Endometrial gland secretions are essential for successful embryo implantation. Gland development occurs during the proliferative phase and lays the foundation for the later receptive phase. Despite its importance little is known regarding the impact of endometrial gland regeneration in determining female fertility or infertility. We hypothesised that gland formation during the proliferative phase is altered in infertile women. Our aim was to compare the cytokine profile and gland density during the proliferative phase of fertile and infertile women.
Area of the glandular epithelium (GE) as a percentage of total area was determined in endometrial tissue sections collected from fertile (n=19) and infertile (n=14) women. The expression of 41 cytokines in proliferative phase uterine fluid of fertile (n=15) and infertile (n=15) women was measured using Luminex immunoassay. The samples were further grouped according to age; fertile <35 years (n=5), fertile ≥35 years (n=10), infertile <35 years (n=7) and infertile ≥35 years (n=8). Cellular localisation of transforming growth factor alpha (TGFα) and interferon gamma (IFNγ) within the proliferative phase endometrium; fertile (n=15) and infertile (n=11) was examined using immunohistochemistry.
There was no significant difference in GE area of infertile women compared to fertile. Interleukin-1 alpha (IL-1α) was significantly increased (p=0.034) in infertile compared to fertile women. Significant elevation of CCL11 (p=0.048), TGFα (p=0.049), IFNγ (p=0.033) and IL-1α (p=0.047) was evident in infertile women <35 years compared to fertile. There were no significant differences in the ≥35 years’ group. TGFα and IFNγ localised predominantly to the GE of both fertile and infertile proliferative phase endometrium.
Our data found altered proliferative phase expression of four cytokines, most notably among women <35 years with idiopathic infertility. However, gland area was unaltered suggesting that gland functionality rather than number may underlie infertility in women, with such a failure evident during the proliferative phase.