Placenta: How Essential Is Selenium to a Healthy Start to Life?

“…The expression of GPx2 has recently been investigated in developing mouse embryos, where expression of GPx2 mRNA was higher in the extraembryonic tissues than in the embryo [ 36 , 60 ]. In the embryo, expression was spatiotemporally regulated, indicating that GPx2 may be important for organogenesis and foetal development; however, the cell- and tissue-specific functions were not identified [ 38 ].…”

“…GPx3, the extracellular plasma enzyme, has been demonstrated to play a role in maternal–foetal selenium transfer mechanisms, important in pregnancy and birth, in pre-eclampsia and in the growth of large healthy follicles [ 36 ]. Maternal selenoproteins GPx and Selenoprotein P (SelP) were identified in apical vesicles in the epithelial cells in the d-13 visceral yolk sac [ 70 ].…”

“…GPx4 is found in placental tissue and is vital for embryonic development and male fertility [ 16 , 36 ]. GPx4 knockout mice are non-viable, and embryos die by gestational day E 8.5, suggesting an important fundamental role of GPx4 in development.…”

“…GPx4 knockout mice are non-viable, and embryos die by gestational day E 8.5, suggesting an important fundamental role of GPx4 in development. Moreover, GPx4 is also related to the activation of the transcription factor essential for inflammatory responses, nuclear factor-kB, where dysfunctional NF-kB expression causes embryonic mortality around gestational day E-15 [ 36 ]. More recently, in primary human trophoblasts and mouse pregnancies, it was found that preterm birth was associated with ferroptosis, which is a regulated non-apoptotic form of cell death [ 72 , 73 ].…”

The Role of Selenoprotein Tissue Homeostasis in MetS Programming: Energy Balance and Cardiometabolic Implications

“…Twenty-five selenoproteins are recognized in humans, with different biological functions ( Table 1 ) [ 34 , 35 ], such as iodothyronine deiodinases (DIOs: 1, 2, and 3 families), responsible for thyroid function; or thioredoxin reductases (TXNRD1, 2, and 3), SelW, SelH, SelT, and SelV, involved in redox regulation processes [ 36 ]. However, most of them have antioxidant properties, like the glutathione peroxidases family (GPxs: GPx1–GPx8), which eliminate the excess of H 2 O 2 , and selenoprotein P (SelP), the main serum Se transporter [ 2 ].…”