The regulation of oxytocin and oxytocin receptor in human placenta according to gestational age

Abstract

Oxytocin (OXT) is a peptide hormone that plays a central role in the regulation of parturition and lactation. OXT signaling is mediated by OXT receptor (OXTR), which shows species- and tissue-specific expressions and gene regulation. In the present study, we examined the synthesis of OXT and OXTR in human placenta tissue according to gestational age. A total of 48 placentas were divided into early preterm, late preterm and term groups depending on gestational age, and expression of OXT and OXTR was evaluated. First, OXT and OXTR mRNA and protein were detected in normal placenta tissue via Q-PCR, Dot-blot and Western blot assay. Both OXT and OXTR levels in normal placenta increased gradually in the late stage of pregnancy, suggesting that local OXT may play a critical role in the function of the placenta. To determine the regulatory mechanism of OXT, placental BeWo cells were administrated estrogen (E2) or progesterone (P), and expression of OXT and OXTR was tested. The mRNA and protein levels of OXT and OXTR were upregulated by E2 but blocked by co-treatment with P In order to confirm the estrogen receptor (ESR)-mediated signaling, we administrated ESR antagonists together with E2 to BeWo cells. As a result, both OXT and OXTR were significantly altered by ESR1 antagonist (MPP) while moderately regulated by ESR2 antagonist (PHTPP). These results suggest that OXT and OXTR are controlled mainly by E2 in the placenta via ESR1 and thus may play physiological functions in the human placenta during the late stage of pregnancy.

Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease

“…Abnormal placental cytokine–cytokine receptor interaction further hints at heightened immunological response resulting from PNS. Next, abnormalities in the placental Oxt signaling pathway, which is thought to play a critical role in placental function [77] , may in addition be linked to the low levels in Oxt gene expression observed in the stressed fetal and adult hypothalamus. The observed circadian entrainment in PNS placentas, including abnormally high levels of the Period (Per) canonical clock genes, hints at alterations in placental rhythmicity, which is independent from the mother and the fetus [78] .…”

The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation

“…Indeed, a greater rise in circulating oxytocin concentrations from early to late pregnancy in pregnant women, is associated with a stronger bond between a mother and her infant (Levine et al, 2007 ). Concurrently, placental expression of oxytocin also peaks at term in humans (Kim S. C. et al, 2017 ). The rat placenta also produces oxytocin (Lefebvre et al, 1992 ), while placental expression in other species remains unclear.…”

Maternal care boosted by paternal imprinting in mammals

“…Together, these data strongly suggest that placental lactogens have a direct effect on maternal care behaviour. The neurotransmitter serotonin, important in maternal care [ 27 ], is manufactured by the placenta, although thought to be directed at the foetal brain [ 28 – 31 ]. There is less evidence that dopamine [ 32 – 34 ], oxytocin [ 35 – 37 ], or vasopressin [ 38 , 39 ] could be influenced by placental genes ( S1 Fig ).…”