Parental Folate Deficiency Inhibits Proliferation and Increases Apoptosis of Neural Stem Cells in Rat Offspring: Aggravating Telomere Attrition as a Potential Mechanism

Abstract

The effect of maternal folate status on the fetal central nervous system (CNS) is well recognized, while evidence is emerging that such an association also exists between fathers and offspring. The biological functions of telomeres and telomerase are also related to neural cell proliferation and apoptosis. The study aimed to investigate the effect of parental folate deficiency on the proliferation and apoptosis of neural stem cells (NSCs) in neonatal offspring and the role of telomeres in this effect. In this study, rats were divided into four groups: maternal folate-deficient and paternal folate-deficient diet (D-D) group; maternal folate-deficient and paternal folate-normal diet (D-N) group; maternal folate-normal and paternal folate-deficient diet (N-D) group; and the maternal folate-normal and paternal folate-normal diet (N-N) group. The offspring were sacrificed at postnatal day 0 (PND0), and NSCs were cultured from the hippocampus and striatum tissues of offspring for future assay. The results revealed that parental folate deficiency decreased folate levels, increased homocysteine (Hcy) levels of the offspring’s brain tissue, inhibited proliferation, increased apoptosis, shortened telomere length, and aggravated telomere attrition of offspring NSCs in vivo and in vitro. In vitro experiments further showed that offspring NSCs telomerase activity was inhibited due to parental folate deficiency. In conclusion, parental folate deficiency inhibited the proliferation and increased apoptosis of offspring NSCs, maternal folate deficiency had more adverse effects than paternal, and the mechanisms may involve the telomere attrition of NSCs.

SAM/SAH Mediates Parental Folate Deficiency-Induced Neural Cell Apoptosis in Neonatal Rat Offspring: The Expression of Bcl-2, Bax, and Caspase-3

“…Our previous study demonstrated reduced folate levels in the neonatal rat offspring's brain tissue, while parental folate deficiency increased Hcy concentrations. Furthermore, the N-N group demonstrated higher folate levels and lower Hcy concentrations in offspring brain tissue than the D-N group [24]. To determine whether parental folate deficiency led to changes in neuronal apoptosis in the fetal brain through intrinsic pathways, we examined the expression of Bcl-2 family proteins (Bcl-2, Bax) via immunofluorescence.…”

“…Research we have previously conducted in rats demonstrated that parental folate deficiency decreased folate levels and increased the Hcy levels of the offspring's brain tissue [24]. Increased Hcy in fetal rat brain tissue may lead to decreased recirculation of Hcy to SAM and increased SAH levels, resulting in a decreased methylation capacity, potentially altering the biological function of the central nervous system [37].…”

“…An immunofluorescence assay was conducted as described previously [24]. The offspring brain tissue was immediately immersed in 4% PFA for 48 h, then dehydrated and embedded in paraffin.…”

Impact of varying maternal dietary folate intake on cerebellar cortex histomorphology and cell density in offspring rats

“…The changes observed indicate that folate deprivation may harm cerebellar granule cell formation and maintenance. Folate deficiency diets have been linked to cellular deterioration and apoptosis in the cerebrum (Craciunescu et al, 2004; Ren et al, 2023; Zhang et al, 2009). Similar degenerative alterations in the IGC layer were seen in a prior study that investigated the effects of maternal risperidone usage on the histology of the offspring's cerebellar cortex in a rat model (Hanafy, 2019).…”

Functional Role of Taurine in Aging and Cardiovascular Health: An Updated Overview

“…Telomere attrition limits cell ability to proliferate endlessly [190][191][192]. The enzyme telomerase reverse transcriptase (TERT) prevents critical shortening of telomere length [174].…”