Studying the HIF-1 alpha molecule in endometrial samples of patients with missed abortion and medical abortion

Objective: The aim is to explain the role of the HIF-1 alpha molecule in the pathology of missed abortion and to elucidate the relationship between cellular aging and missed abortion. This study seeks to uncover the mechanisms behind the still-unknown etiology of missed abortion. Identifying the molecules and pathways involved in the etiology of missed abortion could provide new insights for predicting missed abortion and developing prophylactic treatments, thus offering new horizons for the medical field. Materials and Methods: Pregnant women diagnosed with missed abortion between 10 and 20 weeks of gestation, as well as those who underwent medical interventions resulting in fetal loss but with positive fetal heartbeat, were included in our study after obtaining necessary information and ethical consent forms. Endometrial tissues from the aborted materials and placenta obtained post-abortion from both patient groups were washed with 0.9% NaCl to separate blood from the tissues before placing them in solutions, and to preserve the tissue morphology. The tissues were then divided and analyzed using immunohistochemical staining method. The staining levels of HIF-1 alpha, HTRA-1, P16 INK4a, NF-kB, and the HES molecular family in the cells of the tissues were calculated using the H-Score technique and compared. Results: In our study, the average age of 20 patients (ranging from 21 to 44 years old) diagnosed with missed abortion and hospitalized between 10 and 20 weeks of gestation in the Department of Obstetrics and Gynecology at Celal Bayar University was calculated as 31.95 years. The average age of 17 patients (ranging from 23 to 41 years old) who underwent medical abortion and were included in the control group from the same department was 33.88 years. Among the patients in the missed abortion group, 9 were nulliparous, while in the induced abortion group, 2 were nulliparous and the rest were multiparous. There was no statistically significant difference between the two groups in terms of obstetric history. In both groups, villous and stromal cell populations of the endometrium were evaluated separately using immunohistochemical methods. In the missed abortion group, high immunoreactivity of the molecules we investigated HIF-1 alpha, the HES molecular family, HTRA-1, P16 INK4a, and NF-kB was observed in all decidual cell samples and in placental syncytiotrophoblast and cytotrophoblast cells. Conversely, in the control group, the immunoreactivity of all antibodies in both stromal and villous cells was found to be low. Statistical comparisons between the two groups using appropriate methods showed that the difference was statistically significant (p < 0.05). Conclusion: There are many unresolved aspects in the pathophysiology of missed abortion, and various mechanisms contribute to its occurrence. Hypoxia and cellular senescence also play a role in this pathology. Our study demonstrates that the establishment of an appropriate microenvironment is crucial for a healthy pregnancy. Imbalances in hypoxia, cellular senescence, proliferation, and apoptosis may lead to missed abortion. Notably, HIF-1 alpha and other molecules associated with it, which are also involved in cellular senescence, were found to be significantly increased in the missed abortion group. Understanding these mechanisms may provide valuable insights into the approach, prediction, and development of treatments for missed abortion, thereby offering a broader perspective. Key Words: Missed Abortion, Hif-1 Alpha, Hes Molecule Family, Htra, Nf-Kb, P16-Ink4a''