Differential apoptotic activity in trophoblast of spontaneous abortions and normal pregnancies
Abstract
Introduction. Apoptosis is a key process during normal trophoblastic development and, consequently, the whole gestation. However, in trophoblastic differentiation in spontaneous abortions apoptosis has been hardly investigated. Therefore, the aim of the study was to investigate the correlation between apoptotic frequency in trophoblast and spontaneous abortion incidences.
Material and methods. A total of 72 trophoblastic tissue samples were immunohistochemically examined. 42 of 72 derived from first-trimester spontaneous abortions and the remaining 30 from elective terminations during the same trimester of pregnancy. TUNEL assay and M30 marker were used for apoptosis evaluation by immunohistochemistry.
Results. Comparative study of tissues from spontaneous abortions and elective pregnancy terminations demonstrated increased expression of both apoptotic markers in tissues derived from spontaneous abortions compared to normal pregnancies. In addition, statistical analysis correlated maternal age and gravidity with increased spontaneous abortion incidences. Moreover, both M30 and TUNEL staining were significantly correlated with maternal age and primigravidity in spontaneous abortion cases.
Conclusions. Our data proved that elevated apoptotic activity during the first pregnancy trimester is clearly involved in spontaneous abortions. Moreover, two well-established apoptotic markers revealed high statistical significance in the evaluation of post-abortive tissues.
Keywords: spontaneous abortiontrophoblastapoptosisTUNEL assayM30 markerIHC
References
- du Fossé NA, van der Hoorn MLP, van Lith JMM, et al. Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Hum Reprod Update. 2020; 26(5): 650–669.
- Volgsten H, Jansson C, Darj E, et al. Women's experiences of miscarriage related to diagnosis, duration, and type of treatment. Acta Obstet Gynecol Scand. 2018; 97(12): 1491–1498.
- Hardy K, Hardy PJ, Jacobs PA, et al. Temporal changes in chromosome abnormalities in human spontaneous abortions: Results of 40 years of analysis. Am J Med Genet A. 2016; 170(10): 2671–2680.
- Fang Y, Feng X, Xue N, et al. STAT3 signaling pathway is involved in the pathogenesis of miscarriage. Placenta. 2020; 101: 30–38.
- Atia TA. Placental apoptosis in recurrent miscarriage. Kaohsiung J Med Sci. 2017; 33(9): 449–452.
- Xiao Q, Zeng FL, Tang GY, et al. Expression of galectin-3 and apoptosis in placental villi from patients with missed abortion during early pregnancy. Exp Ther Med. 2019; 17(4): 2623–2631.
- Boeddeker SJ, Hess AP. The role of apoptosis in human embryo implantation. J Reprod Immunol. 2015; 108: 114–122.
- Ding J, Yin T, Yan N, et al. FasL on decidual macrophages mediates trophoblast apoptosis: A potential cause of recurrent miscarriage. Int J Mol Med. 2019; 43(6): 2376–2386.
- Longtine MS, Chen B, Odibo AO, et al. Caspase-mediated apoptosis of trophoblasts in term human placental villi is restricted to cytotrophoblasts and absent from the multinucleated syncytiotrophoblast. Reproduction. 2012; 143(1): 107–121.
- Burton GJ, Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol. 2018; 218(2S): S745–S761.
- Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992; 119(3): 493–501.
- Kadyrov M, Kaufmann P, Huppertz B. Expression of a cytokeratin 18 neo-epitope is a specific marker for trophoblast apoptosis in human placenta. Placenta. 2001; 22(1): 44–48.
- Xu L, Mao Xy, Fan Cf, et al. MTA1 expression correlates significantly with cigarette smoke in non-small cell lung cancer. Virchows Arch. 2011; 459(4): 415–422.
- Mekinian A, Cohen J, Alijotas-Reig J, et al. Unexplained Recurrent Miscarriage and Recurrent Implantation Failure: Is There a Place for Immunomodulation? Am J Reprod Immunol. 2016; 76(1): 8–28.
- Lv X, Cai Z, Li Su. Increased apoptosis rate of human decidual cells and cytotrophoblasts in patients with recurrent spontaneous abortion as a result of abnormal expression of CDKN1A and Bax. Exp Ther Med. 2016; 12(5): 2865–2868.
- Mayhew TM. Turnover of human villous trophoblast in normal pregnancy: what do we know and what do we need to know? Placenta. 2014; 35(4): 229–240.
- Peng YB, Liu H, Huang SH, et al. and Ouyang X. The study of the relationship between aberrant expression of hot shock protein 70 (HSP70) and spontaneous abortion. Eur Rev Med Pharmacol Sci. 2017; 21: 652–656.
- Sun, Q and Zhang X.L. Research on apoptotic signalling pathways of recurrent spontaneous abortion caused by dysfunction of trophoblast infiltration. Eur Rev Med Pharmacol Sci. 2017; 21: 12–19.
- Gurevich P, Elhayany A, Milovanov AP, et al. The placental barrier in allogenic immune conflict in spontaneous early abortions: immunohistochemical and morphological study. Am J Reprod Immunol. 2007; 58(5): 460–467.
- Männistö J, Mentula M, Bloigu A, et al. Medical termination of pregnancy during the second versus the first trimester and its effects on subsequent pregnancy. Contraception. 2014; 89(2): 109–115.
- Linnakaari R, Helle N, Mentula M, et al. Trends in the incidence, rate and treatment of miscarriage-nationwide register-study in Finland, 1998-2016. Hum Reprod. 2019; 34(11): 2120–2128.
- Zhou H, Liu Y, Liu Lu, et al. Maternal pre-pregnancy risk factors for miscarriage from a prevention perspective: a cohort study in China. Eur J Obstet Gynecol Reprod Biol. 2016; 206: 57–63.
- Wu F, Tian F, Zeng W, et al. Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis. Cell Death Dis. 2017; 8(6): e2908.
- Sharma M, Kumar R, Bhatla N, et al. A comparative study of apoptosis in placentas of normal and preeclamptic Indian pregnant women by TUNEL assay and M30 immunostaining. J Clin Lab Anal. 2012; 26(6): 459–466.
- Raguema N, Moustadraf S, Bertagnolli M. Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia. Front Physiol. 2020; 11: 98.
- Redman CWG, Staff AC, Roberts JM. Syncytiotrophoblast stress in preeclampsia: the convergence point for multiple pathways. Am J Obstet Gynecol. 2020 [Epub ahead of print].
- Kasture V, Sahay A, Joshi S. Cell death mechanisms and their roles in pregnancy related disorders. Adv Protein Chem Struct Biol. 2021; 126: 195–225.
