Folate deficiency decreases apoptosis of endometrium decidual cells in pregnant mice via the mitochondrial pathway

• Published in: Nutrients Vol. 7; no. 3; pp. 1916 - 1932
• Main Authors: Liao, Xing Gui, Li, Yan Li, Gao, Ru Fei, Geng, Yan Qing, Chen, Xue Mei, Liu, Xue Qing, Ding, Yu Bin, Mu, Xin Yi, Wang, Ying Xiong, He, Jun Lin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2015; MDPI
• Subjects: Animals; Apoptosis; bcl-2-Associated X Protein - metabolism; Cell death; Cytochrome; Cytochromes c - metabolism; Decidua - physiopathology; decidual cells; Diet; Embryo Implantation - physiology; Endometrium; Female; folate deficiency; Folic Acid - blood; Folic Acid Deficiency - blood; Folic Acid Deficiency - physiopathology; Laboratory animals; Membrane Potential, Mitochondrial; Mice; Mitochondria - physiology; Pregnancy; Pregnancy Complications - blood; Pregnancy Complications - physiopathology; Pregnancy, Animal; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Stromal Cells; Uterus; Vagina; Vitamin B; Vitamin deficiency
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu7031916

It is well known that maternal folate deficiency results in adverse pregnancy outcomes. In addition to aspects in embryonic development, maternal uterine receptivity and the decidualization of stromal cells is also very important for a successful pregnancy. In this study, we focused on endometrium decidualization and investigated whether apoptosis, which is essential for decidualization, was impaired. Flow cytometry and TUNEL detection revealed that apoptosis of mouse endometrium decidual cells was suppressed in the dietary folate-deficient group on Days 7 and 8 of pregnancy (Day 1 = vaginal plug) when decidua regression is initiated. The endometrium decidual tissue of the folate deficiency group expressed less Bax compared to the normal diet group while they had nearly equal expression of Bcl2 protein. Further examination revealed that the mitochondrial transmembrane potential (ΔΨm) decreased, and the fluorescence of diffuse cytoplasmic cytochrome c protein was detected using laser confocal microscopy in normal decidual cells. However, no corresponding changes were observed in the folate-deficient group. Western blotting analyses confirmed that more cytochrome c was released from mitochondria in normal decidual cells. Taken together, these results demonstrated that folate deficiency could inhibit apoptosis of decidual cells via the mitochondrial apoptosis pathway, thereby restraining decidualization of the endometrium and further impairing pregnancy.