Introduction
Preterm delivery is a persisting problem of modern neonatal medicine.
Despite the continued development of neonatal support, due to the
frequent occurrence of preterm birth (PTB), neonatal outcomes are still
unsatisfactory1. PTB occurs in 5-9% in Europe,
12-14% in the United States, and around 18% in Africa and
Asia2; it leads to critical medical conditions of the
fetuses, the psychological distress of the parents, and significant
economic losses as each of these newborns require exceptional medical
support.
Preterm babies are vulnerable because of the high incidence of
respiratory distress (93% of infants), retinopathy of prematurity
(59%), patent ductus arteriosus (46%), bronchopulmonary dysplasia
(42%), late-onset sepsis (36%), necrotizing enterocolitis (11%),
grade III or higher (7-9%) intraventricular hemorrhage, periventricular
leukomalacia (3%), according to a report from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
Neonatal Research Network on very low birth weight (less than 1500
g)3.
There are several hypotheses on why PTB occurs. The factors which seem
to play a role include preterm hypothalamic–pituitary–adrenal axis
stimulation connected with a stress reaction, preterm placental
abruption, pathological uterine expansion, and resulting preterm rupture
of the membranes, as well as an inflammatory response in the urogenital
tract4,5.
The inflammatory effect is one of the mechanisms of PTB and term
delivery. A higher concentration of the inflammatory cytokines was found
in the amniotic fluid after delivery6,7. Raba et al.,
in their study, observed that inflammatory cytokines played a crucial
role in over 80% of PTB cases, especially in deliveries before 30.
hbd8. Preterm prelabour rupture of the membranes might
also be caused by an infection of the amniotic sac. Vagina’s bacterial
flora plays an important role, as the presence of Ureaplasma
urealyticum, Mycoplasma hominis, and Chlamydia trachomatis predisposes
to PTB9,10.
The endocannabinoid signaling system (ECS) includes the endocannabinoid
receptor type 1 (CB1) and type 2 (CB2) as well as endogenous ligand
(arachidonoylethanolamide and 2-arachidonoyl glycerol) for the
cannabinoid receptors11. Low levels of anandamide help
support the pregnancy, however, if its level becomes too high, it can
lead to miscarriages12. One of the best-known
exogenous activators of CB1 and CB2 is Δ9-tetrahydrocannabinol (THC),
found in Cannabis sativa (marijuana), which is often used as a
psychoactive agent13. Signaling pathways mediated by
the cannabinoid receptors (CB) may affect cell proliferation,
differentiation, and apoptosis in animal and human
cells14,15.
CB1 is encoded by the CNR1 gene and is found mainly in the
central nervous system and the heart, liver, uterus, testes, and the
small intestine16,17. CB1 receptor also has
alternative splice variant forms - endocannabinoid receptor type 1a
(CB1a) and endocannabinoid receptor type 1b (CB1b). Both isoforms are
encoded by the gene CNR1 and are found in the brain, similarly to
CB118,19. The CB2, encoded by CNR2 is expressed
in T and B lymphocytes as well as macrophages and hematopoietic cells,
brain, and other peripheral tissues, where it modulates the immune
response16,17 .
CB is involved in both male and female reproductive
systems13. In the female reproductive system, the CB
receptors are located in the oviduct, uterus,
embryo14. ECS plays a significant role in oogenesis
regulation, embryo development, embryo transport, implantation, and
placental development. ECS is also involved in the maintenance of
pregnancy and in childbirth14. Many studies show that
the ECS affects pregnancy outcomes, but the precise role of the
endocannabinoid receptor is still unknown.
The objective of the study was the investigation of the relationship
between the expression of the cannabinoid receptors within the placenta
after delivery and the problem of preterm delivery.