Xia Dandan, Xu Xun, Zhang Yuhui, Zhang Chenying, Wang Huiyan
Department of Obstetrics and Gynecology, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16# DingXiang Rd, ZhongLou District, Changzhou, 213000, China.
Changzhou Key Laboratory of Maternal and Child Health Medicine, Changzhou, Jiangsu, 213000, China.
Reprod Sci. 2025 Aug 12. doi: 10.1007/s43032-025-01946-z.
Gestational diabetes mellitus (GDM) leads to macrosomia primarily due to fat accumulation caused by adipocyte differentiation. This study aims to investigate the role and underlying mechanisms of Chromatin assembly factor 1 subunit A (CHAF1A) in GDM-induced macrosomia. CHAF1A expression was compared between the GDM with macrosomia group (n = 25) and the normal glucose with normal weight group (n = 15), and the correlation between CHAF1A and neonatal body composition was examined. CHAF1A was overexpressed and knocked down in human visceral preadipocytes (HPA-v), and the effects on cell proliferation and adipogenic differentiation were measured, then the expressions of adipogenic markers were determined. Transcriptome sequencing was employed to investigate the potential mechanisms. Placental immunohistochemistry showed that the expression of CHAF1A in the GDM with macrosomia group was significantly higher than that in the control group (P < 0.05). Correlation analysis showed that CHAF1A expression was positively correlated with neonatal weight, body fat percentage, and fat mass. In functional assays, preadipocytes overexpressing CHAF1A showed enhanced proliferation and adipogenic differentiation, while knockdown of CHAF1A resulted in the opposite effect. Moreover, CHAF1A affected the expression of adipogenic markers. Transcriptome sequencing analysis showed that the differentially expressed genes after CHAF1A silencing were enriched in signaling pathways closely related to preadipocyte differentiation and hormone secretion and synthesis, such as JAK-STAT, Wnt and BMP signaling pathways. CHAF1A promotes the proliferation and differentiation of preadipocytes, which may be a direction for exploring fetal fat accumulation leading to macrosomia in GDM.
妊娠期糖尿病（GDM）主要由于脂肪细胞分化导致的脂肪堆积而引起巨大儿。本研究旨在探讨染色质组装因子1亚基A（CHAF1A）在GDM诱导的巨大儿中的作用及潜在机制。比较了巨大儿GDM组（n = 25）和正常体重正常血糖组（n = 15）中CHAF1A的表达，并检测了CHAF1A与新生儿身体组成之间的相关性。在人内脏前脂肪细胞（HPA-v）中过表达和敲低CHAF1A，检测其对细胞增殖和成脂分化的影响，然后测定成脂标志物的表达。采用转录组测序研究潜在机制。胎盘免疫组化显示，巨大儿GDM组中CHAF1A的表达明显高于对照组（P < 0.05）。相关性分析显示，CHAF1A表达与新生儿体重、体脂百分比和脂肪量呈正相关。在功能试验中，过表达CHAF1A的前脂肪细胞显示出增强的增殖和成脂分化，而敲低CHAF1A则产生相反的效果。此外，CHAF1A影响成脂标志物的表达。转录组测序分析显示，CHAF1A沉默后差异表达的基因富集于与前脂肪细胞分化以及激素分泌和合成密切相关的信号通路，如JAK-STAT、Wnt和BMP信号通路。CHAF1A促进前脂肪细胞的增殖和分化，这可能是探索GDM中导致巨大儿的胎儿脂肪堆积的一个方向。
