Female Reproductive Tract

Embryo-Uterine Interactions via the Neuregulin Family of Growth Factors During Implantation in the Mouse

Abstract
Neuregulins (NRGs) are cell-signaling molecules with recognized roles in cancer and development, but little is known about their role in embryo implantation. Among representative NRG-1 isoforms, neu differentiation factor (NDF/type I) is expressed in the female reproductive tract and is localized to the implantation site. Here, we show that sensory and motor neuron-derived factor (SMDF/type III) is expressed in the uterine subepithelial stroma around the blastocyst and is only upregulated at the time of implantation. The cellular distribution of SMDF is similar to NDF and requires the presence of an implantation-competent blastocyst. The glial growth factor (GGF/type II) isoform of NRG-1 and the NRG-2 and NRG-3 genes were not found to be expressed in the periimplantation uterus by RT-PCR or in situ hybridization. In contrast to the cellular expression pattern of NDF and SMDF, NRG-4 was present in the luminal and glandular epithelium throughout the uterus during the pre-implantation period. NRG-4 expression declined in the uterine luminal epithelium during implantation but persisted in the glandular epithelium through day 8 of pregnancy. Studies in ovariectomized mice showed that NRG-4 is a progesterone-regulated gene, with partial augmentation by estrogen. We also observed upregulation of the erbB2 and erbB3 receptors at the blastocyst stage of embryo development. Together, these findings suggest that a distinct subset of NRGs participate in the signaling network that directs embryo implantation. Upregulation of embryonic erbB2/erbB3 in the blastocyst trophectoderm and the induction of certain NRG-1 isoforms with blastocyst activation help define additional aspects of the embryo-uterine crosstalk that underlie the implantation process.

Key words: Growth factors • Implantation • Uterus

This article has been cited by other articles:

				I. Koscinski, S. Viville, N. Porchet, A. Bernigaud, F. Escande, A. Defossez, and M.-P. Buisine MUC4 gene polymorphism and expression in women with implantation failure Hum. Reprod., September 1, 2006; 21(9): 2238 - 2245. [Abstract] [Full Text] [PDF]