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Steroids Modulate the Expression of ₄ Integrin in Mouse Blastocysts and Uterus During Implantation¹

^a Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India

Blastocyst implantation and successful establishment of pregnancy require delicate interactions between the embryo and the maternal uterine milieu, which are controlled at the embryo-maternal interface by the coordinated interplay of a variety of growth factors, cytokines, hormones, and cell adhesion molecules expressed by both the decidualized endometrium and the trophoblast cells. Proper implantation of the embryo is solely dependent on the initial endometrial receptivity and the preparation of the blastocyst to glue itself to the uterine wall. Both these events are considered to be mediated by cell adhesion molecules and integrins expressed by the blastocyst as well by as the maternal endometrium. Integrin expression by the blastocyst and the uterus is a dynamic process. However, reports on the expression and the hormonal modulation of integrins and their role in blastocyst activation and uterine receptivity during implantation are meager. The present study investigates the expression and hormonal regulation of ₄ß₁ integrin by steroid hormones in the blastocyst and the receptive uterus using an in vivo, delayed-implantation mouse model system. The dormant and activated blastocysts as well as the uteri were recovered from ovariectomized mice after progesterone-alone and progesterone-plus-estrogen therapy, respectively. Immunolocalization of protein expression of ₄ and ß₁ integrin subunits indicate that steroids modulate the expression of ₄ß₁ integrin receptor in the mouse blastocyst as well as the uterus and that a differential expression is observed with exposure to progesterone and estrogen. Intrauterine blocking of ₄ integrin by specific antibody resulted in implantation failure in normal as well as in delayed-implantation mice. Based on our data, we propose here, to our knowledge for the first time, that ₄ß₁ integrin, which is responsible for binding to fibronectin and vascular cell adhesion molecule-1, is induced by estradiol and is down-regulated by progesterone in mice during implantation. Furthermore, the results also indicate the direct role of ₄ integrin in the process of implantation.

First decision: 12 June 2001.

¹ Supported by grants from the Indo-French Center for Promotion of Advanced Research, New Delhi, India. Fellowships provided by the Indian Council of Medical Research and Council of Scientific and Industrial Research to S.B. and R.D., respectively, are gratefully acknowledged.

² Correspondence. FAX: 91 11 6862663; chandana_d{at}hotmail.com

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