Comprehensive molecular and morphological study of abortion material in missed abortion of the first trimester

Abstract

BACKGROUND: Missed abortion is the main cause of reproductive loss in the first trimester, and genetic causes come first in the etiology of this disease. The immunological aspects of the mother-fetus system are currently widely discussed. In this regard, the study of the immunological relationship between the mother’s body and the fetus in missed abortion, depending on the chorion karyotype, as well as after suffering reproductive loss, is a topical task, as it can optimize the methods of examining patients with missed abortion and identify factors that contribute to the development of recurrent miscarriage.

AIM: The aim of this study was to investigate the morphological and immunohistochemical characteristics of abortion material in missed abortion, depending on the presence of chorionic chromosomal abnormalities and the patient’s history of reproductive losses.

MATERIALS AND METHODS: We performed a comprehensive morphological and immunohistochemical study (CD56, HLA-DR-II) of abortion material in 273 cases of missed abortion. Group 1 consisted of patients with different variants of chorionic chromosomal abnormalities (n = 169); group 2 included subjects with a normal karyotype of the chorion (n = 104). The data analysis was carried out taking into account the anamnesis of patients, depending on the presence of reproductive losses.

RESULTS: We revealed the morphological features of the abortion material in missed abortion in cases with chromosomal abnormalities of the chorion: pronounced edema, sclerosis, necrosis of chorionic villi, more pronounced inflammatory changes in the form of moderate and severe macrophage infiltration of the decidual tissue and endometrium, and accumulations of leukocytes as microabscesses. It has been proven that the severity of inflammatory changes in abortuses depends only on the chorion karyotype and does not depend on either the duration of the presence of an unviable fetal egg in the uterine cavity, or the patient’s history of reproductive losses. It was shown that the CD56 and HLA-DR-II expressions in the abortion material depend on the patient’s history of reproductive losses, regardless of the chorion karyotype.

CONCLUSIONS: In patients with an unburdened obstetric and gynecological history in the first missed abortion, it is advisable only to determine the chorion karyotype in order to identify the cause of missed abortion. The immunohistochemical study of the abortion material with the determination of the CD56 and HLA-DR-II expressions is important in repeated missed abortions, regardless of the chorion karyotype.

Keywords

missed abortion / chromosomal abnormalities of the chorion / reproductive loss / immunohistochemical study / endometrium / CD56 / HLA-DR

References

[1] Tral TG, Tolibova GK, Serdiukov SV, Polyakova VO. Morphofunctional evaluation of the causes of stilled pregnancy in the first trimester. Journal of obstetrics and women’s diseases. 2013;62(3):83–87. (In Russ.). DOI: 10.17816/JOWD62383-87

[2] Траль Т.Г., Толибова Г.Х., Сердюков С.В., Полякова В.О. Морфофункциональная оценка причин замершей беременности в первом триместре // Журнал акушерства и женских болезней. 2013. Т. 62. № 3. C. 83–87. DOI: 10.17816/JOWD62383-87

[3] Sidelnikova VM. Privychnaya poterya beremennosti. Moscow: Triada-X; 2005. (In Russ.)

[4] Сидельникова В.М. Привычная потеря беременности. Москва: Триада-Х, 2005.

[5] Bulletti C, Flamigni C, Giacomuccii E. Reproductive failure due to spontaneous abortion and recurrent miscarriage. Hum Reprod Update. 1996;2(2):118–136. DOI: 10.1093/humupd/2.2.118

[6] Bulletti C., Flamigni C., Giacomuccii E. Reproductive failure due to spontaneous abortion and recurrent miscarriage // Hum. Reprod. Update. 1996. Vol. 2. No. 2. P. 118–136. DOI: 10.1093/humupd/2.2.118

[7] Sotnikova NYu, Voronun DN, Anciferova YuS. The role of decidual CD56+ natural killers in regulation of the local immune response during early pregnancy. Journal of Ural Medical Academic Science. 2011;2–1(35):68–69. (In Russ.)

[8] Сотникова Н.Ю., Воронин Д.Н., Анциферова Ю.С. Роль децидуальных CD56+ естественных киллеров в регуляции локального иммунного ответа в ранние сроки беременности // Вестник Уральской медицинской академической науки. 2011. № 2–1 (35). С. 68–69.

[9] Kozyreva EV, Davidyan LY. Immunohistochemical features of chronic endometritis in case of infertility and miscarriage (review of literature). University proceedings. Volga region. Medical sciences. 2015:4(36):124–136. (In Russ.)

[10] Козырева Е.В., Давидян Л.Ю. Иммуногистохимические особенности хронического эндометрита при бесплодии и невынашивании беременности // Известия высших учебных заведений. Поволжский регион. Медицинские науки. 2015. № 4 (36). С. 124–136.

[11] Agnaeva AO, Bespalova ON, Sokolov DI, et al. Role of natural killer cells in reproductive failure. Journal of obstetrics and womans diseases. 2017;66(3):143–156. (In Russ.). DOI: 10.17816/jowd663143-156

[12] Агнаева А.О., Беспалова О.Н., Соколов Д.И. и др. Роль естественных киллеров (NK-клеток) в репродуктивных потерях // Журнал акушерства и женских болезней. 2017. Т. 66. № 3. С. 143–156. DOI: 10.17816/jowd663143-156

[13] Mikhailova VA, Selkov SA, Sokolov DI. Phenotypic and functional characteristics of NK cells in pregnancy. Obstetrics and Gynecology. 2011;(5):4–9. (In Russ.)

[14] Михайлова В.А., Сельков С.А., Соколов Д.И. Фенотипические и функциональные характеристики NK-клеток при беременности // Акушерство и гинекология. 2011. № 5. С. 4–9.

[15] Sharma S. Natural killer cells and regulatory T cells in early pregnancy loss. Int J Dev Biol. 2014;58(2–4):219–229. DOI: 10.1387/ijdb.140109ss

[16] Sharma S. Natural killer cells and regulatory T cells in early pregnancy loss // Int. J. Dev. Biol. 2014. Vol. 58. No. 2–4. P. 219–229. DOI: 10.1387/ijdb.140109ss

[17] Zhang X, Li J, Gu Yi, et al. A pilot study on environmental and behavioral factors related to missed abortion. Environ Health Prev Med. 2011;16(4):273–278. DOI: 10.1007/s12199-010-0196-4

[18] Zhang X., Li J., Gu Yi. et al. A pilot study on environmental and behavioral factors related to missed abortion // Environ. Health Prev. Med. 2011. Vol. 16. No. 4. P. 273–278. DOI: 10.1007/s12199-010-0196-4

[19] Mustafina LR, Khon EV, Logvinov SV, Yuriyev SYu. Cellular composition of decidua basalis infiltrate during early pregnancy in urogenital mycoplasma infection. Morphology. 2011;139(3):72–76. (In Russ.)

[20] Мустафина Л.Р., Хон Е.В., Логвинов С.В., Юрьев С.Ю. Клеточный состав инфильтрата в базальной децидуальной оболочке в ранние сроки беременности при инфицировании урогенитальными микоплазмами // Морфология. 2011. Т. 139. № 3. С. 72–76.

[21] Reinke P, Volk HD. Diagnostic and predictive value of an immune monitoring program for complications after kidney transplantation. Urol Int. 1992;49(2):69–75. DOI: 10.1159/000282398.

[22] Reinke P., Volk H.D. Diagnostic and predictive value of an immune monitoring program for complications after kidney transplantation // Urol. Int. 1992. Vol. 49. No. 2. P. 69–75. DOI: 10.1159/000282398

[23] Reinke P, Fietze E, Docke WD, et al. Late acute rejection in long-term renal allograft recipients. Diagnostic and predictive value of circulating activated T cells. Transplantation. 1994;58(1):35–41.

[24] Reinke P., Fietze E., Docke W.D. et al. Late acute rejection in long-term renal allograft recipients. Diagnostic and predictive value of circulating activated T cells // Transplantation. 1994. Vol. 58. No. 1. P. 35–41.

[25] Henny FC, Weening JJ, Baldwin WM, et al. Expression of HLA-DR antigens on peripheral blood T lymphocytes and renal graft tubular epithelial cells in association with rejection. Transplantation. 1986;42(5):479–483. DOI: 10.1097/00007890-198611000-00007

[26] Henny F.C., Weening J.J., Baldwin W.M. et al. Expression of HLA-DR antigens on peripheral blood T lymphocytes and renal graft tubular epithelial cells in association with rejection // Transplantation. 1986. Vol. 42. No. 5. P. 479–483. DOI: 10.1097/00007890-198611000-00007

[27] Loewendorf AI, Nguyen TA, Yesayan MN, et al. Normal human pregnancy results in Maternal Immune Activation in the Periphery and at the Uteroplacental Interface. PLoS One. 2014;9(5):e96723. DOI: 10.1371/journal.pone.0096723

[28] Loewendorf A.I., Nguyen T.A., Yesayan M.N. et al. Normal human pregnancy results in maternal immune activation in the periphery and at the uteroplacental interface // PLoS One. 2014. Vol. 9. No. 5. P. e96723. DOI: 10.1371/journal.pone.0096723

[29] Ellinidi VN, Davydova NI, Kalinina NM, et al. Modern opportunities for diagnostics of chronic endometritis. Journal of obstetrics and womans diseases. 2003;52(3):64–68. (In Russ.)

[30] Эллиниди В.Н., Давыдова Н.И., Калинина Н.М. и др. Современные возможности диагностики хронического эндометрита // Журнал акушерства и женских болезней. 2003. Т. 52. № 3. С. 64–68.

[31] Demidova EM. Privychnyj vykidysh (patogenez, akusherskaja taktika) [dissertation] Moscow; 1993. (In Russ.). [cited 16 Aug 2021.] Available from: http://medical-diss.com/docreader/405801/a?#?page=1

[32] Демидова Е.М. Привычный выкидыш (патогенез, акушерская тактика): дис. ... д-ра мед. наук. Москва, 1993. [дата обращения 16.08.2021]. Доступ по ссылке: http://medical-diss.com/docreader/405801/a?#?page=1

[33] Akulich NS, Runets UF, Yudina OA, Sheviako AD. Morphological criteria for miscarriage of early pregnancy. Medical Journal. 2017;3(61):49–52. (In Russ.)

[34] Акулич Н.С., Рунец У.Ф., Юдина О.А., Шевяко А.Д. Морфологические критерии невынашивания беременности ранних сроков // Медицинский журнал. 2017. № 3 (61). С. 49–52.

[35] Khelnitsky OK. Tsitologicheskaya i gistologicheskaya diagnostika zabolevaniy sheyki i tela matki. St. Petersburg: SOTIS; 1999. (In Russ.)

[36] Хмельницкий О.К. Цитологическая и гистологическая диагностика заболеваний шейки и тела матки. Санкт-Петербург: СОТИС, 1999.

[37] Peretyatko LP, Fateeva NV, Kuznetsov RA, Malyshkina AI. The comparative morphology of the villous chorion at 5−12 week pregnancy at the chronic endometritis complicated by habitual miscarriage and artificial abortions. Tavricheskiy Mediko-Biologicheskiy Vestnik. 2017;20(2–2):98–103. (In Russ.)

[38] Перетятко Л.П., Фатеева Н.В., Кузнецов Р.А., Малышкина А.И. Сравнительная морфология ворсинчатого хориона 5–12 недель беременности при хроническом эндометрите, осложненном привычным невынашиванием, и артифициальных абортах // Таврический медико-биологический вестник. 2017. Т. 20. № 2–2. С. 98–103.

[39] Zakharov GA, Galiulina EV, Zarechnova NN. Structure of ovum of abortive material of human embryos with non-viable pregnancy with sexually transmitted diseases. Tambov University Reports. Series Natural and Technical Sciences. 2014:19(6):2001–2003. (In Russ.)

[40] Захаров Г.А., Галиулина Е.В., Заречнова Н.Н. Строение плодного яйца абортивного материала эмбрионов человека при замершей беременности на фоне болезней, передающихся половым путем // Вестник Тамбовского университета. Серия: Естественные и технические науки. 2014. Т. 19. № 6. С. 2001–2003.

RIGHTS & PERMISSIONS

Eсо-Vector