Decreased expression of Placental Cannabinoid Receptor Expression indicator in predicting Preterm Birth: Study
Preterm birth (PTB) continues to pose a challenge in neonatal medicine, and it is the major cause of perinatal morbidity and mortality. Despite modern advances in obstetric and perinatal care, neonatal outcomes are still unsatisfactory due to high PTB rates. The etiology of PTB is complex and multifactorial. Key mechanisms leading to PTB include the early activation of the fetal hypothalamic–pituitary–adrenal axis in response to maternal and/or fetal stress, premature placental abruption, uterine expansion problems, cervical insufficiency, and inflammation, especially in the urogenital tract. Preterm prelabor rupture of the membranes (PPROM) also contributes to a high incidence of PTB. PPROM is mainly triggered by inflammation associated with an infection, where inflammatory cytokines weaken the fetal membranes.
Inflammation is a crucial factor in both PTB and term birth. Although a higher concentration of inflammatory cytokines was found in the amniotic fluid following delivery. The endocannabinoid signaling system (ECS) includes the cannabinoid receptor (CBR) type 1 (CBR1) and type 2 (CBR2), along with their endogenous ligands (arachidonoylethanolamide and 2-arachidonoyl glycerol) for the CBRs. THC (Δ9-tetrahydrocannabinol) is one of the best-known exogenous activators of the CBR1 and CBR2. It is found in Cannabis sativa (marijuana), widely recognised as a psychoactive agent. Signaling pathways mediated by the CBR may affect cell proliferation, differentiation, and apoptosis in animal and human cells CBRs are involved in both the male and female reproductive systems (the oviduct, uterus, and embryo). The ECS plays a significant role in the regulation of oogenesis, embryo development, embryo transport, implantation, and placental development, as well as pregnancy and childbirth. ECS dysregulation might contribute to delayed embryonic development, poor blastocyst implantation, inhibited decidualization, compromised placentation, preeclampsia, ectopic pregnancy, and miscarriage. While many studies showed that the ECS affected pregnancy outcomes, the precise role of the CBR is yet to be fully understood.
The cannabinoid receptor (CBR) plays a significant role in oogenesis, pregnancy, and childbirth. It might also play a significant role in preterm birth (PTB). The aim of the study was to investigate the association between the expression of the CBR in the placenta and the incidence of PTB.
This prospective, observational, multicentre preliminary study was conducted on placental samples obtained from 109 women. The study included 95 patients hospitalized due to the high risk of PTB. They were divided into two groups: Group 1, where the expression of the CBR1 and CBR1a was analyzed, and Group 2, in which we examined CBR2 expression. The control group, that is, Group 3, consisted of 14 women who delivered at term, and their placentas were tested for the presence of all three receptor types (CBR1, CBR1a, and CBR2).
The study used reverse transcription and real-time PCR methods to assess the expression of CBRs in the placental tissues. The expression of the CBR2, CBR1, and CBR1a receptors was significantly lower in the placentas of women after PTB compared to those after term births, p = 0 038, 0.033, and 0.034, respectively.
In this study, authors established a positive correlation between the expression of the CBR in the analyzed postpartum human placental tissues and PTB. First of all, they confirmed that CBRs were present in the placental tissue after delivery. Moreover, we demonstrated a significant decrease in the expressions of the CBR1, CBR1a, and CBR2 in the placentas obtained from women after preterm deliveries, compared to placentas from women after term deliveries, suggesting a potential role of the receptors in the mechanisms leading to PTB. Last but not least, a negative correlation occurred between pregnancy duration and the CBR2, perhaps due to the two main effects of CBRs, that is, their impact on muscle tissue and their role in inflammatory processes.
The present research revealed a significant decrease in the expression of the CBR1, CBR1a, and CBR2 in the placentas following PTB, in contrast to term births. These findings hold profound implications for clinical practice, indicating the potential for developing a new biomarker profile using CBR expression levels for PTB prediction. An innovative estimation technology has the potential to greatly transform prenatal care. It could help healthcare personnel detect high-risk pregnancies and take appropriate actions, ultimately improving neonatal outcomes.
The ethical considerations surrounding the measurement of CBR expression in the placental tissue throughout pregnancy necessitate careful examination. However, the insights gained provide a compelling rationale for further research. There is a pressing need for additional studies aimed at developing noninvasive or minimally invasive techniques for evaluating CBR expression that could be implemented in clinical settings.
The expression of CBRs in the placenta shows promise as a reliable marker of the risk of PTB. This highlights the significance of the ECS in pregnancy and childbirth. Our findings contribute to the growing body of research on prenatal biomarkers, introducing a possible new area of study that has the potential to enhance prenatal diagnosis and therapies. Therefore, further studies are needed to assess the expression of the CBR during pregnancy.
Source: Stepan Feduniw, Izabela Krupa, Katarzyna Łagowska; Hindawi Journal of Pregnancy Volume 2024, Article ID 6620156, 10 pages https://doi.org/10.1155/2024/6620156
