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Progesterone supplementation extends uterine receptivity for blastocyst implantation in mice

¹ Departments of Pathology and Immunology, ² Obstetrics and Gynecology, Washington University School of Medicine, 4566 Scott Avenue, St Louis, Missouri 63110, USA, ³ Laboratory of Reproductive Biology and Infertility, Sungkyunkwan University School of Medicine, Cheil General Hospital and Women’s Healthcare Center, 1-19, Mukjeong-dong, Jung-gu, Seoul 100-380, South Korea and ⁴ Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, South Korea

Correspondence should be addressed to H Lim, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, South Korea; Email: hlim{at}konkuk.ac.kr

We previously showed that blastocyst can initiate implantation beyond the normal ‘window’ of uterine receptivity on day 5 of pregnancy and pseudopregnancy (PSP) in mice. In this study, we investigated whether uterine receptivity for blastocyst implantation can be further extended on day 6 of PSP and the role of progesterone (P₄) on this event. Embryo transfers, experimentally induced decidualization, in situ hybridization and [³H]thymidine incorporation were performed. Blastocysts initiate attachment reaction within 48 h when transferred on day 5, but not on day 6 of PSP. Likewise, decidualization reaction occurred on days 4 and 5 of PSP, but completely failed on day 6. However, P₄ supplementation partially retains uterine receptivity for blastocyst implantation and decidualization on day 6 of PSP. In addition, certain indicators of uterine receptivity, such as cell proliferation profile and expression patterns of implantation-related genes were similarly observed on days 4 and 5 of PSP, but not on day 6. Consistent with embryo transfer and decidualization, exogenous administration of P₄ partially restores these indicators on day 6 of PSP. We concluded that critical physiological changes occur between days 4 and 5 of PSP, leading to uterine non-receptivity on day 6, but P₄ is able to extend the uterine receptivity through day 6.