Gestational diabetus mellitus and its complications, role of desynchronosis in pathogenesis (a review)
DOI:
https://doi.org/10.14739/2310-1237.2023.2.282626Keywords:
desynchronosis, gestational diabetes, diabetic cardiomyopathies, liverAbstract
Diabetes mellitus is the most common metabolic disorder during pregnancy. The International Diabetes Federation estimates that one in six pregnant women (16.8 %) has diabetes. The prevalence of this disease in the human population is striking and, according to various sources, accounts for 14–25 % of all pregnant women. Most cases of hyperglycemia during pregnancy (75–90 %) is due to gestational diabetes mellitus (GDM).
Risk factors, etiology and pathophysiology of GDM are being actively studied, but there are still some controversial issues. For example, the development of GDM in the aspect of circadian rhythm disorders. This problem is especially relevant in connection with pregnancy. After all, there is a two-way relationship here – circadian rhythm disorders affect the course of pregnancy, and pregnancy can be the cause of these disorders. In addition, this problem is relevant for women with a history of endocrine disorders, including diabetes mellitus, as there is a clear link between circadian rhythms and the production of hormones, including insulin.
The aim of this review was to show the relationship between the development of GDM, its complications, and circadian rhythm disorders in women.
Pregnancy complicated by GDM can have a negative effect on the myocardium and liver. Moreover, this disease has a significant impact on the myocardium of the offspring. GDM also can cause other complications for the mother’s health and fetus or newborn. Scientists have identified a fairly significant number of risk factors for GDM. However, circadian rhythm disorders accompanying pregnancy are often underestimated as a risk factor.
In general, there are many controversies regarding the relationship between long / short sleep duration and quality and the risk of developing diabetes, as well as how melatonin and its precursor serotonin affect metabolism in critical organs. Thus, the role of circadian rhythm disorders in the development of diabetes and its consequences is not yet fully understood. It is likely that solving the problem of circadian rhythm disorders will be the key to overcoming a significant proportion of cases of GDM. Therefore, there is an urgent need for further, larger-scale studies to investigate the causal links between circadian rhythm disorders, diabetes mellitus, and pregnancy.
References
- International Diabetes Federation. (2017). IDF Diabetes Atlas (8th ed.). IDF: Brussels, Belgium. https://diabetesatlas.org/atlas/eighth-edition/
- World Health Organization (2016). Global report on diabetes. WHO Library Cataloguing-in-Publication Data. https://apps.who.int/iris/bitstream/handle/10665/204871/9?sequence=1
- Schliefsteiner, C., Hirschmugl, B., Kopp, S., Curcic, S., Bernhart, E. M., Marsche, G., Lang, U., Desoye, G., & Wadsack, C. (2017). Maternal Gestational Diabetes Mellitus increases placental and foetal lipoprotein-associated Phospholipase A2 which might exert protective functions against oxidative stress. Scientific reports, 7(1), 12628. https://doi.org/10.1038/s41598-017-13051-6
- Wu, J. N., Gu, W. R., Xiao, X. R., Zhang, Y., Li, X. T., & Yin, C. M. (2019). Gestational weight gain targets during the second and third trimesters of pregnancy for women with gestational diabetes mellitus in China. European journal of clinical nutrition, 73(8), 1155-1163. https://doi.org/10.1038/s41430-018-0358-9
- Katra, P., Dereke, J., Nilsson, C., & Hillman, M. (2016). Plasma Levels of the Interleukin-1-Receptor Antagonist Are Lower in Women with Gestational Diabetes Mellitus and Are Particularly Associated with Postpartum Development of Type 2 Diabetes. PloS one, 11(5), e0155701. https://doi.org/10.1371/journal.pone.0155701
- Plows, J. F., Stanley, J. L., Baker, P. N., Reynolds, C. M., & Vickers, M. H. (2018). The Pathophysiology of Gestational Diabetes Mellitus. International journal of molecular sciences, 19(11), 3342. https://doi.org/10.3390/ijms19113342
- Gooley, J. J., Mohapatra, L., & Twan, D. C. K. (2017). The role of sleep duration and sleep disordered breathing in gestational diabetes mellitus. Neurobiology of sleep and circadian rhythms, 4, 34-43. https://doi.org/10.1016/j.nbscr.2017.11.001
- Cai, S., Tan, S., Gluckman, P. D., Godfrey, K. M., Saw, S. M., Teoh, O. H., Chong, Y. S., Meaney, M. J., Kramer, M. S., Gooley, J. J., & GUSTO study group (2017). Sleep Quality and Nocturnal Sleep Duration in Pregnancy and Risk of Gestational Diabetes Mellitus. Sleep, 40(2), 10.1093/sleep/zsw058. https://doi.org/10.1093/sleep/zsw058
- Facco, F. L., Grobman, W. A., Reid, K. J., Parker, C. B., Hunter, S. M., Silver, R. M., Basner, R. C., Saade, G. R., Pien, G. W., Manchanda, S., Louis, J. M., Nhan-Chang, C. L., Chung, J. H., Wing, D. A., Simhan, H. N., Haas, D. M., Iams, J., Parry, S., & Zee, P. C. (2017). Objectively measured short sleep duration and later sleep midpoint in pregnancy are associated with a higher risk of gestational diabetes. American journal of obstetrics and gynecology, 217(4), 447.e1-447.e13. https://doi.org/10.1016/j.ajog.2017.05.066
- Zhu, C., Yang, H., Geng, Q., Ma, Q., Long, Y., Zhou, C., & Chen, M. (2015). Association of oxidative stress biomarkers with gestational diabetes mellitus in pregnant women: a case-control study. PloS one, 10(4), e0126490. https://doi.org/10.1371/journal.pone.0126490
- Kramer, C. K., Campbell, S., & Retnakaran, R. (2019). Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis. Diabetologia, 62(6), 905-914. https://doi.org/10.1007/s00125-019-4840-2
- Buddeberg, B. S., Sharma, R., O'Driscoll, J. M., Kaelin Agten, A., Khalil, A., & Thilaganathan, B. (2020). Impact of gestational diabetes mellitus on maternal cardiac adaptation to pregnancy. Ultrasound in obstetrics & gynecology, 56(2), 240-246. https://doi.org/10.1002/uog.21941
- Oliveira, A. P., Calderon, I. M., Costa, R. A., Roscani, M. G., Magalhães, C. G., & Borges, V. T. (2015). Assessment of structural cardiac abnormalities and diastolic function in women with gestational diabetes mellitus. Diabetes & vascular disease research, 12(3), 175-180. https://doi.org/10.1177/1479164114563302
- Chung, E., & Leinwand, L. A. (2014). Pregnancy as a cardiac stress model. Cardiovascular research, 101(4), 561-570. https://doi.org/10.1093/cvr/cvu013
- Rospleszcz, S., Schafnitzel, A., Koenig, W., Lorbeer, R., Auweter, S., Huth, C., Rathmann, W., Heier, M., Linkohr, B., Meisinger, C., Hetterich, H., Bamberg, F., & Peters, A. (2018). Association of glycemic status and segmental left ventricular wall thickness in subjects without prior cardiovascular disease: a cross-sectional study. BMC cardiovascular disorders, 18(1), 162. https://doi.org/10.1186/s12872-018-0900-7
- Chung, E., Yeung, F., & Leinwand, L. A. (2013). Calcineurin activity is required for cardiac remodelling in pregnancy. Cardiovascular research, 100(3), 402-410. https://doi.org/10.1093/cvr/cvt208
- Verma, N., Srodulski, S., Velmurugan, S., Hoskins, A., Pandey, V. K., Despa, F., & Despa, S. (2021). Gestational diabetes triggers postpartum cardiac hypertrophy via activation of calcineurin/NFAT signaling. Scientific reports, 11(1), 20926. https://doi.org/10.1038/s41598-021-00422-3
- Parra, V., & Rothermel, B. A. (2017). Calcineurin signaling in the heart: The importance of time and place. Journal of molecular and cellular cardiology, 103, 121-136. https://doi.org/10.1016/j.yjmcc.2016.12.006
- Appiah, D., Schreiner, P. J., Gunderson, E. P., Konety, S. H., Jacobs, D. R., Jr, Nwabuo, C. C., Ebong, I. A., Whitham, H. K., Goff, D. C., Jr, Lima, J. A., Ku, I. A., & Gidding, S. S. (2016). Association of Gestational Diabetes Mellitus With Left Ventricular Structure and Function: The CARDIA Study. Diabetes care, 39(3), 400-407. https://doi.org/10.2337/dc15-1759
- Savitz, D. A., Danilack, V. A., Elston, B., & Lipkind, H. S. (2014). Pregnancy-induced hypertension and diabetes and the risk of cardiovascular disease, stroke, and diabetes hospitalization in the year following delivery. American journal of epidemiology, 180(1), 41-44. https://doi.org/10.1093/aje/kwu118
- Echouffo-Tcheugui, J. B., Guan, J., Retnakaran, R., & Shah, B. R. (2021). Gestational Diabetes and Incident Heart Failure: A Cohort Study. Diabetes care, 44(10), 2346-2352. Advance online publication. https://doi.org/10.2337/dc21-0552
- Triggle, C. R., Ding, H., Marei, I., Anderson, T. J., & Hollenberg, M. D. (2020). Why the endothelium? The endothelium as a target to reduce diabetes-associated vascular disease. Canadian journal of physiology and pharmacology, 98(7), 415-430. https://doi.org/10.1139/cjpp-2019-0677
- Li, X., Sun, X., & Carmeliet, P. (2019). Hallmarks of Endothelial Cell Metabolism in Health and Disease. Cell metabolism, 30(3), 414-433. https://doi.org/10.1016/j.cmet.2019.08.011
- Kluge, M. A., Fetterman, J. L., & Vita, J. A. (2013). Mitochondria and endothelial function. Circulation research, 112(8), 1171-1188. https://doi.org/10.1161/CIRCRESAHA.111.300233
- Meng, T., Qin, W., & Liu, B. (2020). SIRT1 Antagonizes Oxidative Stress in Diabetic Vascular Complication. Frontiers in endocrinology, 11, 568861. https://doi.org/10.3389/fendo.2020.568861
- McElwain, C. J., Tuboly, E., McCarthy, F. P., & McCarthy, C. M. (2020). Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?. Frontiers in endocrinology, 11, 655. https://doi.org/10.3389/fendo.2020.00655
- Huang-Doran, I., Zhang, C. Y., & Vidal-Puig, A. (2017). Extracellular Vesicles: Novel Mediators of Cell Communication In Metabolic Disease. Trends in endocrinology and metabolism: TEM, 28(1), 3-18. https://doi.org/10.1016/j.tem.2016.10.003
- Kereliuk, S. M., Xiao, F., Burger, D., & Dolinsky, V. W. (2022). Extracellular Vesicles as an Index for Endothelial Injury and Cardiac Dysfunction in a Rodent Model of GDM. International journal of molecular sciences, 23(9), 4970. https://doi.org/10.3390/ijms23094970
- Franzago, M., Lanuti, P., Fraticelli, F., Marchioni, M., Buca, D., Di Nicola, M., Liberati, M., Miscia, S., Stuppia, L., & Vitacolonna, E. (2021). Biological insight into the extracellular vesicles in women with and without gestational diabetes. Journal of Endocrinological Investigation, 44(1), 49-61. https://doi.org/10.1007/s40618-020-01262-0
- Salomon, C., Scholz-Romero, K., Sarker, S., Sweeney, E., Kobayashi, M., Correa, P., Longo, S., Duncombe, G., Mitchell, M. D., Rice, G. E., & Illanes, S. E. (2016). Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation. Diabetes, 65(3), 598-609. https://doi.org/10.2337/db15-0966
- Arias, M., Monteiro, L. J., Acuña-Gallardo, S., Varas-Godoy, M., Rice, G. E., Monckeberg, M., Díaz, P., & Illanes, S. E. (2019). Vesículas extracelulares como predictores tempranos de diabetes gestacional [Extracellular vesicle concentration in maternal plasma as an early marker of gestational diabetes]. Revista medica de Chile, 147(12), 1503-1509. https://doi.org/10.4067/S0034-98872019001201503
- Zhang, Y., Feng, J., Wang, Q., Zhao, S., Yang, S., Tian, L., Meng, P., Li, J., & Li, H. (2018). Hyperglycaemia Stress-Induced Renal Injury is Caused by Extensive Mitochondrial Fragmentation, Attenuated MKP1 Signalling, and Activated JNK-CaMKII-Fis1 Biological Axis. Cellular physiology and biochemistry, 51(4), 1778-1798. https://doi.org/10.1159/000495681
- Wang, D., Liu, C., Liu, X., Zhang, Y., & Wang, Y. (2021). Evaluation of prenatal changes in fetal cardiac morphology and function in maternal diabetes mellitus using a novel fetal speckle-tracking analysis: a prospective cohort study. Cardiovascular ultrasound, 19(1), 25. https://doi.org/10.1186/s12947-021-00256-z
- Godoy-Matos, A. F., Silva Júnior, W. S., & Valerio, C. M. (2020). NAFLD as a continuum: from obesity to metabolic syndrome and diabetes. Diabetology & metabolic syndrome, 12, 60. https://doi.org/10.1186/s13098-020-00570-y
- You, S. Y., Han, K., Lee, S. H., & Kim, M. K. (2021). Nonalcoholic fatty liver disease and the risk of insulin-requiring gestational diabetes. Diabetology & metabolic syndrome, 13(1), 90. https://doi.org/10.1186/s13098-021-00710-y
- Ye, W., Luo, C., Huang, J., Li, C., Liu, Z., & Liu, F. (2022). Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis. BMJ, 377, e067946. https://doi.org/10.1136/bmj-2021-067946
- Zhu, H., Chen, B., Cheng, Y., Zhou, Y., Yan, Y. S., Luo, Q., Jiang, Y., Sheng, J., Ding, G., & Huang, H. F. (2019). Insulin therapy for gestational diabetes mellitus does not fully protect offspring from diet-induced metabolic disorders. Diabetes, 68(4), 696-708. https://doi.org/10.2337/db18-1151
- Giannakou, K., Evangelou, E., Yiallouros, P., Christophi, C. A., Middleton, N., Papatheodorou, E., & Papatheodorou, S. I. (2019). Risk factors for gestational diabetes: An umbrella review of meta-analyses of observational studies. PloS one, 14(4), e0215372. https://doi.org/10.1371/journal.pone.0215372
- Lee, K. W., Ching, S. M., Ramachandran, V., Yee, A., Hoo, F. K., Chia, Y. C., Wan Sulaiman, W. A., Suppiah, S., Mohamed, M. H., & Veettil, S. K. (2018). Prevalence and risk factors of gestational diabetes mellitus in Asia: a systematic review and meta-analysis. BMC pregnancy and childbirth, 18(1), 494. https://doi.org/10.1186/s12884-018-2131-4
- Sciarra, F., Franceschini, E., Campolo, F., Gianfrilli, D., Pallotti, F., Paoli, D., Isidori, A. M., & Venneri, M. A. (2020). Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility. International journal of molecular sciences, 21(11), 3943. https://doi.org/10.3390/ijms21113943
- Crosby, P., & Partch, C. L. (2020). New insights into non-transcriptional regulation of mammalian core clock proteins. Journal of cell science, 133(18), jcs241174. https://doi.org/10.1242/jcs.241174
- Goldstein, C. A., & Smith, Y. R. (2016, December 1). Sleep, Circadian Rhythms, and Fertility. Current Sleep Medicine Reports, 2, 206-217. https://doi.org/10.1007/s40675-016-0057-9
- Espino, J., Macedo, M., Lozano, G., Ortiz, Á., Rodríguez, C., Rodríguez, A. B., & Bejarano, I. (2019). Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment. Antioxidants (Basel, Switzerland), 8(9), 338. https://doi.org/10.3390/antiox8090338
- Fernando, S., Biggs, S. N., Horne, R. S. C., Vollenhoven, B., Lolatgis, N., Hope, N., Wong, M., Lawrence, M., Lawrence, A., Russell, C., Leong, K., Thomas, P., Rombauts, L., & Wallace, E. M. (2018). The impact of melatonin on the sleep patterns of women undergoing IVF: a double blind RCT. Human reproduction open, 2017(4), hox027. https://doi.org/10.1093/hropen/hox027
- Sen, A., & Hoffmann, H. M. (2020). Role of core circadian clock genes in hormone release and target tissue sensitivity in the reproductive axis. Molecular and cellular endocrinology, 501, 110655. https://doi.org/10.1016/j.mce.2019.110655
- Zheng, Y., Liu, C., Li, Y., Jiang, H., Yang, P., Tang, J., Xu, Y., Wang, H., & He, Y. (2019). Loss-of-function mutations with circadian rhythm regulator Per1/Per2 lead to premature ovarian insufficiency†. Biology of reproduction, 100(4), 1066-1072. https://doi.org/10.1093/biolre/ioy245
- Lateef, O. M., & Akintubosun, M. O. (2020). Sleep and Reproductive Health. Journal of circadian rhythms, 18, 1. https://doi.org/10.5334/jcr.190
- Caetano, G., Bozinovic, I., Dupont, C., Léger, D., Lévy, R., & Sermondade, N. (2021). Impact of sleep on female and male reproductive functions: a systematic review. Fertility and sterility, 115(3), 715-731. https://doi.org/10.1016/j.fertnstert.2020.08.1429
- Rahman, S. A., Grant, L. K., Gooley, J. J., Rajaratnam, S. M. W., Czeisler, C. A., & Lockley, S. W. (2019). Endogenous Circadian Regulation of Female Reproductive Hormones. The Journal of clinical endocrinology and metabolism, 104(12), 6049-6059. https://doi.org/10.1210/jc.2019-00803
- Shao, S., Zhao, H., Lu, Z., Lei, X., & Zhang, Y. (2021). Circadian Rhythms Within the Female HPG Axis: From Physiology to Etiology. Endocrinology, 162(8), bqab117. https://doi.org/10.1210/endocr/bqab117
- Mindell, J. A., Cook, R. A., & Nikolovski, J. (2015). Sleep patterns and sleep disturbances across pregnancy. Sleep medicine, 16(4), 483-488. https://doi.org/10.1016/j.sleep.2014.12.006
- Juulia Paavonen, E., Saarenpää-Heikkilä, O., Pölkki, P., Kylliäinen, A., Porkka-Heiskanen, T., & Paunio, T. (2017). Maternal and paternal sleep during pregnancy in the Child-sleep birth cohort. Sleep medicine, 29, 47-56. https://doi.org/10.1016/j.sleep.2016.09.011
- Man, G. C. W., Zhang, T., Chen, X., Wang, J., Wu, F., Liu, Y., Wang, C. C., Cheong, Y., & Li, T. C. (2017). The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy-An immunological perspective. American journal of reproductive immunology, 78(2), 10.1111/aji.12715. https://doi.org/10.1111/aji.12715
- Ejaz, H., Figaro, J. K., Woolner, A. M. F., Thottakam, B. M. V., & Galley, H. F. (2021). Maternal Serum Melatonin Increases During Pregnancy and Falls Immediately After Delivery Implicating the Placenta as a Major Source of Melatonin. Frontiers in endocrinology, 11, 623038. https://doi.org/10.3389/fendo.2020.623038
- Firneisz, G., Rosta, K., Al-Aissa, Z., Hadarits, O., Harreiter, J., Nádasdi, Á., Bancher-Todesca, D., Németh, L., Igaz, P., Rigó, J., Jr, Sziller, I., Kautzky-Willer, A., & Somogyi, A. (2018). The MTNR1B rs10830963 Variant in Interaction with Pre-Pregnancy BMI is a Pharmacogenetic Marker for the Initiation of Antenatal Insulin Therapy in Gestational Diabetes Mellitus. International journal of molecular sciences, 19(12), 3734. https://doi.org/10.3390/ijms19123734
- Nisa, H., Qi, K. H. T., Leng, J., Zhou, T., Liu, H., Li, W., Wang, L., Li, N., Hu, G., & Qi, L. (2018). The Circadian Rhythm-Related MTNR1B Genotype, Gestational Weight Gain, and Postpartum Glycemic Changes. The Journal of clinical endocrinology and metabolism, 103(6), 2284-2290. https://doi.org/10.1210/jc.2018-00071
- Laste, G., Silva, A. A. D., Gheno, B. R., & Rychcik, P. M. (2021). Relationship between melatonin and high-risk pregnancy: A review of investigations published between the years 2010 and 2020. Chronobiology international, 38(2), 168-181. https://doi.org/10.1080/07420528.2020.1863975
- Xu, Y. H., Shi, L., Bao, Y. P., Chen, S. J., Shi, J., Zhang, R. L., & Lu, L. (2018). Association between sleep duration during pregnancy and gestational diabetes mellitus: a meta-analysis. Sleep medicine, 52, 67-74. https://doi.org/10.1016/j.sleep.2018.07.021
- Wang, H., Leng, J., Li, W., Wang, L., Zhang, C., Li, W., Liu, H., Zhang, S., Chan, J., Hu, G., Yu, Z., & Yang, X. (2017). Sleep duration and quality, and risk of gestational diabetes mellitus in pregnant Chinese women. Diabetic medicine, 34(1), 44-50. https://doi.org/10.1111/dme.13155
- Zhang, X., Zhang, R., Cheng, L., Wang, Y., Ding, X., Fu, J., Dang, J., Moore, J., & Li, R. (2020). The effect of sleep impairment on gestational diabetes mellitus: a systematic review and meta-analysis of cohort studies. Sleep medicine, 74, 267-277. https://doi.org/10.1016/j.sleep.2020.05.014
- Facco, F. L., Parker, C. B., Reddy, U. M., Silver, R. M., Koch, M. A., Louis, J. M., Basner, R. C., Chung, J. H., Nhan-Chang, C. L., Pien, G. W., Redline, S., Grobman, W. A., Wing, D. A., Simhan, H. N., Haas, D. M., Mercer, B. M., Parry, S., Mobley, D., Hunter, S., Saade, G. R., … Zee, P. C. (2017). Association Between Sleep-Disordered Breathing and Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus. Obstetrics and gynecology, 129(1), 31-41. https://doi.org/10.1097/AOG.0000000000001805
- Bourjeily, G., Danilack, V. A., Bublitz, M. H., Lipkind, H., Muri, J., Caldwell, D., Tong, I., & Rosene-Montella, K. (2017). Obstructive sleep apnea in pregnancy is associated with adverse maternal outcomes: a national cohort. Sleep medicine, 38, 50-57. https://doi.org/10.1016/j.sleep.2017.06.035
- Balserak, B. I., Zhu, B., Grandner, M. A., Jackson, N., & Pien, G. W. (2019). Obstructive sleep apnea in pregnancy: performance of a rapid screening tool. Sleep & breathing = Schlaf & Atmung, 23(2), 425-432. https://doi.org/10.1007/s11325-018-1724-5
- Newbold, R., Benedetti, A., Kimoff, R. J., Meltzer, S., Garfield, N., Dasgupta, K., Gagnon, R., Lavigne, L., Olha, A., Rey, E., & Pamidi, S. (2021). Maternal Sleep-Disordered Breathing in Pregnancy and Increased Nocturnal Glucose Levels in Women with Gestational Diabetes Mellitus. Chest, 159(1), 356-365. https://doi.org/10.1016/j.chest.2020.07.014
- Asuaje Pfeifer, M., Liebmann, M., Beuerle, T., Grupe, K., & Scherneck, S. (2022). Role of Serotonin (5-HT) in GDM Prediction Considering Islet and Liver Interplay in Prediabetic Mice during Gestation. International journal of molecular sciences, 23(12), 6434. https://doi.org/10.3390/ijms23126434
- Klishch, І. М., Bezkorovayna, H. О., & Khara, М. R. (2019). Aktyvnist perekysnoho okysnennia lipidiv ta antyoxydantnoho zakhystu miokarda tvaryn riznoi stati pry poshkodzenni adrenalinom na tli svitlovoho desynkhronozu [The activity of lipid peroxidation and antioxidant protection of the myocardium of different sex animals at adrenaline damage on the background of light desynchronosis]. Klinichna ta eksperymentalna patolohiia, 18(4), 30-35. [in Ukrainian]. https://doi.org/10.24061/1727-4338.XVIII.4.70.2019.5
- Khara, M. R., Bezkorovaina, H. O., Klishch, I. M., & Pelykh, V. Ye. (2020). Sex differences in the cardiac cholinergic response to adrenalin-induced myocardial necrosis and light desynchronosis. Pathologia, 17(2), 142-148. https://doi.org/10.14739/2310-1237.2020.2.212727
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