Impact of Maternal Circadian Rhythm Disruption during Pregnancy on Cardiac Remodeling in Offspring: A Comprehensive Review

Zhang P

Zhang P

Volume6-Issue11
Dates: Received: 2025-11-06 | Accepted: 2025-11-12 | Published: 2025-11-13
Pages: 1691-1703

Abstract

Emerging evidence from both human and animal studies indicates that circadian rhythm disruption during critical developmental periods can have profound long-term consequences for cardiovascular health. This review synthesizes current knowledge on the impact of maternal circadian disturbance during pregnancy on cardiac remodeling in offspring, with particular emphasis on sex-specific effects and underlying molecular mechanisms. Drawing from recent experimental models, we explore how in utero circadian disruption predisposes offspring, especially males, to pathological cardiac remodeling, characterized by ventricular chamber dilatation, enhanced myocardial fibrosis, decreased contractility, and increased susceptibility to arrhythmias. However, emerging evidence also indicates that female offspring are not entirely spared, with risks potentially mediated through other pathways such as pregnancy complications. The review highlights the emerging role of sex-specific molecular pathways, including the secret globin gene, Scgb1a1, alongside other key mechanisms such as epigenetic regulators and inflammatory pathways, and discusses how circadian gene expression alterations in the heart contribute to these phenotypes. Understanding these relationships provides crucial insights into the developmental origins of cardiovascular disease and may inform future prevention strategies targeting circadian health during pregnancy.

FullText HTML FullText PDF DOI: 10.37871/jbres2222

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How to cite this article

Zhang P. Impact of Maternal Circadian Rhythm Disruption during Pregnancy on Cardiac Remodeling in Offspring: A Comprehensive Review. J Biomed Res Environ Sci. 2025 Nov 13; 6(11): 1691-1703. doi: 10.37871/jbres2222, Article ID: JBRES2222, Available at: https://www.jelsciences.com/articles/jbres2222.pdf

Subject area(s)

Biomedicine

Molecular Biology

Biology

References

Scheer FAJL, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4453-8. doi: 10.1073/pnas.0808180106. Epub 2009 Mar 2. PMID: 19255424; PMCID: PMC2657421.
Helfrich-Förster C, Bertolini E, Menegazzi P. Flies as models for circadian clock adaptation to environmental challenges. Eur J Neurosci. 2020 Jan;51(1):166-181. doi: 10.1111/ejn.14180. Epub 2018 Oct 22. PMID: 30269385; PMCID: PMC7027873.
Bertolini E, Schubert FK, Zanini D, Sehadová H, Helfrich-Förster C, Menegazzi P. Life at High Latitudes Does Not Require Circadian Behavioral Rhythmicity under Constant Darkness. Curr Biol. 2019 Nov 18;29(22):3928-3936.e3. doi: 10.1016/j.cub.2019.09.032. Epub 2019 Oct 31. PMID: 31679928.
Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 2012:35:445-62. doi: 10.1146/annurev-neuro-060909-153128. Epub 2012 Apr 5. PMID: 22483041; PMCID: PMC3710582.
Partch CL, Green CB, Takahashi JS. Molecular architecture of the mammalian circadian clock. Trends Cell Biol. 2014 Feb;24(2):90-9. doi: 10.1016/j.tcb.2013.07.002. Epub 2013 Aug 1. PMID: 23916625; PMCID: PMC3946763.
Golombek DA, Rosenstein RE. Physiology of circadian entrainment. Physiol Rev. 2010 Jul;90(3):1063-102. doi: 10.1152/physrev.00009.2009. PMID: 20664079.
Fagiani F, Marino DD, Romagnoli A, Travelli C, Voltan Davide, Mannelli LDC, Racchi M, Govoni S, Lanni C. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct Target Ther. 2022 Feb 8;7(1):41. doi: 10.1038/s41392-022-00899-y. PMID: 35136018; PMCID: PMC8825842.
Rabinovich-Nikitin I, Lieberman B, Martino TA, Kirshenbaum LA. Circadian-Regulated Cell Death in Cardiovascular Diseases. Circulation. 2019 Feb 12;139(7):965-980. doi: 10.1161/CIRCULATIONAHA.118.036550. PMID: 30742538.
Thakur A, Kishore R. Neurobiology of the circadian clock and its role in cardiovascular disease: Mechanisms, biomarkers, and chronotherapy. Neurobiol Sleep Circadian Rhythms. 2025 Jun 3:19:100131. doi: 10.1016/j.nbscr.2025.100131. eCollection 2025 Nov. PMID: 40534620; PMCID: PMC12173622.
Hanif A, Okafor DK, Katyal G, Kaur G, Ashraf H, Bodapati A, Nath TS. Shifting Rhythms: A Systematic Review Exploring the Multifaceted Effects of Shift Work and Circadian Disruption on Employee Cardiovascular Health. Cureus. 2024 Oct 7;16(10):e71003. doi: 10.7759/cureus.71003. eCollection 2024 Oct. PMID: 39507145; PMCID: PMC11539914.
Fishbein AB, Knutson KL, Zee PC. Circadian disruption and human health. J Clin Invest. 2021 Oct 1;131(19):e148286. doi: 10.1172/JCI148286. PMID: 34596053; PMCID: PMC8483747.
Lal Hind, Verma SK, Wang Y, Xie M, Young ME. Circadian Rhythms in Cardiovascular Metabolism. Circ Res. 2024 Mar 15;134(6):635-658. doi: 10.1161/CIRCRESAHA.123.323520. Epub 2024 Mar 14. PMID: 38484029; PMCID: PMC10947116.
Touitou Y, Reinberg A, Touitou D. Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption. Life Sci. 2017 Mar 15:173:94-106. doi: 10.1016/j.lfs.2017.02.008. Epub 2017 Feb 16. PMID: 28214594.
Zhao Y, Lu X, Wan F, Gao L, Lin N, He J, Wei L, Dong J, Qin Z, Zhong F, Qiao Z, Wang W, Ge H, Ding S, Yang Y, Xiu J, Shan P, Yan F, Zhao S, Ji Y, Pu J. Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction. J Am Coll Cardiol. 2022 May 31;79(21):2097-2115. doi: 10.1016/j.jacc.2022.03.370. PMID: 35618347; PMCID: PMC8972444.
Wang D, Ruan W, Chen Z, Peng Y, Li W. Shift work and risk of cardiovascular disease morbidity and mortality: A dose-response meta-analysis of cohort studies. Eur J Prev Cardiol. 2018 Aug;25(12):1293-1302. doi: 10.1177/2047487318783892. Epub 2018 Jun 22. PMID: 29929393.
Bøggild H, Knutsson A. Shift work, risk factors and cardiovascular disease. Scand J Work Environ Health. 1999 Apr;25(2):85-99. doi: 10.5271/sjweh.410. PMID: 10360463.
Seron-Ferre M, Valenzuela GJ, Torres-Farfan C. Circadian clocks during embryonic and fetal development. Birth Defects Res C Embryo Today. 2007 Sep;81(3):204-14. doi: 10.1002/bdrc.20101. PMID: 17963275.
Britz SM, Nelson S, Earhart KM, Pru JK, Schmitt EE. Circadian Disruption Impacts Fetal Development in Mice Using High-Frequency Ultrasound. J Circadian Rhythms. 2024 Dec 20:22:4. doi: 10.5334/jcr.249. eCollection 2024. PMID: 39712938; PMCID: PMC11661015.
Arrieta A, Chapski DJ, Reese A, Kimball TH, Song K, Rosa-Garrido M, Vondriska TM. Circadian control of histone turnover during cardiac development and growth. J Biol Chem. 2024 Jul;300(7):107434. doi: 10.1016/j.jbc.2024.107434. Epub 2024 Jun 1. PMID: 38830405; PMCID: PMC11261805.
Stanton DL, Zhu L, Hansen PJ. The ontogeny of circadian clock gene expression during mouse fetal development. Biochem Biophys Rep. 2025 Aug 27:44:102216. doi: 10.1016/j.bbrep.2025.102216. eCollection 2025 Dec. PMID: 40917721; PMCID: PMC12409321.
Serón-Ferré M, Natalia M, Abarzua-Catalan L, Vilches N, Valenzuela FJ, Reynolds HE, Llanos AJ, Rojas A, Valenzuela GJ, Torres-Farfan C. Circadian rhythms in the fetus. Mol Cell Endocrinol. 2012 Feb 5;349(1):68-75. doi: 10.1016/j.mce.2011.07.039. Epub 2011 Aug 5. PMID: 21840372.
Varcoe TJ, Gatford KL, Kennaway DJ. Maternal circadian rhythms and the programming of adult health and disease. Am J Physiol Regul Integr Comp Physiol. 2018 Feb 1;314(2):R231-R241. doi: 10.1152/ajpregu.00248.2017. Epub 2017 Dec 4. PMID: 29141950.
Serón-Ferré M, Torres C, Parraguez VH, Vergara M, Valladares L, Forcelledo ML, Constandil L, Valenzuela GJ. Perinatal neuroendocrine regulation. Development of the circadian time-keeping system. Mol Cell Endocrinol. 2002 Jan 25;186(2):169-73. doi: 10.1016/s0303-7207(01)00682-7. PMID: 11900892.
Oelkrug R, Harder L, Pedaran M, Hoffmann A, Beke K, Inderhees J, Gachkar S, Resch J, Johann K, Jöhren O, Krause K, Mittag J. Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring. Nat Commun. 2023 Oct 24;14(1):6742. doi: 10.1038/s41467-023-42425-w. PMID: 37875497; PMCID: PMC10597992.
Howell KR, Powell TL. Effects of maternal obesity on placental function and fetal development. Reproduction. 2017 Mar;153(3):R97-R108. doi: 10.1530/REP-16-0495. Epub 2016 Nov 18. PMID: 27864335; PMCID: PMC5432127.
Mendez N, Abarzua-Catalan L, Vilches N, Galdames HA, Spichiger C, Richter HG, Valenzuela GJ, Seron-Ferre M, Torres-Farfan C. Timed maternal melatonin treatment reverses circadian disruption of the fetal adrenal clock imposed by exposure to constant light. PLoS One. 2012;7(8):e42713. doi: 10.1371/journal.pone.0042713. Epub 2012 Aug 13. PMID: 22912724; PMCID: PMC3418288.
Yu Y, Liu JY, Yang HJ, Luo XQ, Gao XP, Huang XX, Tang AX, Cheng HYM, Liu WC, Zhang P. Circadian disruption during fetal development promotes pathological cardiac remodeling in male mice. iScience. 2024 Jan 26;27(2):109008. doi: 10.1016/j.isci.2024.109008. eCollection 2024 Feb 16. PMID: 38352228; PMCID: PMC10863319.
Zhang P, Li G, Li H, Tan X, Cheng HYM. Environmental perturbation of the circadian clock during pregnancy leads to transgenerational mood disorder-like behaviors in mice. Sci Rep. 2017 Oct 3;7(1):12641. doi: 10.1038/s41598-017-13067-y. PMID: 28974783; PMCID: PMC5626699.
Chen YL, Lin PT, Yang MY, Chuang JH. Impact of light-dark cycle on the expression of circadian clock genes, electrocardiography, and myocardial function in mice. Int J Cardiol. 2025 Sep 15:435:133418. doi: 10.1016/j.ijcard.2025.133418. Epub 2025 May 25. PMID: 40425076.
Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 2018 Jul;15(7):387-407. doi: 10.1038/s41569-018-0007-y. PMID: 29674714.
Chen F, Yang H, Fu X, Liu Z, Chen Y, Xu T, Chen Z, Luo X, Wang C, Guo Y. Research Progress of BMAL1 in Heart Failure. J Am Heart Assoc. 2025 Oct 21;14(20):e043244. doi: 10.1161/JAHA.125.043244. Epub 2025 Oct 21. PMID: 41120819.
Sayers JR, Martinez-Navarro H, Sun X, Villiers C, Sigal S, Weinberger M, Rodriguez CC, Riebel LL, Berg LA, Camps J, Herring N, Rodriguez B, Sauka-Spengler T, Riley PR. Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction. Nat Cardiovasc Res. 2025 Feb;4(2):163-179. doi: 10.1038/s44161-024-00586-x. Epub 2025 Jan 3. PMID: 39753976; PMCID: PMC11825367.
Gorabi AM, Hajighasemi S, Kiaie N, Rosano GMC, Sathyapalan T, Al-Rasadi K, Sahebkar A. Anti-fibrotic effects of curcumin and some of its analogues in the heart. Heart Fail Rev. 2020 Sep;25(5):731-743. doi: 10.1007/s10741-019-09854-6. PMID: 31512150.
Chen C, Chen P, Yu W, Zhao L, Yang Y, Qu H, Fu C, Shi D, Guo M. TGF-β-Driven Atrial Fibrosis in Atrial Fibrillation: From Mechanistic Insights to Targeted Therapies. Aging Dis. 2025 Jul 31. doi: 10.14336/AD.2025.0564. Online ahead of print. PMID: 40768638.
AlSiraj Y, Chen X, Thatcher SE, Temel RE, Cai L, Blalock E, Katz W, Ali HM, Petriello M, Deng P, Morris AJ, Wang X, Lusis AJ, Arnold AP, Reue K, Thompson K, Tso P, Cassis LA. XX sex chromosome complement promotes atherosclerosis in mice. Nat Commun. 2019 Jun 14;10(1):2631. doi: 10.1038/s41467-019-10462-z. PMID: 31201301; PMCID: PMC6643208.
Sakamuri A, Visniauskas B, Kilanowski-Doroh I, McNally AB, Imulinde A, Kamau A, Sengottaian D, McLachlan J, Anguera M, Mauvais-Jarvis F, Lindsey SH, Ogola BO. Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement. Biol Sex Differ. 2024 Jun 6;15(1):46. doi: 10.1186/s13293-024-00624-0. PMID: 38845040; PMCID: PMC11155160.
Iorga A, Cunningham CM, Moazeni S, Ruffenach G, Umar S, Eghbali M. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ. 2017 Oct 24;8(1):33. doi: 10.1186/s13293-017-0152-8. PMID: 29065927; PMCID: PMC5655818.
Zhao Z, Chang T, Liu X, Bai H, Li Z, Zhang Y, Chen H, Zhang T, Zhang Y, Lu M. Associations between the life's essential 8, genetic risk and breast cancer incidence in premenopausal and postmenopausal women: a prospective study in UK Biobank. Med Oncol. 2024 Nov 26;42(1):16. doi: 10.1007/s12032-024-02570-8. PMID: 39592495.
Stevenson JC. Mechanisms whereby oestrogens influence arterial health. Eur J Obstet Gynecol Reprod Biol. 1996 Mar;65(1):39-42. doi: 10.1016/0028-2243(95)02301-8. PMID: 8706955.
Jia H, Cui H, Zhao Z, Mo H, Zhang N, Zhang Y, Huang S, Zhang Y, Xu M, Han L, Chen Y, Chang Y, Hua X, Shentu Z, Xia T, Chen X, Song J. Abnormal circadian rhythms exacerbate dilated cardiomyopathy by reducing the ventricular mechanical strength. Cardiovasc Res. 2024 Dec 31;120(17):2261-2277. doi: 10.1093/cvr/cvae212. PMID: 39270732.
Zhou M, Zhang J, Zhao J, Liao M, Wang S, Xu D, Zhao B, Yang C, Hou G, Tan J, Liu J, Zhang W, Yin L. Sex difference in cardiac performance in individuals with irregular shift work. Int J Cardiol Cardiovasc Risk Prev. 2023 Oct 7:19:200219. doi: 10.1016/j.ijcrp.2023.200219. PMID: 37841448; PMCID: PMC10569979.
Tan JTM, Cheney CV, Bamhare NES, Hossin T, Bilu C, Sandeman L, Nankivell VA, Solly EL, Kronfeld-Schor N, Bursill CA. Female Psammomys obesus Are Protected from Circadian Disruption-Induced Glucose Intolerance, Cardiac Fibrosis and Adipocyte Dysfunction. Int J Mol Sci. 2024 Jul 1;25(13):7265. doi: 10.3390/ijms25137265. PMID: 39000372; PMCID: PMC11242371.
Jeon S, Conley S, Hollenbeak C, O'Connell M, Wang Z, Tocchi C, Redeker NS. Rest-activity rhythms predict time to hospitalizations and emergency department visits among participants in a randomized control of adults with heart failure and insomnia. Sleep Med. 2023 Aug:108:1-7. doi: 10.1016/j.sleep.2023.05.019. PMID: 37301192; PMCID: PMC10336725.
Reu K, Wiese CB. Illuminating the Mechanisms Underlying Sex Differences in Cardiovascular Disease. Circ Res. 2022 Jun 10;130(12):1747-1762. doi: 10.1161/CIRCRESAHA.122.320259. PMID: 35679362; PMCID: PMC9202078.
Hulsegge G, Gupta N, Proper KI, Lobenstein N, IJzelenberg W, Hallman DM, Holtermann A, Beek AJ. Shift work is associated with reduced heart rate variability among men but not women. Int J Cardiol. 2018 May 1:258:109-114. doi: 10.1016/j.ijcard.2018.01.089. PMID: 29433969.
Kuljis DA, Loh DH, Truong D, Vosko AM, Ong ML, McClusky R, Arnold AP, Colwell CS. Gonadal- and sex-chromosome-dependent sex differences in the circadian system. Endocrinology. 2013 Apr;154(4):1501-12. doi: 10.1210/en.2012-1921. PMID: 23439698; PMCID: PMC3602630.
Ahmed SA, Zhang B, Abdel-Rahman AA. Estrogen-mediated mitigation of cardiac oxidative stress in ovariectomized rats is associated with upregulated cardiac circadian clock Per2 and heart-specific miRNAs. Life Sci. 2023 Oct 15:331:122038. doi: 10.1016/j.lfs.2023.122038. PMID: 37619835; PMCID: PMC10528738.
Anderson ST, Meng H, Brooks TG, Tang SY, Lordan R, Sengupta A, Nayak S, Mřela A, Sarantopoulou D, Lahens NF, Weljie A, Grant GR, Bushman FD, FitzGerald GA. Sexual dimorphism in the response to chronic circadian misalignment on a high-fat diet. Sci Transl Med. 2023 May 17;15(696):eabo2022. Epub 2023 May 17. doi: 10.1126/scitranslmed.abo2022. PMID: 37196066.
Liu WX, Xie XX, Yan HC, Klinger FG, Dri M, Felici MD, Shen W, Wang BB, Cheng SF. Ablation of the circadian rhythm protein CACNA2D3 impairs primordial follicle assembly in the mouse ovary. Clin Transl Med. 2023 Nov;13(11):e1467. doi: 10.1002/ctm2.1467. PMID: 37929646; PMCID: PMC10626498.
Schroder EA, Lefta M, Zhang X, Bartos DC, Feng HZ, Zhao Y, Patwardhan A, Jin JP, Esser KA, Delisle BP. The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility. Am J Physiol Cell Physiol. 2013 May 15;304(10):C954-65. doi: 10.1152/ajpcell.00383.2012. PMID: 23364267; PMCID: PMC3651636.
Zhu C, Li S, Zhang H. Heart Failure and Arrhythmias: Circadian and Epigenetic Interplay in Myocardial Electrophysiology. Int J Mol Sci. 2025 Mar 18;26(6):2728. doi: 10.3390/ijms26062728. PMID: 40141370; PMCID: PMC11943068.
Brivio E, Kos A, Ulivi AF, Karamihalev S, Ressle A, Stoffel R, Hirsch D, Stelzer G, Schmidt MV, Lopez JP, Chen A. Sex shapes cell-type-specific transcriptional signatures of stress exposure in the mouse hypothalamus. Cell Rep. 2023 Aug 29;42(8):112874. doi: 10.1016/j.celrep.2023.112874. Epub 2023 Jul 29. PMID: 37516966.
Xu S, Huang L, Liu X, Zhang L, Wang J, Hu Y, Yang Y, Shi X, Liu C, Wang R, Miao Z, Yu Y. The transcription factor Bcl11a is essential for B-1a cell maintenance during aging. Proc Natl Acad Sci U S A. 2025 Jul 8;122(27):e2501974122. doi: 10.1073/pnas.2501974122. Epub 2025 Jul 3. PMID: 40608674; PMCID: PMC12260582.
Wren G, Davies W. Sex-linked genetic mechanisms and atrial fibrillation risk. Eur J Med Genet. 2022 Apr;65(4):104459. doi: 10.1016/j.ejmg.2022.104459. Epub 2022 Feb 19. PMID: 35189376.
Arévalo L, Gardner S, Campbell P. Haldane's rule in the placenta: Sex-biased misregulation of the Kcnq1 imprinting cluster in hybrid mice. Evolution. 2021 Jan;75(1):86-100. doi: 10.1111/evo.14132. Epub 2020 Dec 1. PMID: 33215684.
Lin S, Tzeng BH, Lee KR, Smith RJH, Campbell KP, Chen CC. Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage. Proc Natl Acad Sci U S A. 2014 May 13;111(19):E1990-8. doi: 10.1073/pnas.1323112111. Epub 2014 Apr 28. PMID: 24778262; PMCID: PMC4024911.
Veen D, Schram-Serban C, Schie M, Schaagen F, Knops P, Kavousi M, Taverne Y, Groot NMS. How sex affects the sinus rhythm heartbeat. Int J Cardiol Heart Vasc. 2023 Nov 27:49:101314. doi: 10.1016/j.ijcha.2023.101314. PMID: 38076345; PMCID: PMC10698247.
Antoun I, Layton GR, Abdelrazik A, Eldesouky M, Davies H, Barakat O, Mahfoud A, Koya A, Lau EYM, Zakkar M, Ng GA, Somani R. Unravelling Sex Disparities in the Pathophysiology of Atrial Fibrillation: Review of the Current Evidence. J Cardiovasc Electrophysiol. 2025 Oct;36(10):2608-2619. doi: 10.1111/jce.70063. PMID: 40820671; PMCID: PMC12530681.
Ghnenis A, Padmanabhan V, Vyas A. Sexual dimorphism in testosterone programming of cardiomyocyte development in sheep. Am J Physiol Heart Circ Physiol. 2022 Apr 1;322(4):H607-H621. doi: 10.1152/ajpheart.00691.2021. PMID: 35119334; PMCID: PMC8957338.
Curtis AB, Narasimha D. Arrhythmias in women. Clin Cardiol. 2012 Mar;35(3):166-71. doi: 10.1002/clc.21975. PMID: 2238912;1 PMCID: PMC6652373.
Manolio TA, Furberg CD, Rautaharju PM, Siscovick D, Newman AB, Borhani NO, Gardin JM, Tabatznik B. Cardiac arrhythmias on 24-h ambulatory electrocardiography in older women and men: the Cardiovascular Health Study. J Am Coll Cardiol. 1994 Mar 15;23(4):916-25. doi: 10.1016/0735-1097(94)90638-6. PMID: 8106697.
Giammarino L, Matas L, Alerni N, Horváth A, Vashanthakumar V, Nimani S, Barbieri M, Bains S, Lopez R, Louradour J, Ördög B, Hof T, Maguy A, Conte G, Auricchio A, Schotten U, Odening KE. Sex and sex hormonal regulation of the atrial inward rectifier potassium current (IK1): insights into potential pro-arrhythmic mechanisms. Cardiovasc Res. 2025 Jul 31;121(8):1215-1227. doi: 10.1093/cvr/cvaf074. PMID: 40272446; PMCID: PMC12310280.
Gebeily GE, Khoury NE, Mathieu S, Brouillette J, Fiset C. Estrogen regulation of the transient outward K(+) current involves estrogen receptor α in mouse heart. J Mol Cell Cardiol. 2015 Sep:86:85-94. doi: 10.1016/j.yjmcc.2015.07.013. PMID: 26205295.
Ayaz Omar, Howlett SE. Testosterone modulates cardiac contraction and calcium homeostasis: cellular and molecular mechanisms. Biol Sex Differ. 2015 Apr 29:6:9. doi: 10.1186/s13293-015-0027-9. PMID: 25922656; PMCID: PMC4411792.
Zha K, Mi B, Xiong Y, Wu S, Lu L, Zhang S, Lu X, Mak HC, Huang J, Panayi AC, Knoedler S, Chen L, Liu G, Lin S. Circadian Rhythm: Biological Functions, Diseases, and Therapeutic Targets. MedComm (2020). 2025 Oct 22;6(11):e70435. doi: 10.1002/mco2.70435. eCollection 2025 Nov. PMID: 41143275; PMCID: PMC12547082.
Ruan W, Li T, Bang IH, Lee J, Deng W, Ma X, Luo C, Du F, Yoo SH, Kim B, Li J, Yuan X, Figarella K, An YA, Wang YY, Liang Y, DeBerge M, Zhang D, Zhou Z, Wang Y, Gorham JM, Seidman JG, Seidman CE, Aranki SF, Nair R, Li L, Narula J, Zhao Z, Gorfe AA, Muehlschlegel JD, Tsai KL, Eltzschig HK. BMAL1-HIF2A heterodimer modulates circadian variations of myocardial injury. Nature. 2025 May;641(8064):1017-1028. doi: 10.1038/s41586-025-08898-z. Epub 2025 Apr 23. PMID: 40269168; PMCID: PMC12095075.
Song S, Tien CL, Cui H, Basil P, Zhu N, Gong Y, Li W, Li H, Fan Q, Choi JM, Luo W, Xue Y, Cao R, Zhou W, Ortiz AR, Stork B, Mundra V, Putluri N, York B, Chu M, Chang J, Jung SY, Xie L, Song J, Zhang L, Sun Z. Myocardial Rev-erb-Mediated Diurnal Metabolic Rhythm and Obesity Paradox. Circulation. 2022 Feb 8;145(6):448-464. doi: 10.1161/CIRCULATIONAHA.121.056076. Epub 2022 Jan 17. PMID: 35034472; PMCID: PMC8812427.
Cu Z, Xu H, Wu F, Chen J, Zhu L, Shen Z, Yi X, Yang J, Jia C, Zhang L, Zhou P, Li MJ, Zhu L, Duan S, Yao Z, Yu Y, Liu Q, Zhou J. Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells. Nat Metab. 2024 May;6(5):899-913. doi: 10.1038/s42255-024-01021-y. Epub 2024 Apr 1. PMID: 38561509.
Dong Y, Lam SM, Li Y, Li MD, Shui G. The circadian clock at the intersection of metabolism and aging - emerging roles of metabolites. J Genet Genomics. 2025 Apr 29:S1673-8527(25)00123-7. doi: 10.1016/j.jgg.2025.04.014. PMID: 40306487.
Yao N, Kinouchi K, Katoh M, Ashtiani KC, Abdelkarim S, Morimoto H, Torimitsu T, Kozuma T, Iwahara A, Kosugi S, Komuro J, Kato K, Tonomura S, Nakamura T, Itoh A, Yamaguchi S, Yoshino J, Irie J, Hashimoto H, Yuasa S, Satoh A, Mikami Y, Uchida S, Ueki T, Nomura S, Baldi P, Hayashi K, Itoh H. Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring. Cell Metab. 2025 Feb 4;37(2):395-412.e6. doi: 10.1016/j.cmet.2024.12.002. Epub 2025 Jan 14. PMID: 39814018; PMCID: PMC11872692.
Broeckaert F, Bernard A. Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. Clin Exp Allergy. 2000 Apr;30(4):469-75. doi: 10.1046/j.1365-2222.2000.00760.x. PMID: 10718843.
McAuley DF, Matthay MA. Clara cell protein CC16. A new lung epithelial biomarker for acute lung injury. Chest. 2009 Jun;135(6):1408-1410. doi: 10.1378/chest.09-0304. PMID: 19497890.
Helleday R, Segerstedt B, Forsberg B, Mudway I, Nordberg G, Bernard A, Blomberg A. Exploring the time dependence of serum clara cell protein as a biomarker of pulmonary injury in humans. Chest. 2006 Sep;130(3):672-5. doi: 10.1378/chest.130.3.672. PMID: 16963661.
Rohmann N, Stürmer P, Geisler C, Schlicht K, Knappe C, Hartmann K, Türk K, Hollstein T, Beckmann A, Seoudy AK, Becker U, Wietzke-Braun P, Settgast U, Tran F, Rosenstiel P, Beckmann JH, Schönfels W, Seifert S, Heyckendorf J, Franke A, Schreiber S, Schulte DM, Laudes M. Effects of lifestyle and associated diseases on serum CC16 suggest complex interactions among metabolism, heart and lungs. J Adv Res. 2024 May:59:161-171. doi: 10.1016/j.jare.2023.06.005. Epub 2023 Jun 16. PMID: 37330047; PMCID: PMC11081936.
Jorens PG, Sibille Y, Goulding NJ, Overveld FJ, Herman AG, Bossaert L, Backer WAD, Lauwerys R, Flower RJ, Bernard A. Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury. Eur Respir J. 1995 Oct;8(10):1647-53. doi: 10.1183/09031936.95.08101647. PMID: 8586116.
Zhou R, Yang X, Li X, Qu Y, Huang Q, Sun X, Mu D. Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis. J Neuroinflammation. 2019 Nov 27;16(1):239. doi: 10.1186/s12974-019-1651-9. PMID: 31775794; PMCID: PMC6882041.
Tian B, Yang J, Zhao Y, Ivanciuc T, Sun H, Wakamiya M, Garofalo RP, Brasier AR. Central Role of the NF-κB Pathway in the Scgb1a1-Expressing Epithelium in Mediating Respiratory Syncytial Virus-Induced Airway Inflammation. J Virol. 2018 May 14;92(11):e00441-18. doi: 10.1128/JVI.00441-18. PMID: 29593031; PMCID: PMC5952137.
Morley-Fletcher S, Mairesse J, Camp GV, Reynaert ML, Gatta E, Marrocco J, Bouwalerh H, Nicoletti F, Maccari S. Perinatal Stress Programs Sex Differences in the Behavioral and Molecular Chronobiological Profile of Rats Maintained Under a 12-h Light-Dark Cycle. Front Mol Neurosci. 2019 May 1:12:89. doi: 10.3389/fnmol.2019.00089. eCollection 2019. PMID: 31118884; PMCID: PMC6504690.
Yang D, Thiele K, Yin T, Diao L. Macrophage clock of pregnancy: circadian and metabolic control of decidual macrophage. Semin Immunopathol. 2025 Jul 18;47(1):30. doi: 10.1007/s00281-025-01057-6. PMID: 40679680.
Zhang X, Procopio SB, Ding H, Semel MG, Schroder EA, Seward TS, Du P, Wu K, Johnson SR, Prabhat Abhilash, Schneider DJ, Stumpf IG, Rozmus ER, Huo Z, Delisle BP, Esser KA. New role for cardiomyocyte Bmal1 in the regulation of sex-specific heart transcriptomes. bioRxiv [Preprint]. 2024 Apr 21:2024.04.18.590181. doi: 10.1101/2024.04.18.590181. PMID: 38659967; PMCID: PMC11042278.
Kuljis DA, Gad Laura, Loh DH, Kaswan ZMD, Hitchcock ON, Ghiani CA, Colwell CS. Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease. PLoS One. 2016 Feb 12;11(2):e0147583. doi: 10.1371/journal.pone.0147583. eCollection 2016. PMID: 26871695; PMCID: PMC4752447.
Harris EP, Abel JM, Tejada LD, Rissman EF. Calbindin Knockout Alters Sex-Specific Regulation of Behavior and Gene Expression in Amygdala and Prefrontal Cortex. Endocrinology. 2016 May;157(5):1967-79. doi: 10.1210/en.2016-1055. Epub 2016 Mar 24. PMID: 27010449; PMCID: PMC4870870.
Wu Z, Martinez ME, Hernandez A. Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues. BMC Mol Cell Biol. 2024 Mar 29;25(1):11. doi: 10.1186/s12860-024-00508-6. PMID: 38553695; PMCID: PMC10979634.
Tang J, Dong Q, Chen X. Identification of potential circadian rhythm-related hub genes and immune infiltration in preeclampsia through bioinformatics analysis. Hypertens Pregnancy. 2025 Dec 31;44(1):2559734. doi: 10.1080/10641955.2025.2559734. Epub 2025 Sep 19. PMID: 40970657.
Bhorat I. Pre-eclampsia and the foetus: a cardiovascular perspective. Cardiovasc J Afr. 2018 Nov/Dec;29(6):387-393. doi: 10.5830/CVJA-2017-039. PMID: 31199427; PMCID: PMC9048241.
Camm EJ, Botting KJ, Sferruzzi-Perri AN. Near to One's Heart: The Intimate Relationship Between the Placenta and Fetal Heart. Front Physiol. 2018 Jun 26:9:629. doi: 10.3389/fphys.2018.00629. eCollection 2018. PMID: 29997513; PMCID: PMC6029139.
Chevalley T, Dübi M, Fumeaux L, Merli MS, Sarre A, Schaer N, Simeoni U, Yzydorczyk C. Sexual Dimorphism in Cardiometabolic Diseases: From Development to Senescence and Therapeutic Approaches. Cells. 2025 Mar 20;14(6):467. doi: 10.3390/cells14060467. PMID: 40136716; PMCID: PMC11941476.
Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y, Fujii S. Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab. 2005 Jun;1(6):371-8. doi: 10.1016/j.cmet.2005.05.005. PMID: 16054086.
Flores RC, Yaffe R, Nhunzwi MM, Nguyen H, Rabinovich-Nikitin I. Maternal shift work during pregnancy and cardiovascular health impacts on mother and offspring. J Mol Cell Cardiol. 2025 Feb:199:126-132. doi: 10.1016/j.yjmcc.2024.12.008. Epub 2025 Jan 2. PMID: 39753391.
Clarkson-Townsend DA, Everson TM, Deyssenroth MA, Burt AA, Hermetz KE, Hao K, Chen J, Marsit CJ. Maternal circadian disruption is associated with variation in placental DNA methylation. PLoS One. 2019 Apr 26;14(4):e0215745. doi: 10.1371/journal.pone.0215745. eCollection 2019. PMID: 31026301; PMCID: PMC6485638.
Berg CB, Chaves I, Herzog EM, Willemsen SP, Horst GTJ, Steegers-Theunissen RPM. Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues. Chronobiol Int. 2017;34(7):921-932. doi: 10.1080/07420528.2017.1326125. Epub 2017 Jun 14. PMID: 28613964.
Suter MA, Takahashi D, Grove KL, Aagaard KM. Postweaning exposure to a high-fat diet is associated with alterations to the hepatic histone code in Japanese macaques. Pediatr Res. 2013 Sep;74(3):252-8. doi: 10.1038/pr.2013.106. Epub 2013 Jun 20. PMID: 23788059; PMCID: PMC3766448.
Galdames HA, Torres-Farfan C, Spichiger C, Mendez N, Abarzua-Catalan L, Alonso-Vazquez P, Richter HG. Impact of gestational chronodisruption on fetal cardiac genomics. J Mol Cell Cardiol. 2014 Jan:66:1-11. doi: 10.1016/j.yjmcc.2013.10.020. Epub 2013 Nov 4. PMID: 24200829.
Zavalia N, Ferraro S, Amir S. Sexually dimorphic role of circadian clock genes in alcohol drinking behavior. Psychopharmacology (Berl). 2023 Mar;240(3):431-440. doi: 10.1007/s00213-022-06247-w. Epub 2022 Oct 3. PMID: 36184679.
Shepherd R, Cheung AS, Pang K, Saffery R, Novakovic B. Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics. Front Immunol. 2021 Jan 21:11:604000. doi: 10.3389/fimmu.2020.604000. eCollection 2020. PMID: 33584674; PMCID: PMC7873844.
Tu C, Caudal A, Liu Y, Gorgodze N, Zhang H, Lam CK, Dai Y, Zhang A, Wnorowski A, Wu MA, Yang H, Abilez JO, Lyu X, Narayan SM, Mestroni L, Taylor MRG, Recchia FA, Wu JoC. Tachycardia-induced metabolic rewiring as a driver of contractile dysfunction. Nat Biomed Eng. 2024 Apr;8(4):479-494. doi: 10.1038/s41551-023-01134-x. doi: 10.1038/s41551-023-01134-x. PMID: 38012305; PMCID: PMC11088531.
Eriksson JG, Sandboge S, Salonen M, Kajantie E, Osmond C. Maternal weight in pregnancy and offspring body composition in late adulthood: findings from the Helsinki Birth Cohort Study (HBCS). Ann Med. 2015 Mar;47(2):94-9. doi: 10.3109/07853890.2015.1004360. Epub 2015 Mar 23. PMID: 25797690.