Exercise during Pregnancy: Developmental Programming Effects and Future Directions in Humans

Abstract

Epidemiological studies show that low birth weight is associated with mortality from cardiovascular disease in adulthood, indicating that chronic diseases could be influenced by hormonal or metabolic insults encountered in utero. This concept, now known as the Developmental Origins of Health and Disease hypothesis, postulates that the intrauterine environment may alter the structure and function of the organs of the fetus as well as the expression of genes that impart an increased vulnerability to chronic diseases later in life. Lifestyle interventions initiated during the prenatal period are crucial as there is the potential to attenuate progression towards chronic diseases. However, how lifestyle interventions such as physical activity directly affect human offspring metabolism and the potential mechanisms involved in regulating metabolic balance at the cellular level are not known. The purpose of this review is to highlight the effects of exercise during pregnancy on offspring metabolic health and emphasize gaps in the current human literature and suggestions for future research.

Key words

developmental programming - exercise - pregnancy - mitochondria

Publication History

Received: 15 October 2020

Accepted: 27 May 2021

Article published online:
03 August 2021

• References

• 1 Guh DP, Zhang W, Bansback N. et al. The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health 2009; 9: 88 doi:10.1186/1471-2458-9-88
• 2 Nishijima H, Satake K, Igarashi K. et al. Effects of exercise in overweight Japanese with multiple cardiovascular risk factors. Med Sci Sports Exerc 2007; 39: 926-933. doi:10.1249/mss.0b013e3180383d84
• 3 Donnelly JE, Honas JJ, Smith BK. et al. Aerobic exercise alone results in clinically significant weight loss for men and women: Midwest exercise trial 2. Obesity (Silver Spring) 2013; 21: E219-E228 doi:10.1002/oby.20145
• 4 Irwin ML, Yasui Y, Ulrich CM. et al. Effect of Exercise on total and intra-abdominal body fat in postmenopausal women. JAMA 2003; 289: 323-330 doi:10.1001/jama.289.3.323
• 5 Blumenthal JA, Sherwood A, Gullette ECD. et al. Exercise and weight loss reduce blood pressure in men and women with mild hypertension. Arch Intern Med 2000; 160: 1947-1958
• 6 Hellènius M-L, Faire Ud, Berglund B. et al. Diet and exercise are equally effective in reducing risk for cardiovascular disease. Results of a randomized controlled study in men with slightly to mederately raised cardiovascular risk factors. Atherosclerosis 1993; 103: 81-91
• 7 Posner JD, Gorman KM, Windsor-Landsberg L. et al. Low to moderate intensity endurance training in healthy older adults: Physiological responses after four months. J Am Geriatr Soc 1992; 40: 1-7
• 8 Bonanno JA, Lies JE. Effects of physical training on coronary risk factors. Am J Cardiol 1974; 33: 760-764
• 9 DiPietro L, Seeman TE, Stachenfeld NS. et al. Moderate-intensity aerobic training improves glucose tolerance in aging independent of abdominal adiposity. J Am Geriatr Soc 1998; 46: 875-879
• 10 Chang SH, Kim K, Lee J. et al. The effectiveness of physical activity interventions for low-income and ethnic minority children and youths: A meta-analysis. J Phys Act Health 2019; 16: 799-808 doi:10.1123/jpah.2018-0648
• 11 Jenum AK, Anderssen SA, Birkeland KI. et al. Promoting physical activity in a low-income multiethnic district: effects of a community intervention study to reduce risk factors for type 2 diabetes and cardiovascular disease: a community intervention reducing inactivity. Diabetes Care 2006; 29: 1605-1612 doi:10.2337/dc05-1587
• 12 [Anonym]. Physical activity and exercise during pregnancy and the postpartum period: ACOG committee opinion, number 804. Obstet Gynecol 2020; 135: e178-e188 doi:10.1097/aog.0000000000003772
• 13 Barker DJ, Winter PD, Osmond C. et al. Weight in infancy and death from ischaemic heart disease. Lancet 1989; 2: 577-580 doi:10.1016/s0140-6736(89)90710-1
• 14 Bentov Y, Yavorska T, Esfandiari N. et al. The contribution of mitochondrial function to reproductive aging. J Assist Reprod Genet 2011; 28: 773-783 doi:10.1007/s10815-011-9588-7
• 15 Catalano PM, Shankar K. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ 2017; 356: j1 doi:10.1136/bmj.j1
• 16 Phelan S. Pregnancy: a "teachable moment" for weight control and obesity prevention. Am J Obstet Gynecol 2010; 202: 135 e131-e138 doi:10.1016/j.ajog.2009.06.008
• 17 Wolfe LA, Weissgerber TL. Clinical physiology of exercise in pregnancy: A literature review. J Obstet Gynaecol Can 2003; 25: 473-483 doi:10.1016/s1701-2163(16)30309-7
• 18 Barakat R, Perales M. Resistance exercise in pregnancy and outcome. Clin Obstet Gynecol 2016; 59: 591-599
• 19 Piercy KL, Troiano RP, Ballard RM. et al. The physical activity guidelines for Americans. JAMA 2018; 320: 2020-2028 doi:10.1001/jama.2018.14854
• 20 Garber CE, Blissmer B, Deschenes MR. et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: Guidance for prescribing exercise. Med Sci Sports Exerc 2011; 43: 1334-1359 doi:10.1249/MSS.0b013e318213fefb
• 21 de Oliveria Melo AS, Silva JL, Tavares JS. et al. Effect of a physical exercise program during pregnancy on uteroplacental and fetal blood flow and fetal growth: A randomized controlled trial. Obstet Gynecol 2012; 120: 302-310 doi:10.1097/AOG.0b013e31825de592
• 22 Price BB, Amini SB, Kappeler K. Exercise in pregnancy: effect on fitness and obstetric outcomes-a randomized trial. Med Sci Sports Exerc 2012; 44: 2263-2269 doi:10.1249/MSS.0b013e318267ad67
• 23 Owe KM, Nystad W, Skjaerven R. et al. Exercise during pregnancy and the gestational age distribution: a cohort study. Med Sci Sports Exerc 2012; 44: 1067-1074 doi:10.1249/MSS.0b013e3182442fc9
• 24 Barakat R, Pelaez M, Montejo R. et al. Exercise throughout pregnancy does not cause preterm delivery: A randomized, controlled trial. J Phys Act Health 2014; 11: 1012-1017 doi:10.1123/jpah.2012-0344
• 25 Zhang J, Savitz DA. Exercise during pregnancy among US women. Ann Epidemiol 1996; 6: 53-59 doi:10.1016/1047-2797(95)00093-3
• 26 Nascimento SL, Surita FG, Godoy AC. et al. Physical activity patterns and factors related to exercise during pregnancy: A cross sectional study. PLoS One 2015; 10: e0128953 doi:10.1371/journal.pone.0128953
• 27 Evenson KR, Savitz DA, Huston SL. Leisure-time physical activity among pregnant women in the US. Paediatr Perinat Epidemiol 2004; 18: 400-407
• 28 Walsh JM, McGowan C, Byrne J. et al. Prevalence of physical activity among healthy pregnant women in Ireland. Int J Gynaecol Obstet 2011; 114: 154-155 doi:10.1016/j.ijgo.2011.02.016
• 29 Hegaard HK, Damm P, Hedegaard M. et al. Sports and leisure time physical activity during pregnancy in nulliparous women. Matern Child Health J 2011; 15: 806-813 doi:10.1007/s10995-010-0647-y
• 30 Liu J, Blair SN, Teng Y. et al. Physical activity during pregnancy in a prospective cohort of British women: results from the Avon longitudinal study of parents and children. Eur J Epidemiol 2011; 26: 237-247 doi:10.1007/s10654-010-9538-1
• 31 Domingues MR, Barros AJD. Leisure-time physical activity during pregnancy in the 2004 Pelotas Birth Cohort Study. Rev Saude Publica 2007; 41: 173-180
• 32 Nascimento SL, Surita FG, Cecatti JG. Physical exercise during pregnancy: a systematic review. Curr Opin Obstet Gynecol 2012; 24: 387-394 doi:10.1097/GCO.0b013e328359f131
• 33 Callaway LK, Colditz PB, Byrne NM. et al. Prevention of gestational diabetes: feasibility issues for an exercise intervention in obese pregnant women. Diabetes Care 2010; 33: 1457-1459 doi:10.2337/dc09-2336
• 34 Peaceman AM, Clifton RG, Phelan S. et al. Lifestyle interventions limit gestational weight gain in women with overweight or obesity: LIFE-Moms prospective meta-analysis. Obesity (Silver Spring) 2018; 26: 1396-1404 doi:10.1002/oby.22250
• 35 Redman LM, Drews KL, Klein S. et al. Attenuated early pregnancy weight gain by prenatal lifestyle interventions does not prevent gestational diabetes in the LIFE-Moms consortium. Diabetes Res Clin Pract 2021; 171: 108549 doi:10.1016/j.diabres.2020.108549
• 36 May LE, Knowlton J, Hanson J. et al. Effects of exercise during pregnancy on maternal heart rate and heart rate variability. PM R 2016; 8: 611-617 doi:10.1016/j.pmrj.2015.11.006
• 37 Martin CL, Brunner Huber LR. Physical activity and hypertensive complications during pregnancy: Findings from 2004 to 2006 north carolina pregnancy risk assessment monitoring system. Birth 2010; 37: 202-210 doi:10.1111/j.1523-536x.2010.00407.x
• 38 Kawabata I, Nakai A, Sekiguchi A. et al. The effect of regular exercise training during pregnancy on postpartum brachial-ankle pulse wave velocity, a measure of arterial stiffness. J Sports Sci Med 2012; 11: 489-494
• 39 Haakstad LAH, Edvardsen E, Bø K. Effect of regular exercise on blood pressure in normotensive pregnant women. A randomized controlled trial. Hypertens Pregnancy 2016; 35: 170-180 doi:10.3109/10641955.2015.1122036
• 40 Barakat R, Pelaez M, Cordero Y. et al. Exercise during pregnancy protects against hypertension and macrosomia: randomized clinical trial. Am J Obstet Gynecol 2016; 214: 649.e1-649.e8 doi:10.1016/j.ajog.2015.11.039
• 41 May LE, Allen JJ, Gustafson KM. Fetal and maternal cardiac responses to physical activity and exercise during pregnancy. Early Hum Dev 2016; 94: 49-52 doi:10.1016/j.earlhumdev.2016.01.005
• 42 Mottola MF, Artal R. Fetal and maternal metabolic responses to exercise during pregnancy. Early Hum Dev 2016; 94: 33-41 doi:10.1016/j.earlhumdev.2016.01.008
• 43 Newton ER, May L. Adaptation of maternal-fetal physiology to exercise in pregnancy: The basis of guidelines for physical activity in pregnancy. Clin Med Insights Womens Health 2017; 10: 1179562X17693224 doi:10.1177/1179562X17693224
• 44 Hytten F, Chamberlain G. Clinical Physiology in Obstetrics. Oxford: Blackwell Scientific Publications; 1991
• 45 Gabbe S, Neibyl J, Simpson J. Obstetrics: Normal and Problem Pregnancies. 2nd ed. New York: Churchill Livingstone; 1991
• 46 Mottola MF, Davenport MH, Brun CR. et al. VO2peak prediction and exercise prescription for pregnant women. Med Sci Sports Exerc 2006; 38: 1389-1395 doi:10.1249/01.mss.0000228940.09411.9c
• 47 Khodiguian N, Jaque-Fortunato SV, Wiswell RA. et al. A comparison of cross-sectional and longitudinal methods of assessing the influence of pregnancy on cardiac function during exercise. Semin Perinatol 1996; 20: 232-241
• 48 Clapp JF. The effects of maternal exercise on fetal oxygenation and feto-placental growth. Eur J Obstet Gynecol Reprod Biol 2003; 110: S80-S85 doi:10.1016/s0301-2115(03)00176-3
• 49 Clapp JF. Maternal carbohydrate intake and pregnancy outcome. Proc Nutr Soc 2002; 61: 45-50 doi:10.1079/pns2001129
• 50 Reyes LM, Davenport MH. Exercise as a therapeutic intervention to optimize fetal weight. Pharmacol Res 2018; 132: 160-167 doi:10.1016/j.phrs.2018.04.016
• 51 Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev 1974; 54: 75-159
• 52 Jones MT, Norton KI, Dengel DR. et al. Effects of training on reproductive tissue blood flow in exercising pregnant rats. J Appl Physiol (1985) 1990; 69: 2097-2103
• 53 Pivarnik JM, Mauer MB, Ayres NA. et al. Effects of chronic exercise on blood volume expansion and hematologic indices during pregnancy. Obstet Gynecol 1994; 83: 265-269
• 54 Szymanski LM, Satin AJ. Strenuous exercise during pregnancy: is there a limit?. Am J Obstet Gynecol 2012; 207: 179 e171-e176 doi:10.1016/j.ajog.2012.07.021
• 55 Brett KE, Ferraro ZM, Holcik M. et al. Prenatal physical activity and diet composition affect the expression of nutrient transporters and mTOR signaling molecules in the human placenta. Placenta 2015; 36: 204-212 doi:10.1016/j.placenta.2014.11.015
• 56 Hutchinson KA, Vuong NH, Mohammad S. et al. Physical activity during pregnancy is associated with increased placental FATP4 protein expression. Reprod Sci 2020; 27: 1909-1919 doi:10.1007/s43032-020-00210-w
• 57 Ramirez-Velez R, Bustamante J, Czerniczyniec A. et al. Effect of exercise training on eNOS expression, NO production and oxygen metabolism in human placenta. PLoS One 2013; 8: e80225 doi:10.1371/journal.pone.0080225
• 58 Day PE, Ntani G, Crozier SR. et al. Maternal factors are associated with the expression of placental genes involved in amino acid metabolism and transport. PLoS One 2015; 10: e0143653 doi:10.1371/journal.pone.0143653
• 59 Son JS, Liu X, Tian Q. et al. Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth. J Physiol 2019; 597: 3333-3347 doi:10.1113/jp277698
• 60 Song L, Yan J, Wang N. et al. Prenatal exercise reverses high-fat-diet-induced placental alterations and alters male fetal hypothalamus during late gestation in rats†. Biol Reprod 2019; 102: 705-716 doi:10.1093/biolre/ioz213
• 61 Mangwiro YTM, Cuffe JSM, Mahizir D. et al. Exercise initiated during pregnancy in rats born growth restricted alters placental mTOR and nutrient transporter expression. J Physiol 2019; 597: 1905-1918 doi:10.1113/jp277227
• 62 Baird J, Fisher D, Lucas P. et al. Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 2005; 331: 929 doi:10.1136/bmj.38586.411273.EO.
• 63 Boney CM, Verma A, Tucker R. et al. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005; 115: e290-e296 doi:10.1542/peds.2004-1808
• 64 Nordman H, Jääskeläinen J, Voutilainen R. Birth size as a determinant of cardiometabolic risk factors in children. Horm Res Paediatr 2020; 93: 144-153 doi:10.1159/000509932
• 65 Pettitt DJ, Jovanovic L. Birth weight as a predictor of type 2 diabetes mellitus: The U-shaped curve. Curr Diab Rep 2001; 1: 78-81 doi:10.1007/s11892-001-0014-x
• 66 Lumey LH, Khalangot MD, Vaiserman AM. Association between type 2 diabetes and prenatal exposure to the Ukraine famine of 1932-33: a retrospective cohort study. Lancet Diabetes Endocrinol 2015; 3: 787-794 doi:10.1016/s2213-8587(15)00279-x
• 67 Lahti-Pulkkinen M, Bhattacharya S, Wild SH. et al. Consequences of being overweight or obese during pregnancy on diabetes in the offspring: a record linkage study in Aberdeen, Scotland. Diabetologia 2019; 62: 1412-1419 doi:10.1007/s00125-019-4891-4
• 68 Kaar JL, Crume T, Brinton JT. et al. Maternal obesity, gestational weight gain, and offspring adiposity: The exploring perinatal outcomes among children study. J Pediatr 2014; 165: 509-515 doi:10.1016/j.jpeds.2014.05.050
• 69 Jönsson J, Renault KM, García-Calzón S. et al. Lifestyle intervention in pregnant women with obesity impacts cord blood dna methylation which associates with body composition in the offspring. Diabetes 2021; 70: 854-866 doi:10.2337/db20-0487
• 70 Dahly DL, Li X, Smith HA. et al. Associations between maternal lifestyle factors and neonatal body composition in the Screening for Pregnancy Endpoints (Cork) cohort study. Int J Epidemiol 2018; 47: 131-145 doi:10.1093/ije/dyx221
• 71 Mudd LM, Pivarnik J, Holzman CB. et al. Leisure-time physical activity in pregnancy and the birth weight distribution: Where is the effect?. J Phys Act Health 2012; 9: 1168-1177
• 72 Ferrari N, Bae-Gartz I, Bauer C. et al. Exercise during pregnancy and its impact on mothers and offspring in humans and mice. J Dev Orig Health Dis 2018; 9: 63-76 doi:10.1017/S2040174417000617
• 73 Guillemette L, Hay JL, Kehler DS. et al. Exercise in pregnancy and children's cardiometabolic risk factors: A systematic review and meta-analysis. Sports Med Open 2018; 4: 35 doi:10.1186/s40798-018-0148-x
• 74 Clapp JF. Influence of endurance exercise and diet on human placental development and fetal growth. Placenta 2006; 27: 527-534 doi:10.1016/j.placenta.2005.07.010
• 75 Clapp JF, Capeless EL. Neonatal morphometrics after endurance exercise during pregnancy. Am J Obstet Gynecol 1990; 163: 1805-1811 doi:10.1016/0002-9378(90)90754-u
• 76 Bisson M, Lavoie-Guénette J, Tremblay A. et al. Physical activity volumes during pregnancy: A systematic review and meta-analysis of observational studies assessing the association with infant's birth weight. 2016; 06: e170-e197 doi:10.1055/s-0036-1583169
• 77 Hegaard HK, Pedersen BK, Nielsen BB. et al. Leisure time physical activity during pregnancy and impact on gestational diabetes mellitus, pre-eclampsia, preterm delivery and birth weight: a review. Acta Obstet Gynecol Scand 2007; 86: 1290-1296 doi:10.1080/00016340701647341
• 78 Owe KM, Nystad W, Bø K. Association between regular exercise and excessive newborn birth weight. Obstet Gynecol 2009; 114: 770-776 doi:10.1097/AOG.0b013e3181b6c105
• 79 Alderman BW, Zhao H, Holt VL. et al. Maternal physical activity in pregnancy and infant size for gestational age. Ann Epidemiol 1998; 8: 513-519
• 80 Juhl M, Olsen J, Andersen PK. et al. Physical exercise during pregnancy and fetal growth measures: A study within the Danish National Birth Cohort. Am J Obstet Gynecol 2010; 202: 63.e1-8 doi:10.1016/j.ajog.2009.07.033
• 81 Clapp JF. Long-term outcome after exercising throughout pregnancy: fitness and cardiovascular risk. Am J Obstet Gynecol 2008; 199: 489 e481-e486 doi:10.1016/j.ajog.2008.05.006
• 82 Davenport MH, Sobierajski F, Mottola MF. et al. Glucose responses to acute and chronic exercise during pregnancy: A systematic review and meta-analysis. Br J Sports Med 2018; 52: 1357-1366 doi:10.1136/bjsports-2018-099829
• 83 Quiclet C, Dubouchaud H, Berthon P. et al. Maternal exercise modifies body composition and energy substrates handling in male offspring fed a high-fat/high-sucrose diet. J Physiol 2017; 595: 7049-7062
• 84 Carter LG, Lewis KN, Wilkerson DC. et al. Perinatal exercise improves glucose homeostasis in adult offspring. Am J Physiol Endocrinol Metab 2012; 303: E1061-E1068 doi:10.1152/ajpendo.00213.2012
• 85 Blaize AN, Breslin E, Donkin SS. et al. Maternal exercise does not significantly alter adult rat offspring vascular function. Med Sci Sports Exerc 2015; 47: 2340-2346 doi:10.1249/mss.0000000000000665
• 86 Fick A. Ueber die Messung des Blutquantum in den Herzventrikeln. Sb Phys Med Ges Worzburg 1870; 16-17
• 87 Son JS, Chae SA, Wang H. et al. Maternal inactivity programs skeletal muscle dysfunction in offspring mice by attenuating apelin signaling and mitochondrial biogenesis. Cell Rep 2020; 33: 108461
• 88 Eclarinal JD, Zhu S, Baker MS. et al. Maternal exercise during pregnancy promotes physical activity in adult offspring. FASEB J 2016; 30: 2541-2548
• 89 Wilmore JH, Stanforth PR, Gagnon J. et al. Cardiac output and stroke volume changes with endurance training: The HERITAGE Family Study. Med Sci Sports Exerc 2001; 33: 99-106
• 90 Hambrecht R, Gielen S, Linke A. et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial. JAMA 2000; 283: 3095-3101
• 91 Carter JB, Banister EW, Blaber AP. Effect of endurance exercise on autonomic control of heart rate. Sports Med 2003; 33: 33-46
• 92 Martinmäki K, Häkkinen K, Mikkola J. et al. Effect of low-dose endurance training on heart rate variability at rest and during an incremental maximal exercise test. Eur J Appl Physiol 2008; 104: 541-548
• 93 Uusitalo AL, Laitinen T, Väisänen SB. et al. Effects of endurance training on heart rate and blood pressure variability. Clin Physiol Funct Imaging 2002; 22: 173-179
• 94 Harris JE, Pinckard KM, Wright KR. et al. Exercise-induced 3′-sialyllactose in breast milk is a critical mediator to improve metabolic health and cardiac function in mouse offspring. Nat Metab 2020; 2: 678-687
• 95 Beeson JH, Blackmore HL, Carr SK. et al. Maternal exercise intervention in obese pregnancy improves the cardiovascular health of the adult male offspring. Mol Metab 2018; 16: 35-44
• 96 Chung E, Joiner HE, Skelton T. et al. Maternal exercise upregulates mitochondrial gene expression and increases enzyme activity of fetal mouse hearts. Physiol Rep 2017; 5: e13184
• 97 Currie KD, Thomas SG, Goodman JM. Effects of short-term endurance exercise training on vascular function in young males. Eur J Appl Physiol 2009; 107: 211-218
• 98 Sugawara J, Komine H, Hayashi K. et al. Reduction in α-adrenergic receptor-mediated vascular tone contributes to improved arterial compliance with endurance training. Int J Cardiol 2009; 135: 346-352
• 99 Hernandez JP, Franke WD. Effects of a 6-mo endurance-training program on venous compliance and maximal lower body negative pressure in older men and women. J Appl Physiol (1985) 2005; 99: 1070-1077
• 100 Newcomer S, Taheripour P, Bahls M. et al. Impact of porcine maternal aerobic exercise training during pregnancy on endothelial cell function of offspring at birth. J Dev Orig Health Dis 2012; 3: 04-09
• 101 Bahls M, Sheldon RD, Taheripour P. et al. Mother's exercise during pregnancy programmes vasomotor function in adult offspring. Exp Physiol 2014; 99: 205-219
• 102 Blaize N, Zartman E, Biel T. et al. Impact of maternal exercise during pregnancy on arteiral function and atherosclerosis formation in swine offspring fed a high fat diet. Enliven: Gynecol Obestet 2015; 1: 005-015
• 103 Blaize AN, Breslin E, Donkin SS. et al. Maternal exercise does not significantly alter adult rat offspring vascular function. Med Sci Sports Exerc 2015; 47: 2340-2346
• 104 Boonpattrawong NP, Golbidi S, Tai DC. et al. Exercise during pregnancy mitigates the adverse effects of maternal obesity on adult male offspring vascular function and alters one-carbon metabolism. Physiol Rep 2020; 8: e14582
• 105 Li S, Chen Y, Zhang Y. et al. Exercise during pregnancy enhances vascular function via epigenetic repression of CaV1. 2 channel in offspring of hypertensive rats. Life Sci 2019; 231: 116576
• 106 Brislane Á, Jones H, Holder SM. et al. The effect of exercise during pregnancy on maternal and offspring vascular outcomes: A pilot study. Reprod Sci 2020; 1-14
• 107 May LE, Glaros A, Yeh H-W. et al. Aerobic exercise during pregnancy influences fetal cardiac autonomic control of heart rate and heart rate variability. Early Hum Dev 2010; 86: 213-217
• 108 May LE, Scholtz SA, Suminski R. et al. Aerobic exercise during pregnancy influences infant heart rate variability at one month of age. Early Hum Dev 2014; 90: 33-38
• 109 Ingjer F. Capillary supply and mitochondrial content of different skeletal muscle fiber types in untrained and endurance-trained men. A histochemical and ultrastructural study. Eur J Appl Physiol Occup Physiol 1979; 40: 197-209
• 110 Fritzen AM, Andersen SP, Qadri KAN. et al. Effect of aerobic exercise training and deconditioning on oxidative capacity and muscle mitochondrial enzyme machinery in young and elderly individuals. J Clin Med 2020; 9: 3113
• 111 Ingjer F. Effects of endurance training on muscle fibre ATP-ase activity, capillary supply and mitochondrial content in man. J Physiol 1979; 294: 419-432
• 112 Liu J, Lee I, Feng H-Z. et al. Aerobic exercise preconception and during pregnancy enhances oxidative capacity in the hindlimb muscles of mice offspring. J Strength Cond Res 2018; 32: 1391-1403
• 113 Siti F, Dubouchaud H, Hininger I. et al. Maternal exercise before and during gestation modifies liver and muscle mitochondria in rat offspring. J Exp Biol 2019; 222: jeb194969
• 114 Spiegelman BM. Transcriptional control of mitochondrial energy metabolism through the PGC1 coactivators. Novartis Found Symp 2007; 287: 60-63
• 115 Laker RC, Lillard TS, Okutsu M. et al. Exercise prevents maternal high-fat diet–induced hypermethylation of the Pgc-1α gene and age-dependent metabolic dysfunction in the offspring. Diabetes 2014; 63: 1605-1611
• 116 Huang T-Y, Zheng D, Houmard JA. et al. Overexpression of PGC-1α increases peroxisomal biogenesis and mitochondrial lipid oxidation in human primary myotubes. FASEB J 2016; 30: 1246.1243-1246.1243
• 117 Geng T, Li P, Okutsu M. et al. PGC-1α plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. Am J Physiol Cell Physiol 2010; 298: C572-C579
• 118 Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 2014; 371: 1131-1141 doi:10.1056/NEJMra1011035
• 119 Saben J, Lindsey F, Zhong Y. et al. Maternal obesity is associated with a lipotoxic placental environment. Placenta 2014; 35: 171-177 doi:10.1016/j.placenta.2014.01.003
• 120 Raipuria M, Bahari H, Morris MJ. Effects of maternal diet and exercise during pregnancy on glucose metabolism in skeletal muscle and fat of weanling rats. PLoS One 2015; 10: e0120980
• 121 Stanford KI, Lee M-Y, Getchell KM. et al. Exercise before and during pregnancy prevents the deleterious effects of maternal high-fat feeding on metabolic health of male offspring. Diabetes 2015; 64: 427-433
• 122 Kasch J, Kanzleiter I, Saussenthaler S. et al. Insulin sensitivity linked skeletal muscle Nr4a1 DNA methylation is programmed by the maternal diet and modulated by voluntary exercise in mice. J Nutr Biochem 2018; 57: 86-92
• 123 Stanford KI, Takahashi H, So K. et al. Maternal exercise improves glucose tolerance in female offspring. Diabetes 2017; 66: 2124-2136
• 124 Vega CC, Reyes-Castro LA, Bautista CJ. et al. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism. Int J Obes (Lond) 2015; 39: 712-719
• 125 Zhou L, Xiao X, Li M. et al. Maternal exercise improves high-fat diet-induced metabolic abnormalities and gut microbiota profiles in mouse dams and offspring. Front Cell Infect Microbiol 2020; 10: 292
• 126 DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 2009; 32: S157-S163 doi:10.2337/dc09-S302
• 127 Carter LG, Qi NR, De Cabo R. et al. Maternal exercise improves insulin sensitivity in mature rat offspring. Med Sci Sports Exerc 2013; 45: 832-840
• 128 Dabelea D, Mayer-Davis EJ, Lamichhane AP. et al. Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case-Control Study. Diabetes care 2008; 31: 1422-1426
• 129 Zambrano E, Sosa-Larios T, Calzada L. et al. Decreased basal insulin secretion from pancreatic islets of pups in a rat model of maternal obesity. J Endocrinol 2016; 231: 49-57
• 130 Nicholas LM, Nagao M, Kusinski LC. et al. Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice. Diabetologia 2020; 63: 324-337
• 131 Han J, Xu J, Epstein P. et al. Long-term effect of maternal obesity on pancreatic beta cells of offspring: reduced beta cell adaptation to high glucose and high-fat diet challenges in adult female mouse offspring. Diabetologia 2005; 48: 1810-1818
• 132 Zheng J, Alves-Wagner AB, Stanford KI. et al. Maternal and paternal exercise regulate offspring metabolic health and beta cell phenotype. BMJ Open Diabetes Res Care 2020; 8: e000890
• 133 Gorgens SW, Eckardt K, Jensen J. et al. Exercise and regulation of adipokine and myokine production. Prog Mol Biol Transl Sci 2015; 135: 313-336 doi:10.1016/bs.pmbts.2015.07.002
• 134 Keller P, Keller C, Carey AL. et al. Interleukin-6 production by contracting human skeletal muscle: Autocrine regulation by IL-6. Biochem Biophys Res Commun 2003; 310: 550-554 doi:10.1016/j.bbrc.2003.09.048
• 135 Cuppini R, Sartini S, Agostini D. et al. BDNF expression in rat skeletal muscle after acute or repeated exercise. Arch Ital Biol 2007; 145: 99-110
• 136 Nielsen AR, Mounier R, Plomgaard P. et al. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. J Physiol 2007; 584: 305-312 doi:10.1113/jphysiol.2007.139618
• 137 Pedersen BK, Akerstrom TC, Nielsen AR. et al. Role of myokines in exercise and metabolism. J Appl Physiol (1985) 2007; 103: 1093-1098 doi:10.1152/japplphysiol.00080.2007
• 138 Ogborn DI, Gardiner PF. Effects of exercise and muscle type on BDNF, NT-4/5, and TrKB expression in skeletal muscle. Muscle Nerve 2010; 41: 385-391 doi:10.1002/mus.21503
• 139 Tamura Y, Watanabe K, Kantani T. et al. Upregulation of circulating IL-15 by treadmill running in healthy individuals: Is IL-15 an endocrine mediator of the beneficial effects of endurance exercise?. Endocr J 2011; 58: 211-215
• 140 Wolsk E, Mygind H, Grondahl TS. et al. IL-6 selectively stimulates fat metabolism in human skeletal muscle. Am J Physiol Endocrinol Metab 2010; 299: E832-E840 doi:10.1152/ajpendo.00328.2010
• 141 Wood J, Tse MCL, Yang X. et al. BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle. Metabolism 2018; 87: 113-122 doi:10.1016/j.metabol.2018.06.007
• 142 Yang X, Brobst D, Chan WS. et al. Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility. Sci Signal 2019; 12: eaau1468 doi:10.1126/scisignal.aau1468
• 143 Andersson S, Zomorodipour A, Andersson J. et al. The genome sequence of Rickettsia prowazekii and the origin of the mitochondria. Nature 1998; 396: 133-140
• 144 Calvo SE, Clauser KR, Mootha VK. MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins. Nucleic Acids Res 2016; 44: D1251-D1257 doi:10.1093/nar/gkv1003
• 145 Taanman J-W. The mitochondrial genome: Structure, transcription, translation and replication. Biochim Biophys Acta 1999; 1410: 103-123
• 146 Zou W, Slone J, Cao Y. et al. Mitochondria and their role in human reproduction. DNA Cell Biol 2020; 39: 1370-1378 doi:10.1089/dna.2019.4807
• 147 Luo S, Valencia CA, Zhang J. et al. Biparental inheritance of mitochondrial DNA in humans. Proc Natl Acad Sci USA 2018; 115: 13039-13044 doi:10.1073/pnas.1810946115
• 148 Ryan TE, Yamaguchi DJ, Schmidt CA. et al. Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants. JCI Insight 2018; 3: e123235 doi:10.1172/jci.insight.123235
• 149 Wu LL, Russell DL, Wong SL. et al. Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors. Development 2015; 142: 681-691 doi:10.1242/dev.114850
• 150 Boudoures AL, Saben J, Drury A. et al. Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. Dev Biol 2017; 426: 126-138 doi:10.1016/j.ydbio.2017.04.005
• 151 Witorsch RJ. Low-dose in utero effects of xenoestrogens in mice and their relevance to humans: An analytical review of the literature. Food Chem Toxicol 2002; 40: 905-912
• 152 Morales-Prieto DM, Chaiwangyen W, Ospina-Prieto S. et al. MicroRNA expression profiles of trophoblastic cells. Placenta 2012; 33: 725-734 doi:10.1016/j.placenta.2012.05.009
• 153 Soni C, Karande AA. Glycodelin A suppresses the cytolytic activity of CD8+ T lymphocytes. Mol Immunol 2010; 47: 2458-2466 doi:10.1016/j.molimm.2010.06.008
• 154 Springer SA, Diaz SL, Gagneux P. Parallel evolution of a self-signal: humans and new world monkeys independently lost the cell surface sugar Neu5Gc. Immunogenetics 2014; 66: 671-674 doi:10.1007/s00251-014-0795-0
• 155 Heden TD, Ryan TE, Ferrara PJ. et al. Greater oxidative capacity in primary myotubes from endurance-trained women. Med Sci Sports Exerc 2017; 49: 2151-2157 doi:10.1249/MSS.0000000000001352
• 156 McAinch AJ, Steinberg GR, Mollica J. et al. Differential regulation of adiponectin receptor gene expression by adiponectin and leptin in myotubes derived from obese and diabetic individuals. Obesity 2006; 14: 1898-1904
• 157 Zou K, Hinkley JM, Park S. et al. Altered tricarboxylic acid cycle flux in primary myotubes from severely obese humans. Int J Obes (Lond) 2019; 43: 895-905 doi:10.1038/s41366-018-0137-7
• 158 Park S, Turner KD, Zheng D. et al. Electrical pulse stimulation induces differential responses in insulin action in myotubes from severely obese individuals. J Physiol 2019; 597: 449-466 doi:10.1113/JP276990
• 159 Lund J, Helle SA, Li Y. et al. Higher lipid turnover and oxidation in cultured human myotubes from athletic versus sedentary young male subjects. Sci Rep 2018; 8: 17549 doi:10.1038/s41598-018-35715-7
• 160 Lund J, Rustan AC, Lovsletten NG. et al. Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism. PLoS One 2017; 12: e0175441 doi:10.1371/journal.pone.0175441
• 161 Bourlier V, Saint-Laurent C, Louche K. et al. Enhanced glucose metabolism is preserved in cultured primary myotubes from obese donors in response to exercise training. J Clin Endocrinol Metab 2013; 98: 3739-3747 doi:10.1210/jc.2013-1727
• 162 Pittenger MF, Mackay AM, Beck SC. et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147
• 163 Boyle KE, Patinkin ZW, Shapiro AL. et al. Mesenchymal stem cells from infants born to obese mothers exhibit greater potential for adipogenesis: The Healthy Start BabyBUMP Project. Diabetes 2016; 65: 647-659 doi:10.2337/db15-0849
• 164 Boyle KE, Patinkin ZW, Shapiro ALB. et al. Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants. Mol Metab 2017; 6: 1503-1516 doi:10.1016/j.molmet.2017.08.012
• 165 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817