“Relaxin-dependent” way of implementing spontaneous preterm labor in multiple pregnancies: The involvement of placental relaxin 2

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Abstract

BACKGROUND: Despite numerous studies, the etiopathogenesis of preterm birth in multiple pregnancy remains unclear, which determines the low effectiveness of measures for the prevention of preterm birth. This fact makes it necessary to study possible ways of implementing preterm birth in multiple pregnancies and to search for new biomarkers of their pathogenetic links. Experimental and clinical studies have demonstrated the contribution of the pleiotropic hormone relaxin to the regulation of a wide range of physiological processes and its role in the implementation of the pathogenetic mechanisms of pregnancy complications, primarily premature birth. The proven autocrine / paracrine mechanism of placental relaxin action, which implements important local effects, determines the prospects for studying the contribution of its dysregulation to the implementation of spontaneous preterm labor in multiple pregnancies.

MATERIALS AND METHODS: A morphological examination of 92 placentas from 46 deliveries of dichorionic diamniotic twins was performed: 24 of them were spontaneous premature births and 22 spontaneous term births. Histological examination of placentas along with immunohistochemical verification of relaxin 2 expression in the chorionic villus of the dichorial twins’ placentas were carried out.

RESULTS: Histological examination of the dichorionic twins’ placentas revealed that those from spontaneous preterm birth were characterized by a higher frequency of chronic placental insufficiency with reduced compensatory and adaptive mechanisms and more pronounced circulatory disorders in the circulatory bed of the villous tree, when compared to placentas from spontaneous term labor. The first verification of relaxin 2 expression in the chorionic villi of the dichorionic twins’ placenta showed the role of the peptide in the initiation of spontaneous preterm birth. The relative area of relaxin 2 expression in spontaneous preterm labor was significantly higher (p < 0.05) compared to that in spontaneous term labor.

CONCLUSIONS: The data obtained confirm the hypothesis put forward about the involvement of placental relaxin in the pathogenesis of spontaneous preterm labor in multiple pregnancies. The authors were the first to propose the definition of a “relaxin-dependent” way of implementing spontaneous preterm labor. To help define new preventive strategies, the prospects for further studies of the role and significance of relaxin in the implementation of pathogenic processes involved in spontaneous preterm birth in multiple pregnancies have been outlined.

About the authors

Olga V. Pachuliya

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Author for correspondence.
Email: for.olga.kosyakova@gmail.com
ORCID iD: 0000-0003-4116-0222
SPIN-code: 1204-3160

MD

Russian Federation, 3 Mendeleevskaya line, Saint Petersburg, 199034

Olesya N. Bespalova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953

MD, PhD, DSci (Medicine)

Russian Federation, 3 Mendeleevskaya line, Saint Petersburg, 199034

Mariya G. Butenko

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: butenkomariabutenko@gmail.com
ORCID iD: 0000-0002-1404-371X

MD

Russian Federation, 3 Mendeleevskaya line, Saint Petersburg, 199034

Yulia P. Milyutina

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: milyutina1010@mail.ru
ORCID iD: 0000-0003-1951-8312

MD, PhD

Russian Federation, 3 Mendeleevskaya line, Saint Petersburg, 199034

Tatyana G. Tral

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: ttg.tral@yandex.ru
ORCID iD: 0000-0001-8948-4811
SPIN-code: 1244-9631
Scopus Author ID: 37666260400

MD, PhD

Russian Federation, 3 Mendeleevskaya line, Saint Petersburg, 199034

Gulrukhsor Kh. Tolibova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: gulyatolibova@yandex.ru
ORCID iD: 0000-0002-6216-6220
SPIN-code: 7544-4825
Scopus Author ID: 23111355700
ResearcherId: Y-6671-2018

MD, PhD, DSci (Medicine)

Russian Federation, 3 Mendeleevskaya line, Saint Petersburg, 199034

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Pathological processes that potentially occur in preterm delivery by influencing autocrine/paracrine hormonal regulation ([21], as amended)

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3. Fig. 2. Expression area of relaxin-2. *p < 0.05

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4. Fig. 3. Expression of relaxin-2 in the villous chorion of the placenta of dichorionic twins: a — in spontaneous preterm delivery; b — in delivery at term. Immunohistochemical staining, 400×

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