Changes in myometrial expression of progesterone receptor membrane components 1 and 2 are associated with human parturition at term

Abstract

While the exact mechanism of human parturition remains unknown, functional progesterone withdrawal is believed to play a key regulatory role. Progesterone receptor membrane components 1 and 2 (PGRMC1, PGRMC2) are putative progesterone receptors and the aim of this project was to investigate their expression in human myometrium. Human term myometrium was obtained from the lower uterine segment incision in women undergoing elective (not-in-labour, NIL; n=11) and emergency Caesarean sections (in-labour, IL; n=10), following written consent. PGRMC1 and 2 expression was quantified using real-time reverse transcription polymerase chain reaction and western blot. Subcellular localisation was performed by immunohistochemistry and immunofluorescence. There was a significant decrease in PGRMC1 mRNA (P=0.0317) and protein expression (P=0.0151) in IL myometrium, compared with NIL myometrium. PGRMC2 mRNA expression (P=0.0151) was also decreased in IL myometrium, compared with NIL myometrium. Immunostaining studies confirmed the presence of PGRMC1 and 2 in smooth-muscle cells. Expression was perinuclear in NIL myometrium and more generalised and cytoplasmic in IL myometrium. The decrease in PGRMC1 expression and the translocation away from a perinuclear location for both PGRMC1 and 2 could contribute to a functional progesterone withdrawal that may ultimately initiate parturition.

Roles of Progesterone Receptor Membrane Component 1 in Oxidative Stress—Induced Aging in Chorion Cells

“…30 –33 It is differentially expressed in gestational tissues and may ultimately contribute to fetal membrane rupture and initiation of parturition. 34 –37 Other studies have also demonstrated the protective role of PGRMC1 in oxidative damage in human breast cancer cells 30 and neuronal cultures. 33 More strikingly, it was reported that PGRMC1 might be associated with premature aging of the reproductive tract.…”

What Do We Know about Classical and Non-Classical Progesterone Receptors in the Human Female Reproductive Tract? A Review

“…The P4 non-classical pathways’ faster action is believed to directly affect myometrial contraction by either modulating intracellular signal transduction pathways [ 4 , 54 ] or inhibiting calcium influx [ 169 ]. Several studies about the myometrial contractility of pregnant women have demonstrated the presence of mPRα, mPRβ, PGRMC1, and PGRMC2 in human myometrial cells [ 57 , 94 , 100 , 170 ].…”

“…Changes in these receptors could potentially contribute to functional P4 withdrawal in the human myometrium during labor. PGRMC2 and PGRMC1 expression levels are significantly lower in in-labor women than into non-in-labor women [ 170 ]. In contrast, Wu et al found no significant differences in PGRMC1 mRNA expression, contrarily to protein expression, between term and preterm myometria.…”

Estrogens modulate progesterone receptor expression and may contribute to progesterone-mediated apoptotic β-cell death

“…28 Among these, the progesterone receptor membrane component 1 (PGRMC1) has been identified as an important novel mediator of progesterone function, being demonstrated that PGRMC1 is differentially expressed in fetal membranes among pregnant women and it is diminished in preterm delivery. 29 Wang et al, 30 reported that the decrease in PGRMC1 expression and its translocation from a perinuclear location could contribute to a functional progesterone withdrawal that may ultimately initiate parturition. However, little is known about this receptor role in pancreatic tissue, and specifically in b-cells.…”