Ageing, a modulator of human endometrial stromal cell proliferation and decidualization: a role for implantation?

Research question: Does ageing affect endometrial stromal cell function and gene expression involved in decidualization? Design: Stromal cells were isolated and cultured (98% purity) from pipelle endometrial biopsies obtained from female donors, at the proliferative phase of the menstrual cycle. Initially, 28 samples were collected (age range 25–46 years). These samples were divided into two groups: 25–35 years and 36–46 years. Cell proliferation assays were carried out to determine changes in stromal cell proliferation, in vitro, between the two groups. In addition, mRNA and protein expression of decidualization factors, BMP2 and STAT3, were analysed for the same age groups and samples using real-time polymerase chain reaction and western blot analysis, respectively. Finally, another 12 pipelle endometrial biopsies (age range 25–46 years) were used in separate in-vitro decidualization experiments. The mRNA expression of decidualization markers, prolactin and IGFBP-1 were analysed in cultured stromal cells after adding 8-bromo-cAMP. Results: A statistically significant decrease was observed in stromal cell proliferation with increasing age (P = 0.0006). Messenger RNA expression of BMP2 and STAT3 were found to decrease (P = 0.0167; P = 0.0037, respectively) in the older age group. In addition, BMP2 and STAT3 protein expression between the samples analysed changed significantly (P = 0.0085; P = 0.0463, respectively) with increasing age. In-vitro induced decidualization experiments showed significant changes in stromal cell mRNA expression of decidualization markers (IGFBP1 and prolactin) between different age groups. Conclusion: Ageing affected endometrial cell function and gene expression. Changes in cell function and expression of associated molecules that differ in the ageing endometrium can help understand the causes of infertility.