Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

Differential changes in serum levels of transforming growth factor beta and interleukin-17 ratio in overweight pregnant women and their fetuses after home-based exercise training

Document Type : Original Article

Authors

Mahdieh Molanuri Shamsi 1, 2
Lida Moghaddam- Banaem 3
Marzieh Moslemi 1
Farzaneh Sinapour 1
Mona Pourmohammad 3
Afsaneh Jamali 1
Raoof Negaresh 4
Sara Soudi 5
Katsuhiko Suzuki 6

1 Department of Physical Education & Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran.

2 Department of Physical Education & Sport Sciences, Yazd University, Yazd, Iran.

3 Department of Reproductive Health and Midwifery, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

4 Department of Physical Education, Farhangian University; P.O. Box 14665-889, Tehran, Iran.

5 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

6 Faculty of Sport Sciences, Waseda University, Tokorozawa, Japan.

https://doi.org/10.22122/jeoct.2025.511249.1146
Abstract
This study investigates the effect of home-based combined exercise on the transforming growth factor-β/Interleukin-17 ratio (TGF-β/IL-17) in maternal serum during the first, second, and third trimesters of pregnancy, as well as in umbilical cord blood. Thirty overweight pregnant women were randomly allocated to control and training groups. Blood samples were collected during each trimester of pregnancy and from the umbilical cord at birth. Fitness-related indicators were assessed in the mother throughout pregnancy. Newborn health indicators were measured at birth. The levels of IL-17 and TGF-β were determined using enzyme-linked immunosorbent assay (ELISA) and specialized kits. The exercise training significantly reduced TGF-β levels (p=0.011, effect size=1.22) and the TGF-β/IL-17 ratio (p=0.045, effect size=0.79) in the third trimester in mothers. Similarly, this ratio decreased in the fetus, accompanied by an increase in IL-17 levels (p = 0.038, effect size = 0.93). These immune changes were associated with improved maternal cardiovascular fitness and higher Apgar scores at 5 minutes for newborns (p<0.05). Obesity and excessive weight gain during pregnancy are linked to inflammatory responses and elevated cytokine levels, which may increase the risk of complications for the mother. This study highlights the long-term benefits of maternal exercise, evidenced by reduced inflammatory responses and improved neonatal health outcomes, as reflected in Apgar scores.

What is already known on this subject?

Various studies have confirmed the beneficial effects of physical activity on maternal health and pregnancy-related complications in both the mother and fetus. However, the immunological mechanisms underlying these changes have been less explored. Research has demonstrated alterations in cytokines following physical activity, but the changes in these cytokines and the balance achieved among them in response to different types of exercise require more detailed investigation.

 

What this study adds?

The present study confirms changes in the balance of TGF-β and IL-17 cytokines, particularly during the third trimester of pregnancy. Nevertheless, future studies should consider examining the responses of the cells producing these cytokines.

Keywords

Pregnancy
Overweight
Cytokines
Home-based exercise
Neonatal outcomes

Subjects

Acknowledgements

The authors sincerely thank all the participants in this study.

Funding

This work was supported by the Research Center of Tarbiat Modares University (TMU).

Compliance with ethical standards

Conflict of interest The authors of this research article have no financial and personal conflict of interest statement.

Ethical approval Ethical approval for the study involving pregnant participants was obtained from the Research Ethics Committee in Biomedical Studies at Tarbiat Modares University, Iran (Approval ID: IR.MODARES.REC.1399.122). All procedures were conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and the specific ethical guidelines for research involving pregnant individuals.

Written informed consent was obtained from all participants after providing detailed information about the study’s objectives, procedures, and potential risks or benefits. Participants were informed of their right to withdraw at any stage without any consequences. The exercise intervention was designed to ensure the safety of both the pregnant participants and their fetuses, following established guidelines for physical activity during pregnancy. The study was closely monitored by medical professionals to minimize any risks.

Informed consent performed

Author contributions

Conceptualization: M.M.S, L.M.B.; Methodology: M.M., F.S.; Software: M.B, A.J.; Validation: M.M.S. Formal analysis: R.N.; Investigation: S.S, K.S.; Resources: S.S, K.S.; Data curation: M.M., F.S.; Writing - original draft: M.M.S, L.M.B.; Writing – review & editing: M.M.S, L.M.B.; Visualization: M.M.S, L.M.B.; Supervision: M.M.S. Project administration: M.M.S, L.M.B.; Funding acquisition: M.M.S, L.M.B.

Acosta-Manzano, P., Coll-Risco, I., Van Poppel, M. N. M., Segura-Jiménez, V., Femia, P., Romero-Gallardo, L., . . . Aparicio, V. A. (2019). Influence of a Concurrent Exercise Training Intervention during Pregnancy on Maternal and Arterial and Venous Cord Serum Cytokines: The GESTAFIT Project. J Clin Med, 8(11). doi: https://doi.org/10.3390/jcm8111862
Amani Shalamzari, S., Agha Alinejad, H., Gharakhanlou, R., Molanouri Shamsi, M., & Talebi Badrabadi, K. (2009). The effect of body composition and physical activity on basal levels of insulin, glucose, IL-18, IL-6 & CRP and their relationship with insulin resistance. Iranian journal of endocrinology and metabolism, 11(6), 699-706.
Apgar, V. (1953). A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg, 32(4), 260-267.
Artal, R., & O'Toole, M. (2003). Guidelines of the American College of Obstetricians and Gynecologists for exercise during pregnancy and the postpartum period. Br J Sports Med, 37(1), 6-12; discussion 12. doi: https://doi.org/10.1136/bjsm.37.1.6
Baffour-Awuah, B., Pearson, M. J., Dieberg, G., Wiles, J. D., & Smart, N. A. (2023). An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications. Clinical Hypertension, 29(1), 9. doi: https://doi.org/10.1186/s40885-022-00232-3
Bernhardt, G. V., Shivappa, P., Bernhardt, K., Bhat, S., Pinto, J. R. T., Jhancy, M., & Kumar, S. (2022). Markers of inflammation in obese pregnant women: Adenosine deaminase and high sensitive C – reactive protein. European Journal of Obstetrics & Gynecology and Reproductive Biology: X, 16, 100167. doi: https://doi.org/10.1016/j.eurox.2022.100167
Bodnar, L. M., Ness, R. B., Harger, G. F., & Roberts, J. M. (2005). Inflammation and Triglycerides Partially Mediate the Effect of Prepregnancy Body Mass Index on the Risk of Preeclampsia. American Journal of Epidemiology, 162(12), 1198-1206. doi: https://doi.org/10.1093/aje/kwi334
Calder, P. C. (2010). Omega-3 fatty acids and inflammatory processes. Nutrients, 2(3), 355-374. doi: https://doi.org/10.3390/nu2030355
Catalano, P. M., & Shankar, K. (2017). Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. Bmj, 356, j1. doi: https://doi.org/10.1136/bmj.j1
Chaabene, H., Prieske, O., Herz, M., Moran, J., Höhne, J., Kliegl, R., . . . Granacher, U. (2021). Home-based exercise programmes improve physical fitness of healthy older adults: A PRISMA-compliant systematic review and meta-analysis with relevance for COVID-19. Ageing Research Reviews, 67, 101265. doi: https://doi.org/10.1016/j.arr.2021.101265
Cilar Budler, L., & Budler, M. (2022). Physical activity during pregnancy: a systematic review for the assessment of current evidence with future recommendations. BMC Sports Science, Medicine and Rehabilitation, 14(1), 133. doi: https://doi.org/10.1186/s13102-022-00524-z
Cirulli, F., De Simone, R., Musillo, C., Ajmone-Cat, M. A., & Berry, A. (2022). Inflammatory Signatures of Maternal Obesity as Risk Factors for Neurodevelopmental Disorders: Role of Maternal Microbiota and Nutritional Intervention Strategies. Nutrients, 14(15). doi: https://doi.org/10.3390/nu14153150
Dennis, A. T., Salman, M., Paxton, E., Flint, M., Leeton, L., Roodt, F., . . . Dyer, R. A. (2019). Resting Hemodynamics and Response to Exercise Using the 6-Minute Walk Test in Late Pregnancy: An International Prospective Multicentre Study. Anesth Analg, 129(2), 450-457. doi: https://doi.org/10.1213/ane.0000000000003818
Djurovic, S., Schjetlein, R., Wisløff, F., Haugen, G., Husby, H., & Berg, K. (1997). Plasma concentrations of Lp(a) lipoprotein and TGF-beta1 are altered in preeclampsia. Clin Genet, 52(5), 371-376. doi: https://doi.org/10.1111/j.1399-0004.1997.tb04356.x
Gascoigne, E. L., Webster, C. M., Honart, A. W., Wang, P., Smith-Ryan, A., & Manuck, T. A. (2023). Physical activity and pregnancy outcomes: an expert review. Am J Obstet Gynecol MFM, 5(1), 100758. doi: https://doi.org/10.1016/j.ajogmf.2022.100758
Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S., & Nimmo, M. A. (2011). The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol, 11(9), 607-615. doi: https://doi.org/10.1038/nri3041
González-Gil, E. M., Santaliestra-Pasías, A. M., Buck, C., Gracia-Marco, L., Lauria, F., Pala, V., . . . Moreno, L. A. (2022). Improving cardiorespiratory fitness protects against inflammation in children: the IDEFICS study. Pediatric Research, 91(3), 681-689. doi: https://doi.org/10.1038/s41390-021-01471-0
Guinhouya, B. C., Duclos, M., Enea, C., & Storme, L. (2022). Beneficial Effects of Maternal Physical Activity during Pregnancy on Fetal, Newborn, and Child Health: Guidelines for Interventions during the Perinatal Period from the French National College of Midwives. J Midwifery Womens Health, 67 Suppl 1(Suppl 1), S149-s157. doi: https://doi.org/10.1111/jmwh.13424
Hauguel-de Mouzon, S., & Guerre-Millo, M. (2006). The placenta cytokine network and inflammatory signals. Placenta, 27(8), 794-798. doi: https://doi.org/10.1016/j.placenta.2005.08.009
Hekmatikar, A. H. A., Shamsi, M. M., Ashkazari, Z. S. Z., & Suzuki, K. (2021). Exercise in an Overweight Patient with Covid-19: A Case Study. Int J Environ Res Public Health, 18(11). doi: https://doi.org/10.3390/ijerph18115882
Kubler, J. M., Clifton, V. L., Moholdt, T., & Beetham, K. S. (2022). The effects of exercise during pregnancy on placental composition: A systematic review and meta-analysis. Placenta, 117, 39-46. doi:10.1016/j.placenta.2021.10.008
Lawrence, S. M., Ruoss, J. L., & Wynn, J. L. (2018). IL-17 in neonatal health and disease. Am J Reprod Immunol, 79(5), e12800. doi: https://doi.org/10.1111/aji.12800
Li, Y., Chen, J., Lin, Y., Xu, L., Sang, Y., Li, D., & Du, M. (2021). Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models. Front Immunol, 12, 694077. doi: https://doi.org/10.3389/fimmu.2021.694077
Mahdieh, M. S., Maryam, J., Bita, B., Neda, F., Motahare, M., Mahboobeh, B., . . . Kalani Behrooz, S. (2023). A pilot study on the relationship between Lactobacillus, Bifidibactrium counts and inflammatory factors following exercise training. Arch Physiol Biochem, 129(3), 778-787. doi: https://doi.org/10.1080/13813455.2021.1871763
Mokhtarzade, M., Molanouri Shamsi, M., Abolhasani, M., Bakhshi, B., Sahraian, M. A., Quinn, L. S., & Negaresh, R. (2021). Home-based exercise training influences gut bacterial levels in multiple sclerosis. Complementary Therapies in Clinical Practice, 45, 101463. doi: https://doi.org/10.1016/j.ctcp.2021.101463
Mor, G., Cardenas, I., Abrahams, V., & Guller, S. (2011). Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci, 1221(1), 80-87. doi: https://doi.org/10.1111/j.17496632.2010.05938.x
Moroishi, Y., Salas, L. A., Zhou, J., Baker, E. R., Hoen, A. G., Everson, T. M., . . . Karagas, M. R. (2023). Umbilical cord blood immune cell profiles in relation to the infant gut microbiome. iScience, 26(1). doi: https://doi.org/10.1016/j.isci.2022.105833
Muy-Rivera, M., Sanchez, S. E., Vadachkoria, S., Qiu, C., Bazul, V., & Williams, M. A. (2004). Transforming growth factor-beta1 (TGF-beta1) in plasma is associated with preeclampsia risk in Peruvian women with systemic inflammation. Am J Hypertens, 17(4), 334-338. doi: https://doi.org/10.1016/j.amjhyper.2003.12.010
Osborne, L. M., Brar, A., & Klein, S. L. (2019). The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders. Brain Behav Immun, 76, 7-16. doi: https://doi.org/10.1016/j.bbi.2018.11.015
Physical Activity and Exercise During Pregnancy and the Postpartum Period: ACOG Committee Opinion, Number 804. (2020). Obstet Gynecol, 135(4), e178-e188. doi: https://doi.org/10.1097/aog.0000000000003772
Pieren, D. K. J., Boer, M. C., & de Wit, J. (2022). The adaptive immune system in early life: The shift makes it count. Front Immunol, 13. doi: https://doi.org/10.3389/fimmu.2022.1031924
Ross, R., Dagnone, D., Jones, P. J., Smith, H., Paddags, A., Hudson, R., & Janssen, I. (2000). Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med, 133(2), 92-103. doi: https://doi.org/10.7326/0003-4819-133-2-200007180-00008
Saito, S., Tsuda, S., & Nakashima, A. (2023). T cell immunity and the etiology and pathogenesis of preeclampsia. Journal of Reproductive Immunology, 159, 104125. doi: https://doi.org/10.1016/j.jri.2023.104125
Sanjabi, S., Oh, S. A., & Li, M. O. (2017). Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection. Cold Spring Harb Perspect Biol, 9(6). doi: https://doi.org/10.1101/cshperspect.a022236
Santos, S., Voerman, E., Amiano, P., Barros, H., Beilin, L. J., Bergström, A., . . . Jaddoe, V. (2019). Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts. Bjog, 126(8), 984-995. doi: https://doi.org/10.1111/1471-0528.15661
Shin, D., & Song, W. O. (2015). Prepregnancy body mass index is an independent risk factor for gestational hypertension, gestational diabetes, preterm labor, and small- and large-for-gestational-age infants. The Journal of Maternal-Fetal & Neonatal Medicine, 28(14), 1679-1686. doi: https://doi.org/10.3109/14767058.2014.964675
Spence, T., Allsopp, P. J., Yeates, A. J., Mulhern, M. S., Strain, J. J., & McSorley, E. M. (2021). Maternal Serum Cytokine Concentrations in Healthy Pregnancy and Preeclampsia. J Pregnancy, 2021, 6649608. doi: https://doi.org/10.1155/2021/6649608
Tang, C., & Hu, W. (2023). The role of Th17 and Treg cells in normal pregnancy and unexplained recurrent spontaneous abortion (URSA): New insights into immune mechanisms. Placenta, 142, 18-26. doi: https://doi.org/10.1016/j.placenta.2023.08.065
Topper, J. N. (2000). TGF-beta in the cardiovascular system: molecular mechanisms of a context-specific growth factor. Trends Cardiovasc Med, 10(3), 132-137. doi: https://doi.org/10.1016/s1050-1738(00)00061-x
Witvrouwen, I., Mannaerts, D., Van Berendoncks, A. M., Jacquemyn, Y., & Van Craenenbroeck, E. M. (2020). The Effect of Exercise Training During Pregnancy to Improve Maternal Vascular Health: Focus on Gestational Hypertensive Disorders. Front Physiol, 11, 450. doi: https://doi.org/10.3389/fphys.2020.00450
Zhang, J.-W., Guan, J.-Q., & Zhong, Y.-X. (2023). Association of prenatal obesity and cord blood cytokine levels with allergic diseases in children: A 10-year follow-up cohort study. Heliyon, 9(6), e17375. doi: https://doi.org/10.1016/j.heliyon.2023.e17375
 
Journal of Exercise & Organ Cross Talk
Volume 4, Issue 4
Autumn 2024
Pages 274-283

  • Receive Date 08 October 2024
  • Revise Date 12 December 2024
  • Accept Date 13 December 2024

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