Skip to main content
Log in

In vivo: maternal betaine supplementation normalized fetal growth in diabetic pregnancy

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Diabetes alters maternal metabolism and can lead to aberrant fetal growth. In addition to insulin treatment, nutritional diet interventions are recommended for promoting fetal health against diabetes-induced adverse effects. Therefore, we conducted an in vivo study to investigate betaine efficacy on fetal development against maternal diabetes.

Methods

Thirty-two dams were divided into four equal groups: control (C), betaine supplementation (BS), diabetic pregnancy (DP) and diabetic pregnancy plus betaine supplementation (DP + BS). Fasting blood sugar (FBS) and body weight (BW) were monitored during pregnancy. After physiological delivery, dams glycated hemoglobin (HbA1c) concentrations were measured, followed by fetal development indices including litter size (LS), neonatal weight (NW) and crown-rump (CR). Also, maternal oxidative status was assessed by evaluating glutathione (GSH) content, glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and malondialdehyde (MDA) concentration in the erythrocytes.

Results

Betaine supplementation significantly alleviated FBS and tended to recover BW loss. It also significantly decreased HbA1c values in dams of DP + BS compared to DP group. Normalized fetal indices such as LS, NW and CR under betaine supplementation were associated with a significant increase in GSH content and GSH-Px activity, as well as decreased MDA concentrations in erythrocytes of dams in the DP + BS versus the DP group, indicating improved redox balance in the dams.

Conclusion

We indicated for the first time that betaine supplementation improved the maternal glucose metabolism and redox balance associated with normalized fetal growth. Nevertheless, further studies are required to investigate the mechanisms through which betaine protects fetal growth in diabetic pregnancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Alirezaei M, Jelodar G, Niknam P, Khoshdel Z, Yavari M (2014) Nutritional effects of betaine on weight and length of rat offspring. Comp Clin Pathol 23(3):551–556

    Article  CAS  Google Scholar 

  2. Alirezaei M, Khoshdel Z, Dezfoulian O, Rashidipour M, Taghadosi V (2015) Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats. J Physiol Sci 65(3):243–252

    Article  CAS  Google Scholar 

  3. Alirezaei M, Kheradmand A, Salahi P, Azizi A (2018) Olive leaves extract effects on sperm quality following experimentally-induced diabetes in rats. Iran J Vet Med 12(4):335–346

    Google Scholar 

  4. Aref A, Ahmed O, Ali L, Semmler M (2013) Maternal rat diabetes mellitus deleteriously affects insulin sensitivity and beta-cell function in the offspring. J Diabetes Res. https://doi.org/10.1155/2013/429154

    Article  PubMed  PubMed Central  Google Scholar 

  5. Aziz A, Hajar S, John CM et al (2016) Animal model of gestational diabetes mellitus with pathophysiological resemblance to the human condition induced by multiple factors (nutritional, pharmacological, and stress) in rats. Biomed Res Int. https://doi.org/10.1155/2016/9704607

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cederberg J, Siman C, Eriksson U (2001) Combined treatment with vitamin e and vitamin C decreases oxidative stress and improves fetal outcome in experimental diabetic pregnancy. Pediatr Res 49(6):755–762

    Article  CAS  Google Scholar 

  7. Chen Q, Francis E, Hu G, Chen L (2018) Metabolomic profiling of women with gestational diabetes mellitus and their offspring: review of metabolomics studies. J Diabetes Complicat 32(5):512–523

    Article  Google Scholar 

  8. Craig SAS (2004) Betaine in human nutrition. Am J Clin Nutr 80(3):539–549

    Article  CAS  Google Scholar 

  9. Damasceno DC, Netto AO, Lessi IL, Gallego FQ, Corvino SB, Dallaqua B, Sinzato YK, Bueno A, Calderon IMP, Rudge MVC (2018) Streptozotocin-induced diabetes models: pathophysiological mechanisms and fetal outcomes. Biomed Res Int. https://doi.org/10.1155/2014/819065

    Article  Google Scholar 

  10. Du J, Shen L, Tan Z et al (2018) Betaine supplementation enhances lipid metabolism and improves insulin resistance in mice fed a high-fat diet. Nutrients. https://doi.org/10.3390/nu10020131

    Article  PubMed  PubMed Central  Google Scholar 

  11. Elizabeth KE, Ashok A, Sobhakumar S, Sujatha TL (2018) Large and small-for-gestational-age (LGA and SGA) babies born to mothers with pre-pregnancy/gestational diabetes mellitus (PPDM/GDM) vs. no-DM. Acta Sci Paediatr 1(3):23–28

    Google Scholar 

  12. Eriksson RS, Thunberg L, Eriksson UJ (1989) Effects of interrupted insulin treatment on fetal outcome of pregnant diabetic rats. Diabetes 38(6):764–772

    Article  CAS  Google Scholar 

  13. Eriksson UJ (2009) Congenital anomalies in diabetic pregnancy. Semin Fetal Neonatal Med 14(2):85–93

    Article  Google Scholar 

  14. Federico C, Pridjian G (2018) An overview of gestational diabetes. In: Bagchi D, Nair S (eds) Nutritional and therapeutic interventions for diabetes and metabolic syndrome, 2nd edn. Elsevier, New York, pp 155–168

    Chapter  Google Scholar 

  15. Gadhok AK, Sharma TK, Sinha M, Khunteta R, Vardey SK, Sahni P, Sankhla M (2017) Natural antioxidant vitamins status in pregnancies complicated with intrauterine growth restriction. Clin Lab 63(5):941–945

    CAS  PubMed  Google Scholar 

  16. Gutaj P, Wender-Ozegowska E (2016) Diagnosis and management of IUGR in pregnancy complicated by type 1 diabetes mellitus. Curr Diabetes Rep 16(5):39

    Article  Google Scholar 

  17. Jawerbaum A, White VJER (2010) Animal models in diabetes and pregnancy. Endocr Rev 31(5):680–701

    Article  Google Scholar 

  18. Joselit Y, Nanobashvili K, Roberts C et al (2018) Maternal betaine supplementation affects fetal growth and lipid metabolism of high fat fed mice in a temporal-specific manner. Nutr Diabetes. https://doi.org/10.1038/s41387-018-0035-z

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kajszczarek K, Perzyńska I, Robak J, Billewicz-Kraczkowska A, Pedrycz A, Smoleń A, Kraczkowski JJ (2018) Impact of experimental diabetes and chronic hypoxia on rat fetal body weight. Ginekol Pol 89(1):20–24

    Article  Google Scholar 

  20. Kathirvel E, Morgan K, Nandgiri G, Sandoval BC, Caudill MA, Bottiglieri T, French SW, Morgan TR (2010) Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine. Am J Physiol Gastrointest Liver Physiol 299(5):1068–1077

    Article  Google Scholar 

  21. King J, Kwan S, Yan J, Klatt KC, Jiang X, Roberson MS, Caudill MA (2017) Maternal choline supplementation alters fetal growth patterns in a mouse model of placental insufficiency. Nutrients. https://doi.org/10.3390/nu9070765

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kiss A, Lima P, Sinzato Y et al (2009) Animal models for clinical and gestational diabetes: maternal and fetal outcomes. Diabetol Metab Syndr. https://doi.org/10.1186/1758-5996-1-21

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lever M, Slow S, McGregor DO, Dellow WJ, George PM, Chambers ST (2012) Variability of plasma and urine betaine in diabetes mellitus and its relationship to methionine load test responses: an observational study. Cardiovasc Diabetol. https://doi.org/10.1186/1475-2840-11-34

    Article  PubMed  PubMed Central  Google Scholar 

  24. Li X, Qinwei S, Li Xian, Cai Demin, Sui Shiyan, Jia Yimin, Song Haogang, Zhao Ruqian (2014) Dietary betaine supplementation to gestational sows enhances hippocampal IGF2 expression in newborn piglets with modified DNA methylation of the differentially methylated regions. Eur J Nutr 54(7):1201–1210

    Article  Google Scholar 

  25. Lin G, Wang X, Wu G (2014) Improving amino acid nutrition to prevent intrauterine growth restriction in mammals. Amino Acids 46(7):1605–1623

    Article  CAS  Google Scholar 

  26. Negrato C, Mattar R, Gomez M (2012) Adverse pregnancy outcomes in women with diabetes. Diabetol Metab Syndr. https://doi.org/10.1186/1758-5996-4-41

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rains J, Jain S (2011) Oxidative stress, insulin signaling and diabetes. Free Radic Biol Med 50(5):567–575

    Article  CAS  Google Scholar 

  28. Rashid C, Bansal A, Simmons R (2018) Oxidative stress, intrauterine growth restriction, and developmental programming of type 2 diabetes. Physiology 33(5):348–359

    Article  CAS  Google Scholar 

  29. Rueangdetnarong H, Sekararithi R, Jaiwongkam T, Kumfu S, Chattipakorn N, Tongsong T, Jatavan P (2018) Comparisons of the oxidative stress biomarkers levels in gestational diabetes mellitus (GDM) and non-GDM among Thai population: cohort study. Endocr Connect 7(5):681–687

    Article  CAS  Google Scholar 

  30. Saleh J (2015) Glycated hemoglobin and its spinoffs: cardiovascular disease markers or risk factors? World J Cardiol 7(8):449–453

    Article  Google Scholar 

  31. Sinzato Y, Bevilacqua E, Volpato G, Hernandez-Pando RE, Rudge MVC, Damasceno DC (2018) Maternal oxidative stress, placental morphometry, and fetal growth in diabetic rats exposed to cigarette smoke. Reprod Sci. https://doi.org/10.1177/1933719118815589

    Article  PubMed  Google Scholar 

  32. Sulaiman S, Blasio M, Harland M, Gatford KL, Owens JA (2017) Maternal methyl donor and cofactor supplementation in late pregnancy increases β-cell numbers at 16 days of life in growth-restricted twin lambs. Am J Physiol Endocrinol Metab 313(4):381–390

    Article  Google Scholar 

  33. Thompson L, Al-Hasan Y (2012) Impact of oxidative stress in fetal programming. J Pregnancy. https://doi.org/10.1155/2012/582748

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ullah A, Khan A, Khan I (2016) Diabetes mellitus and oxidative stress—a concise review. Saudi Pharm Jurnal 24(4):547–553

    Google Scholar 

  35. Vambergue A, Fajardy I (2011) Consequences of gestational and pregestational diabetes on placental function and birth weight. World J Diabetes. https://doi.org/10.4239/wjd.v2.i11.196

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wu BT, Dyer RA, King DJ, Richardson KJ, Innis SM (2012) Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants. PLoS ONE. https://doi.org/10.1371/journal.pone.0043448

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr. Asghar Sepahvand, Dr. Behrooz Ezzat Pour (the manager and deputy of Razi Herbal Medicine Research Center) and Miss. Chahari for their kindly co-operation in this study.

Funding

This work was supported by research council of Lorestan University.

Author information

Authors and Affiliations

Authors

Contributions

PS performed the experiments, collected and analyzed the data and wrote the manuscript. MG performed the experiment and collected the data. AR helped with the project management, edited the manuscript and has done native English edit. MA helped with the project management, performed the quality control of data and algorithms and analyzed the data, also edited the manuscript.

Corresponding author

Correspondence to Pouya Salahi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All rats were treated humanely and in compliance with the recommendations of Animal Care Committee for the Lorestan University (Khorramabad, Iran) with approval number: LU.ECRA. 2017.4.

Informed consent

This report does not contain any studies with human participants performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 412 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salahi, P., Gharabaghi, M., Rocky, A. et al. In vivo: maternal betaine supplementation normalized fetal growth in diabetic pregnancy. Arch Gynecol Obstet 302, 837–844 (2020). https://doi.org/10.1007/s00404-020-05665-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05665-5

Keywords

Navigation