Molecules in blastocyst implantation: Uterine and embryonic perspectives

Lim, Hyunjung Jade; Song, Haengseok; Paria, Bibhash C.; Reese, Jeff; Das, Sanjoy K.; Dey, S. K.

doi:10.1016/s0083-6729(02)64002-6

Cited by 93 publications

(65 citation statements)

References 127 publications

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“…It is well documented that the effects of P 4 and E 2 are either synergistic or antagonistic with respect to various uterine functions and gene expression (5,24). Therefore, it was obligatory to determine whether increasing the P 4 doses would counteract the Fig.…”

Section: Discussionmentioning

confidence: 99%

Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation

Song²,

Das³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Many underlying causes of human infertility have been overcome by using in vitro fertilization (IVF) and embryo transfer (ET) techniques. Nevertheless, implantation rates in IVF programs remain low despite the transfer of apparently healthy embryos. This suggests that there are problems with the differentiation of the uterus to the receptive state in response to the ovarian hormones estrogen and progesterone. The molecular basis of this receptive state when the uterine environment is conducive to blastocyst acceptance and implantation remains poorly understood. Normally, the ''window'' of uterine receptivity lasts for a limited time. Using ETs and the progesterone-treated delayed-implantation model in mice, we demonstrate here that levels of estrogen within a very narrow range determine the duration of the window of uterine receptivity. Although estrogen at different physiological concentrations can initiate implantation, we find that the window of uterine receptivity remains open for an extended period at lower estrogen levels but rapidly closes at higher levels. The uterine refractoriness that follows the receptive state at high estrogen levels is accompanied by aberrant uterine expression of implantation-related genes. These results suggest that careful regulation of estrogen levels is one of the important factors for improvement of female fertility in IVF͞ET programs.

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Section: Discussionmentioning

confidence: 99%

Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation

Song²,

Das³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

460

334

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“…Immediate anchoring to endometrial epithelial cells after hatching may be disadvantageous for embryos to maintain an adequate period of cross-talk, regulating their attachment at an appropriate site and orientation (Simón et al, 2001;Lim et al, 2002). However, the mechanisms by which embryos are prevented from premature anchoring have remained largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Even after opening the window, before attachment to the endometrial luminal epithelial cells, it has been widely accepted that there is crosstalk between the embryo and maternal tissues in order for implantation to occur at an appropriate site in the uterine cavity and at an appropriate time following a process called apposition (Simón et al, 2001;Lim et al, 2002). To strictly regulate these periods, it is reasonable to assume that not only adhesive forces but also repulsive forces play a role in this event, regulating the close interface between the hatched blastocyst and maternal endometrium.…”

Section: Introductionmentioning

confidence: 99%

Eph–ephrin A system regulates murine blastocyst attachment and spreading

Fujii

Tatsumi

Kosaka

et al. 2006

Developmental Dynamics

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Although numerous adhesion molecules are expressed on mammalian endometrial epithelial cells, there have not been any studies of a mechanism to prevent premature attachment of the embryo. In this study, we examined the possible involvement of Eph-ephrin interaction, which can induce repulsive forces. In mice, Eph A1, A2, and A4 were expressed on endometrial epithelial cells and ephrin A1-4 on blastocysts. Reverse transcriptase-polymerase chain reaction showed that mRNA expression of ephrin A1-4 on embryos transiently decreased around the implantation period. Immunohistochemistry demonstrated that the expression of Eph A1 on endometrial epithelial cells and ephrin A1 and A3 expression on embryos decreased at implantation sites. Recombinant Eph A1 reacted with cell the surface of ephrin A-bearing trophectoderm cells. Attachment assays using Eph A1-coated dishes showed that blastocyst attachment was reversibly inhibited by Eph A1. These findings suggest an important role of the Eph-ephrin A system in regulating the initial embryo-maternal contact during the cross-talk period that precedes embryo implantation.

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“…As endometrium is a regenerative tissue it is subjected to proliferation, secretion and degeneration on monthly basis. Nearly all morphologic and biochemical processes that the uterus undergoes during its acquisition of receptivity are directly or indirectly regulated by ovarian steroid hormones (Lim et al, 2002). The development of human endometrium is divided into follicular and luteal phase.…”

Section: The Role Of E2 and P4 In Human Endometriummentioning

confidence: 99%

“…During the follicular phase ovarian E2 is produced with increasing quantities until ovulation, stimulating the proliferation and growth of the epithelial and stromal components of the endometrium. During the luteal phase the increasing amounts of the P4 and secondary maintaining levels of E2 are both involved in the differentiation of the endometrium but P4 reverses the proliferative effects of E2 (Lim et al, 2002). Together, coordinated action of steroid hormones produced by the follicle and corpus luteum prepare the endometrium every month for potential embryo implantation.…”

Section: The Role Of E2 and P4 In Human Endometriummentioning

confidence: 99%