Tai-Ho Hung1, Shih-Yin Huang2, Szu-Fu Chen3, Chung-Pu Wu4, T'sang-T'ang Hsieh5. 1. Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: thh20@cgmh.org.tw. 2. Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. 3. Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan. 4. Graduate Institute of Biomedical Sciences, Department of Physiology and Pharmacology and Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 5. Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei, Taiwan.
Abstract
INTRODUCTION: Dysregulation of placental apoptosis and autophagy are observed in pregnancy complications including preeclampsia and fetal growth restriction. However, studies of their changes in the placentas of women with gestational diabetes mellitus (GDM) show inconsistent results. We aimed to compare the changes in apoptosis, autophagy, and Bcl-2 family proteins in the placentas from women with normal pregnancies and those with GDM, with or without large-for-gestational age (LGA) infants and to investigate the effect of hyperglycemia on the changes in apoptosis, autophagy, and Bcl-2 family proteins in primary cytotrophoblastic cells. METHODS: Villous tissues were obtained from normal pregnant women and those with GDM, with or without LGA infants. Primary cytotrophoblast cells were isolated from normal term placentas and cultured under standard, hyperglycemic, or hyperosmotic conditions. RESULTS: Compared to placentas from normal pregnant women, those from GDM women with LGA infants were heavier, had lower beclin-1 and DRAM levels, less M30 and cleaved PARP immunoreactivity, and increased Ki-67 immunoreactivity. These changes were associated with increased Bcl-xL and decreased Bak levels. Increased glucose concentration led to lower ATG5, beclin-1, LC3B-II, p62, and DRAM levels, lower annexin V and M30-positive cell percentages, and less cleaved PARP changes compared with standard culture conditions. Hyperglycemia caused higher Bcl-xL levels and lower Bak and Bad levels than did standard culture conditions. DISCUSSION: There were differential changes in apoptosis and autophagy between placentas from normal pregnant women and those from GDM women with LGA infants. Bcl-2 family proteins are likely involved in the regulation of these changes.
INTRODUCTION: Dysregulation of placental apoptosis and autophagy are observed in pregnancy complications including preeclampsia and fetal growth restriction. However, studies of their changes in the placentas of women with gestational diabetes mellitus (GDM) show inconsistent results. We aimed to compare the changes in apoptosis, autophagy, and Bcl-2 family proteins in the placentas from women with normal pregnancies and those with GDM, with or without large-for-gestational age (LGA) infants and to investigate the effect of hyperglycemia on the changes in apoptosis, autophagy, and Bcl-2 family proteins in primary cytotrophoblastic cells. METHODS: Villous tissues were obtained from normal pregnant women and those with GDM, with or without LGA infants. Primary cytotrophoblast cells were isolated from normal term placentas and cultured under standard, hyperglycemic, or hyperosmotic conditions. RESULTS: Compared to placentas from normal pregnant women, those from GDMwomen with LGA infants were heavier, had lower beclin-1 and DRAM levels, less M30 and cleaved PARP immunoreactivity, and increased Ki-67 immunoreactivity. These changes were associated with increased Bcl-xL and decreased Bak levels. Increased glucose concentration led to lower ATG5, beclin-1, LC3B-II, p62, and DRAM levels, lower annexin V and M30-positive cell percentages, and less cleaved PARP changes compared with standard culture conditions. Hyperglycemia caused higher Bcl-xL levels and lower Bak and Bad levels than did standard culture conditions. DISCUSSION: There were differential changes in apoptosis and autophagy between placentas from normal pregnant women and those from GDMwomen with LGA infants. Bcl-2 family proteins are likely involved in the regulation of these changes.