PARENT SESSION
IMPLANTATION AND PREGNANCY - B

Tuesday, August 3, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(519) DECIDUAL PROLACTIN-RELATED PROTEIN GENE TARGETING: INSIGHTS INTO EXPRESSION AND BIOLOGICAL ACTIONS.

Konno, Toshihiro¹, Alam, S.M. Khorshed¹, Dai, Gouli¹, Lu, Lu¹, Wang, Danhua¹, Dunmore, Judy¹, Godwin, Alan¹, Soares, Michael¹, ¹ University of Kansas Medical Center, Kansas City, Kansas

ABSTRACT- In the mouse, decidual cells differentiate from the uterine stroma in response to steroid hormones and signals arising from the embryo. Decidual cells are critically involved in creating the intrauterine environment conducive to embryonic development. Among their many functions is the production of cytokines related to prolactin (PRL), including decidual PRL-related protein (dPRP). DPRP is a heparin-binding cytokine, which predominates in the decidua from day 6 to day 11 of pregnancy. In this investigation, we have isolated the mouse dPRP gene, characterized its structure, and generated mutant mice containing a knock-in of the enhanced green fluorescent protein (EGFP) gene into the dPRP gene. Exons 2-6 of the mouse dPRP gene were replaced with the EGFP gene, such that the locus encodes a dPRP-EGFP fusion protein that lacks dPRP function. Heterozygous intercross breeding of the mutant mice yielded the expected Mendelian ratio (1:2:1). Furthermore, pregnant heterozygote females express EGFP within decidual tissue in locations identical to endogenous dPRP mRNA and protein expression. Homozygous dPRP null mutant male and female mice are viable, exhibit normal postnatal growth rates, and are fertile. DPRP null mutants show some increased variability in their rates of development. This was most easily observed at day 7.5 of gestation through measurement of the amniotic cavity. Mean cross-sectional areas of amniotic cavities from dPRP null conceptuses were significantly greater than found in wild-type conceptuses (0.81±0.37 versus 0.19±0.06 mm²). DPRP deficiency also affected decidual cell gene expression. In summary our experiments have yielded new insights about the biology of dPRP: 1) the mouse dPRP gene locus can be used to direct decidual-specific gene expression; 2) the dPRP gene encodes for a cytokine that influences decidual cell gene expression and the timing of amniotic cavity formation. (T.K. and S.M.K.A. contributed equally; supported by HD39878 and the Hall Family Foundation)

KEY WORDS: prolactin, pregnancy, decidua, implantation