Expression of the orexin system in the porcine uterus, conceptus and trophoblast during early pregnancy

Abstract

Orexin A and B are hypothalamic peptides derived from the prepro-orexin (PPO) precursor. Orexins stimulate food intake and arousal. Those peptides bind and activate two G protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Numerous authors have suggested that orexins play an important role in the regulation of the reproductive functions. The objective of the present study was to analyse the presence of and changes in the gene and protein expression pattern of the orexin system in the porcine uterus, conceptus and trophoblast (chorioallantois) during early pregnancy. In the endometrium, the highest PPO and OX1R gene expression was detected on days 15 to 16 of gestation. The OX2R mRNA content in the endometrium was higher on days 10 to 11 and 15 to 16 than on days 12 to 13 and 27 to 28. In the trophoblasts, PPO gene expression was higher on days 30 to 32 than on days 27 to 28. The highest PPO protein content in the endometrium was noted on days 12 to 13. The highest OX1R protein content in the endometrium was detected on days 10 to 11, whereas OX2R protein on days 15 to 16. In the trophoblasts, PPO and OX1R protein levels were more pronounced on days 27 to 28 than on days 30 to 32, but OX2R expression was higher on days 30 to 32. The expression of PPO, OX1R and OX2R was different in the conceptuses and trophoblasts during early pregnancy. Local orexin production and the presence of the specific orexin receptors suggest that the orexin system may participate in the control of porcine reproductive functions by exerting endocrine and auto/paracrine effects on the uterus, conceptuses and trophoblasts during early pregnancy. This study provides the first evidence for the presence of orexins and their receptors in the uteri, conceptuses and trophoblasts in pigs during early pregnancy. The local orexin system is dependent on the stage of pregnancy.Keywords: orexin A and B, orexin receptors 1 and 2, uterus, pregnancy, pig ImplicationsThere is a growing body of evidence to implicate the existence of a common endocrine system that controls metabolism and the reproductive system. Orexin A and orexin B, the hormones that control energy homoeostasis, may be a part of the above system. This paper provides the pioneering information about the presence of orexins and orexin receptors in the porcine uterus, conceptus and trophoblast during early pregnancy, the crucial period for reproductive success. The expression levels of orexins and their receptors were found to be correlated with the stages of early pregnancy. A sound knowledge of mechanisms that control energy homoeostasis and reproduction is needed in animal breeding practice.

The in vitro effect of progesterone on the orexin system in porcine uterine tissues during early pregnancy

“…The expression of the PPO gene, OXA and OXB proteins and OX1R and OX2R genes and proteins in the uterus during the oestrous cycle and early pregnancy has been previously reported [ 13 , 14 ]. The orexin system has been localised in the porcine uterus, however, there is a general scarcity of data describing the relationship between orexins and the factors regulating reproductive function, including steroid hormones and prostaglandins.…”

“…Orexins participate in the regulation of reproductive function by influencing the hypothalamic-pituitary-ovarian axis. Our previous findings [ 13 , 14 ] indicate that the orexin system is expressed in the porcine uterus and is dependent on the local hormonal milieu. Progesterone could be responsible for the local regulation of orexin activity during pregnancy.…”

“…The elements of the orexin system have been observed in feline, canine and human placenta [ 11 , 12 ]. The expression of orexin system genes and proteins was also confirmed in the porcine uterus, conceptus and trophoblasts [ 13 , 14 ]. Our previous research demonstrated changes in the endometrial and myometrial expression of orexin and orexin receptor genes and proteins during the oestrous cycle and early pregnancy, which indicates that orexin expression could be dependent on the local hormonal status, including the presence and concentration of steroid hormones [ 7 , 13 , 14 ].…”

The effect of orexin B on steroidogenic acute regulatory protein, P450 side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase gene expression, and progesterone and androstenedione secretion by the porcine uterus during early pregnancy and the estrous cycle1

“…However, the role of orexins in the uterus has not been fully elucidated to date. Smolinska et al (2015) observed the expression of PPO, OX1R, OX2R genes and OXA, OXB, OX1R, OX2R proteins in the porcine endometrium, myometrium, conceptus, and trophoblast in the early stages of gestation. Orexin A was also found in human, canine, and feline placenta (Nakabayashi et al, 2003;Dall'Aglio et al, 2012, whereas OX1R was localized in the syncytiotrophoblast and decidual cells of feline placenta and OX2R was identified in human endometrial glands (Dall'Aglio et al, 2012).…”

Impact of negative energy balance on transcriptomic profiles of three endometrial cell types isolated by laser capture microdissection in postpartum dairy cows

“…In addition, LE cells differentiate from GE by the expression of genes like CYP26A1, that encodes a key enzyme of trans retinoic acid inactivation, already shown as strongly expressed in luminal epithelial cells of rat endometrium and playing a role in embryo implantation [44]. Endometrial expression of HCTR1 has been reported to be, with its main ligand orexin-A, an important local regulator of endometrial functions in porcine uterus [45,46].…”