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ORIGINAL PAPER
The effects of delta-opioid receptor agonist on the expression of genes encoding chosen cytokines and chemokines in endometrium of early pregnant pigs
1
University of Warmia and Mazury in Olsztyn, Faculty of Biology and Biotechnology,
Department of Animal Anatomy and Physiology, 10-719 Olsztyn, Poland
2
Polish Academy of Sciences, InLife Institute of Animal Reproduction and Food Research, 10-683 Olsztyn, Poland
Publication date: 2026-06-19
Corresponding author
A. Zmijewska
University of Warmia and Mazury in Olsztyn, Faculty of Biology and Biotechnology, Department of Animal Anatomy and Physiology, 10-719 Olsztyn, Poland
University of Warmia and Mazury in Olsztyn, Faculty of Biology and Biotechnology, Department of Animal Anatomy and Physiology, 10-719 Olsztyn, Poland
KEYWORDS
TOPICS
ABSTRACT
Endogenous opioid peptides (EOPs) are widely distributed
in reproductive tissues and are involved in the regulation of uterine function,
including immunological and endocrine processes essential for early pregnancy.
Among opioid systems, enkephalins, acting via the delta-opioid receptor (δ), are
considered important modulators of immune responses. This study investigated
the effects of δ-opioid receptor activation on the expression of selected
cytokines, chemokines, and their receptors, as well as genes associated with
endometrial function in the porcine uterus during early pregnancy. Endometrial
explants were collected on days 12–13 (maternal recognition of pregnancy) and
15–16 (onset of implantation) of pregnancy and incubated in vitro for 6 h with
a δ-opioid receptor agonist (DPLPE) at concentrations of 10−9–10−7 M. Gene
expression was analysed using quantitative real-time PCR. Treatment with
DPLPE at 10−9 M significantly increased mRNA expression of pro-inflammatory
cytokines IL1β and IL6 during both studied periods, and IL15 and IL18 during
implantation. The same dose also upregulated chemokines CXCL10, CXCL11,
and XCL1, as well as the chemokine receptors CXCR3 and CXCR4, in a perioddependent
manner. In addition, DPLPE affected the expression of genes related
to endometrial activity, including ESR1, PAQR9, TLR4, MAP2K2, CLDND1, and
DNMT1, while no effects were observed for CDK1, PDCD10, or TGFα. These
results demonstrate that δ-opioid receptor activation influences gene expression
associated with immune and endometrial functions in porcine endometrium,
supporting a role of the opioid system in regulating the uterine environment
during early pregnancy.
FUNDING
The study was funded by the UWM grant
No. 12.610.005.110.
CONFLICT OF INTEREST
The Authors declare that there is no conflict of interest.
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