Progesterone depletion results in Lamin B1 loss and induction of cell death in mouse trophoblast giant cells

Abstract

Trophoblast giant cells (TGCs), a mouse trophoblast subtype, have large amounts of cytoplasm and high ploidy levels via endocycles. The diverse functions and gene expression profiles of TGCs have been studied well, but their nuclear structures remain unknown. In this study, we focus on Lamin B1, a nuclear lamina, and clarify its expression dynamics, regulation and roles in TGC functions. TGCs that differentiated from trophoblast stem cells were used. From days 0 to 9 after differentiation, the number of TGCs gradually increased, but the amount of LMNB1 peaked at day 3 and then slightly decreased. An immunostaining experiment showed that LMNB1-depleted TGCs increased after day 6 of differentiation. These LMNB1-depleted TGCs diffused peripheral localization of the heterochromatin marker H3K9me2 in the nuclei. However, LMINB1-knock down was not affected TGCs specific gene expression. We found that the death of TGCs also increased after day 6 of differentiation. Moreover, Lamin B1 loss and the cell death in TGCs were protected by 10−6 M progesterone. Our results conclude that progesterone protects against Lamin B1 loss and prolongs the life and function of TGCs.