Maternal Protein Restriction in Rats Alters the Expression of Genes Involved in Mitochondrial Metabolism and Epitranscriptomics in Fetal Hypothalamus

Overview

Journal Nutrients

Date 2020 May 23

PMID 32438566

Citations 6

Authors

Morgane Frapin

Simon Guignard

Dimitri Meistermann

Isabelle Grit

Valentine S Moulle

Vincent Paille

Patricia Parnet

Valerie Amarger

Affiliations

Soon will be listed here.

Abstract

Fetal brain development is closely dependent on maternal nutrition and metabolic status. Maternal protein restriction (PR) is known to be associated with alterations in the structure and function of the hypothalamus, leading to impaired control of energy homeostasis and food intake. The objective of this study was to identify the cellular and molecular systems underlying these effects during fetal development. We combined a global transcriptomic analysis on the fetal hypothalamus from a rat model of maternal PR with in vitro neurosphere culture and cellular analyses. Several genes encoding proteins from the mitochondrial respiratory chain complexes were overexpressed in the PR group and mitochondrial metabolic activity in the fetal hypothalamus was altered. The level of the N6-methyladenosine epitranscriptomic mark was reduced in the PR fetuses, and the expression of several genes involved in the writing/erasing/reading of this mark was indeed altered, as well as genes encoding several RNA-binding proteins. Additionally, we observed a higher number of neuronal-committed progenitors at embryonic day 17 (E17) in the PR fetuses. Together, these data strongly suggest a metabolic adaptation to the amino acid shortage, combined with the post-transcriptional control of protein expression, which might reflect alterations in the control of the timing of neuronal progenitor differentiation.

Citing Articles

m1A regulator‑mediated methylation modifications and gene signatures and their prognostic value in multiple myeloma.

Fu J, Han X, Gao W, Yu M, Cui X Exp Ther Med. 2024; 29(1):18.

PMID: 39624591 PMC: 11609613. DOI: 10.3892/etm.2024.12768.

Unraveling the Molecular Mechanisms of the Neurodevelopmental Consequences of Fetal Protein Deficiency: Insights From Rodent Models and Public Health Implications.

Vancamp P, Frapin M, Parnet P, Amarger V Biol Psychiatry Glob Open Sci. 2024; 4(5):100339.

PMID: 39040432 PMC: 11262180. DOI: 10.1016/j.bpsgos.2024.100339.

Immunisation of the somatostatin gene alters hypothalamic-pituitary-liver gene expressions and enhances growth in Dazu black goats.

Qin G, Fang S, Song X, Zhang L, Huang J, Huang Y Anim Biosci. 2024; 37(11):1987-1999.

PMID: 38938026 PMC: 11541029. DOI: 10.5713/ab.24.0121.

Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring.

Moulle V, Frapin M, Amarger V, Parnet P Nutrients. 2023; 15(2).

PMID: 36678336 PMC: 9863736. DOI: 10.3390/nu15020463.

Nutrition for Brain Development.

Mohajeri M Nutrients. 2022; 14(7).

PMID: 35406032 PMC: 9003088. DOI: 10.3390/nu14071419.

References

Tsujimura K, Abematsu M, Kohyama J, Namihira M, Nakashima K . Neuronal differentiation of neural precursor cells is promoted by the methyl-CpG-binding protein MeCP2. Exp Neurol. 2009; 219(1):104-11. DOI: 10.1016/j.expneurol.2009.05.001. View

Lee H, Bartsch D, Xiao C, Guerrero S, Ahuja G, Schindler C . A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat Commun. 2017; 8(1):1456. PMC: 5682285. DOI: 10.1038/s41467-017-01744-5. View

Lee K, Hwang S, Lee J . Neuronal autophagy and neurodevelopmental disorders. Exp Neurobiol. 2013; 22(3):133-42. PMC: 3807000. DOI: 10.5607/en.2013.22.3.133. View

Sevrin T, Alexandre-Gouabau M, Castellano B, Aguesse A, Ouguerram K, Ngyuen P . Impact of Fenugreek on Milk Production in Rodent Models of Lactation Challenge. Nutrients. 2019; 11(11). PMC: 6893785. DOI: 10.3390/nu11112571. View

. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2018; 47(D1):D506-D515. PMC: 6323992. DOI: 10.1093/nar/gky1049. View

Sanosaka T, Namihira M, Nakashima K . Epigenetic mechanisms in sequential differentiation of neural stem cells. Epigenetics. 2009; 4(2):89-92. DOI: 10.4161/epi.4.2.8233. View

Juliandi B, Abematsu M, Nakashima K . Epigenetic regulation in neural stem cell differentiation. Dev Growth Differ. 2010; 52(6):493-504. DOI: 10.1111/j.1440-169X.2010.01175.x. View

Amarger V, Lecouillard A, Ancellet L, Grit I, Castellano B, Hulin P . Protein content and methyl donors in maternal diet interact to influence the proliferation rate and cell fate of neural stem cells in rat hippocampus. Nutrients. 2014; 6(10):4200-17. PMC: 4210914. DOI: 10.3390/nu6104200. View

Sibley C, Brownbill P, Dilworth M, Glazier J . Review: Adaptation in placental nutrient supply to meet fetal growth demand: implications for programming. Placenta. 2010; 31 Suppl:S70-4. DOI: 10.1016/j.placenta.2009.12.020. View

10.

Ferreira D, Pedroza A, Braz G, Fernandes M, Lagranha C . Mitochondrial dysfunction: maternal protein restriction as a trigger of reactive species overproduction and brainstem energy failure in male offspring brainstem. Nutr Neurosci. 2018; 22(11):778-788. DOI: 10.1080/1028415X.2018.1444543. View

11.

Imayoshi I, Kageyama R . bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells. Neuron. 2014; 82(1):9-23. DOI: 10.1016/j.neuron.2014.03.018. View

12.

Martin Agnoux A, Antignac J, Simard G, Poupeau G, Darmaun D, Parnet P . Time window-dependent effect of perinatal maternal protein restriction on insulin sensitivity and energy substrate oxidation in adult male offspring. Am J Physiol Regul Integr Comp Physiol. 2014; 307(2):R184-97. DOI: 10.1152/ajpregu.00015.2014. View

13.

Niu X, Zhao Y, Yang N, Zhao X, Zhang W, Bai X . Proteasome activation by insulin-like growth factor-1/nuclear factor erythroid 2-related factor 2 signaling promotes exercise-induced neurogenesis. Stem Cells. 2019; 38(2):246-260. DOI: 10.1002/stem.3102. View

14.

Gotz M, Huttner W . The cell biology of neurogenesis. Nat Rev Mol Cell Biol. 2005; 6(10):777-88. DOI: 10.1038/nrm1739. View

15.

Gaignard P, Frechou M, Liere P, Therond P, Schumacher M, Slama A . Sex differences in brain mitochondrial metabolism: influence of endogenous steroids and stroke. J Neuroendocrinol. 2017; 30(2). DOI: 10.1111/jne.12497. View

16.

Guevara R, Santandreu F, Valle A, Gianotti M, Oliver J, Roca P . Sex-dependent differences in aged rat brain mitochondrial function and oxidative stress. Free Radic Biol Med. 2008; 46(2):169-75. DOI: 10.1016/j.freeradbiomed.2008.09.035. View

17.

Baser A, Skabkin M, Kleber S, Dang Y, Gulculer Balta G, Kalamakis G . Onset of differentiation is post-transcriptionally controlled in adult neural stem cells. Nature. 2019; 566(7742):100-104. DOI: 10.1038/s41586-019-0888-x. View

18.

Tran N, Amarger V, Bourdon A, Misbert E, Grit I, Winer N . Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors. J Matern Fetal Neonatal Med. 2016; 30(16):1906-1911. DOI: 10.1080/14767058.2016.1229768. View

19.

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

20.

Gomes L, Benedetto G, Scorrano L . During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol. 2011; 13(5):589-98. PMC: 3088644. DOI: 10.1038/ncb2220. View