Progesterone-regulated B4galnt2 expression is a requirement for embryo implantation in mice

Objective

To investigate B4galnt2 gene regulation in the female mouse reproductive system (B4galnt2 encodes an enzyme, β1,4-N-acetylgalactosylaminyltransferase II, that catalyzes the addition of GalNAc to glycoproteins via a β1,4 linkage).

Design

Experimental prospective study.

Setting

Research institute and university.

Animal(s)

Outbred Institute for Cancer Research (ICR) mice.

Intervention(s)

Subcutaneous injection of P/E₂; uterine tissues were collected after a 3-day injection period and were collected at different times during pregnancy.

Main Outcome Measure(s)

Gene expression was measured by quantitative real-time polymerase chain reaction after hormonal treatment of ovariectomized mice or pregnant mice. Primary endometrial cell cultivation and a gene promoter assay were used for P regulation analysis. The small interfering RNA (siRNA) technique was used to assess the gene function in embryo implantation in vivo.

Result(s)

Animal experiments, a primary endometrial cell cultivation assay, and a gene promoter assay indicated that B4galnt2 is regulated positively by P and negatively by estrogen. B4galnt2 was expressed in uterine tissue at peri-implantation (embryonic day 3.5) along with a sharp increase in placental P production at embryonic day 10.5, and declined as estrogen increased during pregnancy. Using the siRNA in vivo implantation assay, we have proved that B4galnt2 participated in embryonic implantation during pregnancy in mice.

Conclusion(s)

This study shows for the first time the expression of B4galnt2 in pregnant mice and its regulation by P. We conclude that the naturally occurring up-regulation of B4galnt2 during pregnancy contributes to normal embryo implantation but not to embryo development.