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Impact of Maternal Gestational Methyl Donor Deficiency on Reproductive Development and Fertility of Mice Offspring
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1786172
*Corresponding author: (email:singhd@nirrch.res.in).
► gestational methyl donor deficiency
► gonadal development
► F1 offspring
► Sub-fertility
Abstract
Background: Emergence of metabolic disorders (obesity, type 2 diabetes, etc.) may originate at early development, explained by “The Developmental Origins of Health and Disease (DOHaD)” but it does not explicit reproductive disorders origin. This study aims to disentangle offspring’s reproductive development and fertility due to gestational methyl-donor (vitamin B12, folic acid, and methionine) deficiency.
Materials and methods: Pregnant OCT4-GFP mice, fed on control chow diet (CCD) and 40% methyl-donor deficient diet (MDD) from gestation day (GD) 5 to GD20. Reproductive development was studied on gestation day GD18, post-natal day (PND) 22 and PND60. Fertility study was done by mating adult F1 male offspring with adult female mice on standard diet.
Results: Teratological defects are observed in pups of 40% MDD group with few mortalities. Testicular histology was significantly impaired in 40% MDD group at GD18, PND22, and PND60. Quantitative histomorphometry and immunofluorescence study showed the loss of spermatogonia and spermatocytes with significant increase in germ cells sloughing and seminiferous tubules atrophy. Apoptosis is also observed in seminiferous tubules by TUNEL assay. Copulation index, sperm count, and motility were significantly reduced in case of the 40% MDD group at adulthood. The F1 offspring of this group were sub-fertile with significant post-implantation loss.
Conclusion: The study suggests that gestational methyl donor deficiency has pernicious effects on gonadal development. The sexual development and maturation influenced by reduction in epididymal sperm count and sperm motility along with development of teratological defects in offspring. Fertility study evidenced sub-fertility in F1 offspring.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (email:singhd@nirrch.res.in).
Keywords
► gestational methyl donor deficiency
► gonadal development
► F1 offspring
► Sub-fertility
Abstract
Background: Emergence of metabolic disorders (obesity, type 2 diabetes, etc.) may originate at early development, explained by “The Developmental Origins of Health and Disease (DOHaD)” but it does not explicit reproductive disorders origin. This study aims to disentangle offspring’s reproductive development and fertility due to gestational methyl-donor (vitamin B12, folic acid, and methionine) deficiency.
Materials and methods: Pregnant OCT4-GFP mice, fed on control chow diet (CCD) and 40% methyl-donor deficient diet (MDD) from gestation day (GD) 5 to GD20. Reproductive development was studied on gestation day GD18, post-natal day (PND) 22 and PND60. Fertility study was done by mating adult F1 male offspring with adult female mice on standard diet.
Results: Teratological defects are observed in pups of 40% MDD group with few mortalities. Testicular histology was significantly impaired in 40% MDD group at GD18, PND22, and PND60. Quantitative histomorphometry and immunofluorescence study showed the loss of spermatogonia and spermatocytes with significant increase in germ cells sloughing and seminiferous tubules atrophy. Apoptosis is also observed in seminiferous tubules by TUNEL assay. Copulation index, sperm count, and motility were significantly reduced in case of the 40% MDD group at adulthood. The F1 offspring of this group were sub-fertile with significant post-implantation loss.
Conclusion: The study suggests that gestational methyl donor deficiency has pernicious effects on gonadal development. The sexual development and maturation influenced by reduction in epididymal sperm count and sperm motility along with development of teratological defects in offspring. Fertility study evidenced sub-fertility in F1 offspring.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India