Abstract
The endometrium in early pregnancy undergoes decidualization and functional changes induced by local trophoblast, which are not fully understood. We hypothesized that endometrium from tubal ectopic pregnancy (EP) could be interrogated to identify novel genes and pathways involved in these processes. Gestation-matched endometrium was collected from women with EP (n = 11) and intrauterine pregnancies (IUP) (n = 13). RNA was extracted from the tissue. In addition, tissues were prepared for histological analysis for degree of decidualization. We compared a) the samples from EP that were decidualized (n = 6) with non-decidualized samples (n = 5), and b) the decidualized EP (n = 6) with decidualization-matched IUP (n = 6) samples using an Affymetrix gene array platform, with Ingenuity Pathway Analysis, combined with quantitative RT-PCR. Expression of PRL and IGFBP1 was used to confirm the degree of decidualization in each group. There were no differences in PRL or IGFBP1 expression in the decidualization-matched samples but a marked reduction (P<0.001) in the non-decidualized samples. Decidualization was associated with increased expression of 428 genes including SCARA5 (181-fold), DKK1 (71-fold) and PROK1 (32-fold), and decreased expression of 230 genes including MMP-7 (35-fold) and SFRP4 (21-fold). The top canonical pathways associated with these differentially expressed genes were Natural Killer Cell and Wnt/b-Catenin signaling. Local trophoblast was associated with much less alteration of endometrial gene expression with an increase in 56 genes, including CSH1 (8-fold), and a reduction in 29 genes including CRISP3 (8-fold). The top associated canonical pathway was Antigen Presentation. The study of endometrium from tubal EP may promote novel insights into genes involved in decidualization and those influenced by factors from neighboring trophoblast. This has afforded unique information not highlighted by previous studies and adds to our understanding of the endometrium in early pregnancy.
Highlights
Transformation of the endometrial lining of the uterus into decidua is an essential requirement for blastocyst implantation in women [1]
It was clear that one cluster represented the highly decidualized samples and these were all from intrauterine pregnancies
It is not known if trophoblast locally affects or regulates the process of decidualization in early pregnancy or what paracrine effects the trophoblast may have on the endometrium
Summary
Transformation of the endometrial lining of the uterus into decidua is an essential requirement for blastocyst implantation in women [1]. Normal placentation will fail in the absence of endometrial decidualization [2]. Unlike other mammalian species, the decidual transformation of the endometrium does not require blastocyst attachment and invasion. It commences in the secretory phase of the menstrual cycle under the influence of progesterone and continues if pregnancy occurs [3]. It is still not clear what role local trophoblast factors may have in this process
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