Jin Min, Lv Ping-Ping, Yu Tian-Tian, Shen Jin-Ming, Feng Chun, Huang He-Feng
The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
Biol Reprod. 2016 Nov;95(5):96. doi: 10.1095/biolreprod.116.141242. Epub 2016 Sep 14.
Our previous study indicated that maternal high-estrogen environment in the first trimester is correlated with increased risks of low birth weight (LBW) and adult diseases. The present study aimed to establish an animal model to confirm such an effect in mice, and to further explore the mechanism involved. A mouse model with high estradiol (E) exposure during early pregnancy was established, and the birth weight, growth after birth, and expression levels of insulin-like growth factor-binding protein 1 (IGFBP1) of pups were examined. Meanwhile, IGFBP1 expression after treatment of E was examined in a HepG2 hepatoma cell line. We found that after exposure to a high-E environment the weight of the pups decreased significantly, not only before but also after birth. Meanwhile, both mRNA and protein expressions of IGFBP1 were elevated in placenta and liver tissues. Furthermore, the level of IGFBP1 in the HepG2 cell line was elevated by the treatment of E, whereas this effect was blocked by estrogen receptor antagonist ICI 182780. In summary, maternal high estrogen up-regulates expression of IGFBP1 in placenta and fetal livers, which contributes to LBW and decreases body weight in offspring.
我们之前的研究表明，孕早期母体的高雌激素环境与低出生体重（LBW）及成人疾病风险增加相关。本研究旨在建立一个动物模型以在小鼠中证实这种效应，并进一步探究其中涉及的机制。建立了孕早期暴露于高雌二醇（E）的小鼠模型，并检测了幼崽的出生体重、出生后的生长情况以及胰岛素样生长因子结合蛋白1（IGFBP1）的表达水平。同时，在HepG2肝癌细胞系中检测了E处理后IGFBP1的表达。我们发现，暴露于高E环境后，幼崽的体重显著下降，不仅在出生前，出生后也是如此。同时，胎盘和肝脏组织中IGFBP1的mRNA和蛋白表达均升高。此外，E处理可使HepG2细胞系中IGFBP1的水平升高，而雌激素受体拮抗剂ICI 182780可阻断这种效应。总之，母体高雌激素上调胎盘和胎儿肝脏中IGFBP1的表达，这导致低出生体重并降低后代体重。
