Neonatal Genistein Exposure Causes Implantation Failure by Disrupting Uterine Developmental Patterning and Endometrial Gland Formation. Neonatal Genistein Exposure Causes Implantation Failure by Disrupting Uterine Developmental Patterning and Endometrial Gland Formation

Female mice exposed neonatally to the phytoestrogen genistein (GEN) at doses similar to those in infants consuming soy-based infant formulas are infertile due in part to uterine implantation defects. To determine the mechanisms by which neonatal GEN exposure causes implantation defects, female mice were exposed to vehicle (corn oil) or GEN in corn oil (50 mg/kg/day) on postnatal days (PND) 1-5. Uterine tissues were collected during early gestation for microarray analysis; gestation day 1.5 (GD1.5), GD3.5, GD4.5 and GD5.5. We conclude that neonatal GEN exposure disrupts expression of genes important for uterine development, causing posteriorization and diminished gland function during pregnancy that together cause implantation failure. Overall design: CD-1 mice were exposed to corn oil as controls (CON) or genistein (GEN) at a dose of 50 mg/kg/day on postnatal days 1-5. Uteri were collected on gestation day 1.5 (GD1.5), GD3.5, GD4.5 or GD5.5

新生期暴露于植物雌激素（phytoestrogen）染料木黄酮（genistein，GEN）、暴露剂量与食用大豆基婴儿配方奶粉的婴儿摄入剂量相近的雌性小鼠，其不育表型部分源于子宫着床缺陷。为明确新生期GEN暴露引发着床缺陷的分子机制，研究人员于出生后第1至5天（postnatal days, PND）对雌性CD-1小鼠分别施以溶剂对照（玉米油）或玉米油配制的GEN溶液（50 mg/kg/天）处理。在妊娠早期收集子宫组织，用于微阵列芯片（microarray）分析，采样时间点涵盖妊娠第1.5天（gestation day 1.5, GD1.5）、GD3.5、GD4.5及GD5.5。本研究证实，新生期GEN暴露会干扰子宫发育相关基因的表达，进而引发妊娠期间子宫后极化与腺体功能减退，二者共同导致着床失败。整体实验设计：将CD-1小鼠分为两组，对照组（CON）予以玉米油处理，染毒组给予50 mg/kg/天的GEN处理，处理周期为出生后第1至5天。分别于GD1.5、GD3.5、GD4.5及GD5.5收集子宫组织。