Imprinted gene expression in the rat embryo-fetal axis is altered in response to periconceptional maternal low
Wing Yee Kwong1, Daniel J Miller, Elizabeth Ursell
1School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. wyk@soton.ac.uk
Insights
Maternal low protein diet during early pregnancy programs imprinted gene expression, impacting male fetal growth. This gender-specific effect originates in the preimplantation embryo, influencing postnatal development.
Area of Science:
- Developmental Biology
- Genetics
- Nutritional Science
Background:
- Maternal low protein diet (LPD) during the preimplantation period causes gender-specific low birth weight and hypertension.
- The impact of LPD timing on fetal development and imprinted gene expression requires further investigation.
Purpose of the Study:
- To investigate the effects of maternal LPD, restricted to the preimplantation period or throughout gestation, on fetal growth and imprinted gene expression.
- To determine if LPD-induced alterations in gene expression originate during the preimplantation stage.
Main Methods:
- Rats were fed a low protein diet (LPD) exclusively during the preimplantation period or throughout gestation.
- Gene expression (H19, Igf2, Igf2R mRNA) and DNA methylation were analyzed in blastocysts, fetal liver, and placenta.
- Fetal growth parameters were assessed.
Main Results:
- Male blastocysts from LPD dams showed a 30% reduction in H19 mRNA.
- Male fetal liver (day 20) exhibited reduced H19 (9.4%) and Igf2 (10.9%) mRNA with preimplantation LPD, but not with LPD throughout gestation.
- No significant changes in Igf2R expression or H19 methylation were observed.
- Placental gene expression remained unaffected by LPD treatments.
Conclusions:
- Periconceptional maternal LPD can induce gender-specific programming of imprinted gene expression within the preimplantation embryo.
- This embryonic programming contributes to altered postnatal growth and development.
- Dietary intervention timing is critical for mitigating LPD-induced developmental effects.
Abstract:
In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) in H19 mRNA level. A significant reduction in H19 (9.4%) and Igf2 (10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression of Igf2R was observed in relation to maternal diet. The reduction in H19 mRNA expression did not correlate with an observed alteration in DNA methylation at the H19 differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or female H19 and Igf2 imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affected H19 and Igf2 imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself.
