Citation: Erkenbrack, E. M., Maziarz, J., Griffith, O. W., Liang, C., Chavan, A. R., Nnamani, M., & Wagner, G. P. (2016). The mammalian decidual cell evolved from a cellular stress response. PLOS Biol 16(8): e2005594.
Placental invasion into the maternal endometrium of the uterus shows substantial similarities to early cancer dissemination into stroma1,2,3,4. These similarities have inspired the hypothesis of antagonistic pleiotropy5,6. According to this hypothesis, trophoblasts evolved the capacity to invade the endometrium, leading to invasive placentation. These mechanisms can become reactivated in cancer cells, leading to a predisposition to metastasis. This implies that cancer malignancy should be limited to placental mammals where invasive placentation first evolved. This prediction, however, is inconsistent with the fact that opossums, with ancestrally non-invasive placenta7,8, get invasive skin cancers9. Here, we explore an alternative scenario in which stromal cells of the uterus evolved to either resist or permit invasion, determining the outcome of placental invasiveness9.
Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional Programs
Decidual stromal cells differentiate from endometrial stromal fibroblasts (ESFs) under the influence of progesterone and cyclic adenosine monophosphate (cAMP) and are essential for implantation and the maintenance of pregnancy. They evolved in the stem lineage of placental (eutherian) mammals coincidental with the evolution of implantation. Here we use the well-established in vitro decidualization protocol to compare early (3 days) and late (8 days) gene transcription patterns in immortalized human ESF. We document extensive, dynamic changes in the early and late decidual cell transcriptomes. The data suggest the existence of an early signal transducer and activator of transcription (STAT) pathway dominated state and a later nuclear factor kB (NFKB) pathway regulated state. Transcription factor expression in both phases is characterized by putative or known progesterone receptor (PGR) target genes, suggesting that both phases are under progesterone control. Decidualization leads to proliferative quiescence, which is reversible by progesterone withdrawal after 3 days but to a lesser extent after 8 days of decidualization. In contrast, progesterone withdrawal induces cell death at comparable levels after short or long exposure to progestins and cAMP. We conclude that decidualization is characterized by a biphasic gene expression dynamic that likely corresponds to different phases in the establishment of the fetal–maternal interface.
© 2018 Eric M Erkenbrack et al. All rights reserved.