Bequer L, Fuentes E, Freyre C, Molina JL, Álvarez A, Gómez T

Language: Spanish
References: 29
Page: 21-31
PDF size: 244.30 Kb.

ABSTRACT

Objectives: Diabetes mellitus is one of the most frequent disorders of pregnancy with adverse consequences for the mother and a high risk of diabetic embryopathy in the offspring. The objective of the research was to determine the effect of pregestational diabetes with moderate hyperglycemia on maternal reproductive performance, growth, development and embryonic morphology in Wistar rats.
Materials and Methods: Longitudinal, prospective and experimental study carried out at the Biomedical Research Unit of the University of Medical Sciences of Villa Clara, Cuba. A model of neonatally induced moderate diabetes was used in female Wistar rat pups two days old, by subcutaneous administration of 100 mg/kg of body weight of streptozotocin in a single dose. At 120 days after birth, rats from both experimental groups (diabetic and control) were mated with healthy males. Weight and glycemia were determined during pregnancy and at 11,5 days the cesarean section was performed. The variables of maternal reproductive performance and of growth, development and external morphology in the embryos were analyzed. According to the results, non-parametric tests were used for the analysis of the quantitative variables and the Chi-square test for the qualitative variables.
Results: Moderate pregestational diabetes caused changes in maternal weight gain, number of resorptions, implantation sites, preimplantation loss, and implantation efficiency, as well as in morphology, size, and number of somites in embryos.
Conclusions: Moderate pregestational diabetes altered maternal reproductive performance and intrauterine growth and development of embryonic offspring. Diabetic embryopathy was also manifested by malformations of the central nervous system.

REFERENCES

1. Federación Internacional de Diabetes. Atlas de la Diabetesde la FID. 9na ed. Bruselas: Federación Internacional deDiabetes, 2019; 144.

2. Anuario Estadístico de Salud 2020. La Habana: Ministeriode salud Pública. Dirección de Registros Médicos y Estadísticasde Salud, 2021; 193.

3. Armengaud J, Simeoni U. Offspring of mothers with hyperglycemiain pregnancy: Short-term consequences fornewborns and infants. En: Lapolla A, Metzger B, editores.Gestational diabetes a decade after the HAPO Study. NewYork: Basel, Karger, 2020; 194-200.

4. Bhandari J, Thada P, Khattar D. Diabetic Embryopathy.En: StatPearls. Treasure Island: StatPearls Publishing;2021; 1-15.

5. Wentzel P, Eriksson U. Embryopathy and diabetes. En:A. Lapolla, Metzger B, editores. Gestational diabetes Adecade after the HAPO study. New York: Basel, Karger,2020; 132-44.

6. Kelstrup L, Bytoft B, Hjort L, Houshmand-Oeregaard A,Mathiesen E, Damm P, et al. Diabetes in pregnancy: Longtermcomplications of offsprings. En: Lapolla A, MetzgerB, editores. Gestational diabetes A decade after the HAPOstudy. New York: Basel, Karger, 2020; 201-22.

7. Piazza F, Segabinazi E, Ferreira A, Mega F, Dezoti C, AugustinO, et al. Severe uncontrolled maternal hyperglycemia inducesmicrosomia and neurodevelopment delay accompaniedby apoptosis, cellular survival, and neuroinflmmatoryderegulation in rat offpring hippocampus. Cell Mol Neurobiol2019; 39 (3): 401-14. doi:10.1007/s10571-019-00658-8

8. Maqbool M, Dar M, Gani I, Mir S. Animal models in diabetesmellitus: An overview. J Drug Deliv Ther 2019; 9 (1-s):472-75. doi:10.22270/jddt.v9i1-s.2351

9. Bueno A, Sinzato Y, Volpato G, Gallego F, Perecin F, RodriguesT, et al. Severity of prepregnancy diabetes on the fetalmalformations and viability associated with early embryosin rats. Biol Reprod 2020; 103 (5): 938-50. doi:10.1093/biolre/ioaa151

10. Bequer L, Gómez T, Molina J, Álvarez A, Chaviano C, ClapésS. Experimental diabetes impairs maternal reproductiveperformance in pregnant Wistar rats and their offspring.Syst Biol Reprod Med 2018; 64 (1): 60-70. doi:10.1080/19396368.2017.1395928

11. Gómez T, García M, Bequer L, Freire C, Vila M, Clapés S. Malformacionesesqueléticas y alteraciones del crecimientoen fetos de ratas con diabetes moderada. 107705/biomedica5736.2021; 41 (3): 1-7. doi:10.7705/biomedica.5736

12. Castellón D, Garcia M, Bequer L, Freire C, Molina J, BermudezA, et al. Efecto sobre el peso fetal de la suplementacióncon zinc a ratas diabeticas gestadas. Medicentro Elecrónica2021; 26 (3). Epub 01-Sep-2022. http://orcid.org/0000-0002-2761-1122

13. Aguilera B, Lecaros J, Valdés E. Ética animal: fundamentosempíricos, teóricos y dimensión práctica. Madrid: UniversidadPontificia Comillas, 2019; 393.

14. Decreto-Ley No. 31 de Bienestar Animal. Publicado enla Gaceta Oficial de la República de Cuba. (10 de abril de2021), 37.

15. York R, Parker R, Haber L. Test methods for assessing femalereproductive and developmental toxicology. 6 ed. En: HayesW, Kruger CL, editores. Hayes' Principles and methods oftoxicology. Boca Raton: Taylor & Francis; 2014; 1637-722.

16. Soulimane-Moktari N, Guermouche B, Yessoufou A, SakerM, Moutairou K, Hichami A, et al. Modulation of lipid metabolismby n−3 polyunsaturated fatty acids in gestationaldiabetic rats and their macrosomic offspring. Clin Sci 2005;109 (3): 287-95. doi:10.1042/CS20050028

17. Bueno A, Sinzato Y, Sudano M, da-Cruz F, de-Mattos I,Vieira M, et al. Short and long-term repercussions of theexperimental diabetes in embryofetal development. DiabetesMetab Res Rev 2014; 30 (7): 575-81. doi:10.1002/dmrr.2521

18. Soares T, Moraes-Souza R, Carneiro T, Araujo-Silva V,Schavinski A, Gratao T, et al. Maternal-fetal outcomesof exercise applied in rats with mild hyperglycemia afterembryonic implantation. Birth Defects Res 2020; 113 (3):287-98. doi:10.1002/bdr2.1818

19. Zabihi S, Loeken M. Understanding diabetic teratogenesis:Where are we now and where are we going? BirthDefects Res Part A-Clin Mol Teratol 2010; 88 (10): 779-90.doi:10.1002/bdra.20704

20. Coustan D. Maternal metabolic adaptation to pregnancy.En: Lapolla A, Metzger B, editores. Gestational DiabetesA Decade after the HAPO Study. New York: Basel, Karger;2020; 11-20.

21. Omolaoye T, Skosana B, du-Plessis S. Diabetes mellitusinduction:Effect of different streptozotocin doses on malereproductive parameters. Acta Histochem 2018; 120 (2):103-9. doi:10.1016/j.acthis.2017.12.005

22. Ochoa-Bernal M, Fazleabas A. Physiologic events of embryoimplantation and decidualization in human and non-humanprimates. Int J Mol Sci 2020; 21(6):1-21. doi:10.3390/ijms21061973

23. Loeken M. Mechanisms of congenital malformations inpregnancies with pre-existing diabetes. Curr Diab Rep.2020; 20(10):1-12. doi:10.1007/s11892-020-01338-4

24. Eriksson U, Wentzel P. The status of diabetic embryopathy.Ups J Med Sci 2016; 121 (2):96-112. doi:10.3109/03009734.2016.1165317

25. Fernández T, Clapés S, Suárez G, Perera A, Rodríguez V,Purón C, et al. Embriopatía diabética en ratas y efecto de unsuplemento nutricional de vitamina E durante la gestación.Rev Haban Ienc Méd 2012; 12 (2): 176-86.

26. Ornoy A, Reece A, Pavlinkova G, Kappen C, Kermit R. Effectof maternal diabetes on the embryo, fetus, and children:Congenital anomalies, genetic and epigenetic changes anddevelopmental outcomes. Birth Defects Res 2015; 105 (1):53-72. doi:10.1002/bdrc.21090

27. Carlson BM. Embriología humana y biología del desarrollo.6a ed. Barcelona: Elsevier Castellano, 2019; 496.

28. García-Sanz P, Mirasierra M, Moratalla R, Vallejo M. Embryonicdefence mechanisms against glucose-dependentoxidative stress require enhanced expression ofAlx3 toprevent malformations during diabetic pregnancy. SciRep 2017; 7 (1): 1-15. doi:10.1038/s41598-017-00334-1

29. Clapes S, Fernandez T, Prado K. El desafío para el desarrollo delsistema nervioso central en la reproducción humana asociadacon la diabetes. Rev Cubana Endocrinol 2022; 33 (1): e310.