Department of Obstetrics and Gynecology, E-Da Hospital, 6 Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, #100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
Reprod Sci. 2021 Mar;28(3):877-887. doi: 10.1007/s43032-020-00308-1. Epub 2020 Sep 9.
The objective of this research is to study the effects of TGF-β1 inhibition on endometrial receptivity and pregnancy outcomes in mice with adenomyosis. Experiments were done using a mouse model of adenomyosis which took place in a hospital-affiliated laboratory. The mouse model used for this research is ICR mouse. Adenomyosis was induced by oral gavage of tamoxifen (TAM) from postnatal days (PNDs) 1 to 4 in ICR mice. Bilateral intrauterine injection of anti-TGF-β1-neutralizing antibody or isotype IgG or PBS was performed at PND42. The mice were then either sacrificed or mated at PND64 followed by sacrificing at gestational day (GD) 4 or proceeding to delivery. Implantation numbers, rate of dams with live birth, live birth numbers, survival at 1 week old, and pup mortality rate after weaning were recorded. Collagen was demonstrated by Masson's trichrome and Van Gieson's stains. Uterine expression of a receptivity marker, leukemia inhibitory factor (LIF), was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry (IHC). Anti-TGF-β1 treatment increased the mean implantation numbers, fecundity rate, the rate of dams with live birth, pup survival rate at 1 week old, and pup mortality rate after weaning. Collagen expression in uteri with adenomyosis was attenuated by anti-TGF-β1 treatment. Increased LIF expression by anti-TGF-β1 treatment was detected by qRT-PCR, Western blot, and IHC. The results suggest that inhibition of TGF-β1 improves pregnancy outcomes by restoring endometrial receptivity in mice with adenomyosis.
本研究旨在探讨 TGF-β1 抑制对子宫腺肌病小鼠子宫内膜容受性和妊娠结局的影响。实验在医院附属实验室使用子宫腺肌病小鼠模型进行。该研究使用的小鼠模型为 ICR 小鼠。通过在 ICR 小鼠产后第 1 至 4 天经口灌胃他莫昔芬（TAM）诱导子宫腺肌病模型。在 PND42 时对小鼠进行双侧子宫内注射抗 TGF-β1 中和抗体或同种型 IgG 或 PBS。然后在 PND64 处死或交配，随后在妊娠第 4 天处死或继续分娩。记录着床数、活产母鼠比例、活产数、1 周龄存活率和断奶后幼仔死亡率。通过 Masson 三色和 Van Gieson 染色显示胶原蛋白。通过定量逆转录聚合酶链反应（qRT-PCR）、Western blot 和免疫组织化学（IHC）检测接受性标志物白血病抑制因子（LIF）在子宫中的表达。抗 TGF-β1 治疗增加了平均着床数、生育力、活产母鼠比例、1 周龄幼仔存活率和断奶后幼仔死亡率。抗 TGF-β1 治疗减弱了子宫腺肌病小鼠子宫内的胶原蛋白表达。通过 qRT-PCR、Western blot 和 IHC 检测到抗 TGF-β1 治疗增加了 LIF 的表达。这些结果表明，抑制 TGF-β1 通过恢复子宫内膜容受性来改善子宫腺肌病小鼠的妊娠结局。
