Regulation of gap junction connexins in the endometrium during early pregnancy

Abstract

In mammalian species embryo implantation into uterine tissue is restricted to a limited time period, the receptive phase. For successful implantation appropriate differentiation of the receptive endometrium is under the control of ovarian steroid hormones. In addition, locally acting embryonic signals are needed to modulate the maternal environment before invasion of the trophoblast is permitted. The expression pattern of gap junction channel proteins, connexins (cx), is directly related to this process. In rodents as well as in rabbit and humans the receptive endometrium is characterized by a lack of such cell-to-cell communication channels. In the rat endometrium cx26 is suppressed in the epithelium and cx43 in the stromal compartment by maternal progesterone, a phenomenon that can be observed similarly in human endometrium. Experimental approaches revealed that both connexin genes react very sensitively to progesterone and estrogen treatment. In rat and rabbit connexin expression is induced locally in the endometrium in response to the implanting blastocyst. In both species this induction of connexins can be mimicked by a traumatic stimulus. In conclusion, suppression of connexin expression in the endometrium is a characteristic cell biological indication for receptivity in different species. The limited induction of direct cell-to-cell communication properties, probably due to locally acting blastocyst signals, seems to be a precondition for embryo implantation.