TGF-β1 Neutralization Improves Pregnancy Outcomes by Restoring Endometrial Receptivity in Mice with Adenomyosis.

Abstract

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 1week 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 1week 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.