Randy Given's Home Page

Randall L. Given, Ph.D

One of the critical events in early embryonic development is the establishment of a secure attachment to the uterine tissue. Without a secure attachment the embryo cannot remain in the uterus and exploit the vasculature for nutrients necessary for its further growth. Current research in our laboratory at The University of Texas Medical Branch examines the penetration of the uterine epithelium and extracellular matrix (ECM) by trophoblast during implantation in the mouse. Our current studies are investigating the effect of nicotine on the early development and invasion of the embryo.

Credentials

Research Program

The aim of these studies is to describe this invasion process, including changes in the extracellular matrix components associated with uterine epithelium and decidua. Basic developmental questions are being asked concerning the mechanisms of control of implantation and the nature of the limitations on trophoblast invasiveness imposed by the endometrium.

Mouse embryo penetrating through the uterine epithelium (between arrowheads). The embryo consists of epiblast (E), visceral (V), and Parietal (P) endoderm.

The uterine epithelium is an initial barrier to trophoblast penetration while the underlying basement membrane and decidual tissue constitute a secondary barrier to development. Although it is obvious that the basement membrane and underlying decidual layer are eventually penetrated by the trophoblast, the process of breakdown of the basement membrane and decidual ECM has not been fully characterized. In implantation sites, lysosomal activity has been localized in the degenerating epithelia and decidual tissue and type IV collagenase has been found in trophoblast. However, the actual mechanism for dissolution of the basal lamina and ECM during implantation has not been established.

Our studies involve an ultrastructural analysis of the basal lamina in specifically timed implantation sites using electron microscopy and cytochemical techniques which enhance basal lamina components. Parallel projects utilize immunolabelling techniques to localize the specific ECM components laminin, fibronectin, type IV collagen, and heparan sulfate proteoglycan and assess their distribution on the trophoblast surface, in the basal lamina, and surrounding the decidual tissue. We have established that the decidual tissue plays an important the embryo.

Other studies are investigating the effect of nicotine on the early development and invasion of the embryo. Nicotine has been implicated in changes in the ECM and has also been shown to be detrimental to early embryonic development and it may well act through alteration in ECM degradation to alter embryonic growth.

Recent Publications

Given, R.L. and Enders, A.C. The endometrium of delayed and early implantation. In: BIOLOGY OF THE UTERUS, R.M. Wynn and W.P. Jollie (eds). Plenum Publishing Corp., New York, pp. 175-231, 1989.

Blankenship, T.N.*, Given, R.L., and Parkening, T.A. Blastocyst implantation in the Chinese hamster (Cricetulus griseus). Am. J. Anat. 187:137-157, 1990.

Blankenship, T.N.* and Given, R.L. Penetration of the uterine epithelial basement membrane during blastocyst implantation in the mouse. Anat. Rec. 233:196-204, 1992.

Blankenship, T.N.* and Given, R.L. Loss of laminin and type IV collagen in the uterine epithelial basement membranes during blastocyst implantation in the mouse. Anat. Rec. In Press, 1995.

*Former Graduate Student

and Internet guidelines.

Last updated: 05/20/03