The Long-Term Effect of Maternal Iron Levels in the Second Trimester on Mild Thinness among Preschoolers: The Modifying Effect of Small for Gestational Age.

The supplementation of multiple micronutrients throughout pregnancy can reduce the risk of adverse birth outcomes and various diseases in children. However, the long-term effect of maternal multiple micronutrient levels in the second trimester on the overall development of preschoolers remains unknown. Therefore, 1017 singleton mother-infant pairs and 6-year-old preschoolers were recruited based on the China-Wuxi Birth Cohort Study. Meanwhile, information on the demographic characteristics of pregnant women and preschoolers, maternal copper, calcium, iron, magnesium, and zinc levels in whole blood during the second trimester, and neonatal outcomes, were collected. We aimed to investigate the long-term impact of maternal copper, calcium, iron, magnesium, and zinc levels in the second trimester on mild thinness among 6-year-old preschoolers, and the modifying effect of small for gestational age (SGA), within the Chinese population. Multiple logistic regression models revealed that high-level maternal iron in the second trimester reduced the risk of mild thinness [adjusted OR: 0.46 (95% CI: 0.26, 0.80)] among 6-year-old preschoolers. However, no significant association was found for the remaining four maternal essential metal elements. Additionally, the restricted cubic spline function showed that the risk of mild thinness decreased when maternal iron concentration exceeded 7.47 mmol/L in whole blood during the second trimester. Furthermore, subgroup analysis indicated that the long-term protective effect of high-level maternal iron on mild thinness was only observed in SGA infants. Summarily, high-level maternal iron in the second trimester distinctly lowers the risk of mild thinness among 6-year-old preschoolers, especially in preschoolers with birth outcomes of SGA. Our findings offer evidence for the implementation of iron supplementation in the second trimester as a preventive measure against mild thinness in children.

Paternal exposure to microcystin-LR induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in placental labyrinth.

Microcystin-leucine arginine (MC-LR) has reproductive and developmental toxicities. Previous studies indicated that gestational exposure to MC-LR induced fetal growth restriction in mice. The aim of this study was to further evaluate the effect of paternal MC-LR exposure before mating on fetal development. Male mice were intraperitoneally injected with either normal saline or MC-LR (10 µg/kg) daily for 35 days. Male mouse was then mated with female mice with 1:1 ratio. There was no significant difference on the rates of mating and pregnancy between MC-LR-exposed male mice and controls. Body weight and crown-rump length were reduced in fetuses whose fathers were exposed to MC-LR. Despite no difference on relative thickness of labyrinthine layer, cell proliferation, as measured by Ki67 immunostaining, was reduced in labyrinth layer of MC-LR-exposed mice. Moreover, blood sinusoid area in labyrinth layer was decreased in the fetus whose father was exposed to MC-LR before mating. Correspondingly, cross-sectional area of CD34-positive blood vessel in labyrinth layer was lower in fetuses whose fathers were exposed to MC-LR than in controls. These results provide evidence that paternal MC-LR exposure before mating induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in labyrinth layer.

Long-term 1-nitropyrene exposure induces endoplasmic reticulum stress and inhibits steroidogenesis in mice testes.

1-Nitropyrene (1-NP) is a representative nitro-polycyclic aromatic hydrocarbon from diesel exhaust. Recently, we found that maternal 1-NP exposure caused fetal growth retardation and disturbed cognitive development in adolescent female offspring. To investigate long-term 1-NP exposure on spermatogenesis and steroidogenesis, male mice were exposed to 1-NP (1.0 mg/kg/day) by gavage for 70 days. There was no significant difference on relative testicular weight, number of testicular apoptotic cells and epididymal sperm count between 1-NP-exposed mice and controls. Although long-term 1-NP exposure did not influence number of Leydig cells, steroidogenic genes and enzymes, including STAR, P450scc, P45017α and 17ß-HD, were downregulated in 1-NP-expoed mouse testes. Correspondingly, serum and testicular testosterone (T) levels were reduced in 1-NP-exposed mice. Additional experiment showed that testicular GRP78 mRNA and protein were upregulated by 1-NP. Testicular phospho-IRE1α and sliced xbp-1 mRNA, a downstream molecule of IRE1α, were elevated in 1-NP-exposed mice. Testicular phospho-PERK and phospho-eIF2α, a downstream molecule of PERK pathway, were increased in 1-NP-exposed mice. Testicular NOX4, a subunit of NAPDH oxidase, and HO-1, MDA, two oxidative stress markers, were increased in 1-NP-exposed mice. Testicular GSH and GSH/GSSG were decreased in 1-NP-exposed mice. These results suggest that long-term 1-NP exposure induces reactive oxygen species-evoked ER stress and disrupts steroidogenesis in mouse testes.