Cycle-Dependent Expression of Immune, Morphogenetic, Apoptotic, and Steroid-Related Markers in the Endometrium of Infertile Women: A Pilot Study

Infertility affects a substantial proportion of women of reproductive age and is frequently associated with impaired endometrial receptivity. Successful implantation depends on tightly regulated hormonal, immune, apoptotic, and stress-response pathways within the endometrium. This pilot study aimed to evaluate the expression and distribution of granulocyte colony-stimulating factor (G-CSF), bone morphogenetic proteins 2/4 (BMP-2/4), heat shock protein 70 (HSP-70), apoptosis, progesterone, estrogen, and pentraxin-3 (PTX-3) in the endometrium of infertile women across different menstrual cycle days. A descriptive cross-sectional analysis was performed on endometrial tissue samples obtained from six infertile women aged 21–49 years at various menstrual cycle days. Routine histology, immunohistochemistry, TUNEL assay, and chromogenic in situ hybridization were
used to assess tissue morphology, protein expression, apoptotic activity, and PTX-3 gene expression. Quantitative evaluation was applied to immunohistochemical markers and apoptosis, while PTX-3 expression was assessed semi-quantitatively. G-CSF expression showed low-to-moderate levels with a relative mid-cycle increase. BMP-2/4 demonstrated the highest overall positivity across most cycle days, with marked inter-sample variability. HSP-70 exhibited pronounced cycle-dependent variability. Apoptotic activity increased toward mid-to-late cycle days. Progesterone and estrogen positivity was heterogeneous and limited to selected cycle days. PTX-3 gene expression was highest during mid-cycle days and decreased toward later phases. No clear association with patient age was observed.
Conclusions: The findings indicate distinct and cycle-dependent patterns of immune, morphogenetic, apoptotic, hormonal, and inflammatory markers in the endometrium of infertile women. These results highlight the dynamic nature of endometrial regulation and suggest that altered temporal coordination of these pathways may contribute to impaired endometrial receptivity.