Endometrial Decidualization: The Primary Driver of Pregnancy Health
Abstract
:1. Introduction
2. Biological Continuum of Adverse Pregnancy Outcome
3. Implantation and Placentation
4. It’s the Quality of the Soil, Not the Seed
- A critical period of time exists within each menstrual cycle—known as the ‘window of implantation’—in which the endometrium is maximally receptive to the blastocyst. This period is personalized and implantation outside of this 24–36 h window will result in an absolute failure to establish a pregnancy or in suboptimal implantation increasing the risk of a range of downstream adverse pregnancy events [25,26].
- In contrast to the ‘window of implantation’ in the endometrium, embryos generated by IVF can be transferred into the uterus any time between days 2 and 7 postconception [27].
- Embryos can be frozen and thawed multiple times prior to transfer.
- Pregnancy outcomes appear to be better in frozen rather than fresh cycles [30]. A plausible explanation might be that the hormonal manipulations used to prepare the endometrium for existing cryopreserved embryos are more favorable to the endometrium than protocols used in fresh cycles, which are designed primarily to maximize the number of oocytes retrieved.
- Lastly, although the presence of a decidua is not an absolute requirement for implantation since the blastocyst can implant in the fallopian tube, the cervix, or even into the vasculature of the bowel in the case of extrauterine intraabdominal ectopic pregnancies, such pregnancies are rarely healthy and, if they do go past 20 weeks, have a high rate of complications.
5. The Decidua as an Anatomically Distinct Autocrine/Paracrine Organ
6. Endometrial Decidualization
7. Evolution of the Decidua
8. Timing of Decidualization
9. Master Regulators of Decidualization
- Hormonal factors. During the follicular phase of the menstrual cycle, estrogen production by ovarian granulosa cells causes the endometrium to proliferate and thicken. The major driver of decidualization is progesterone, which is produced by the corpus luteum of the ovary following ovulation. In the absence of a conceptus, the corpus luteum is programmed to regress in 14 days, resulting in systemic progesterone withdrawal and menstruation. In the presence of a pregnancy, production of human chorionic gonadotropin (hCG) by trophoblast cells prevents luteolysis, thereby maintaining progesterone production until the placenta takes over this functionality at 5–7 weeks of gestation [56]. Moreover, the local production of hormones such as relaxin and corticotropin-releasing hormone (CRH) in response to the hCG surge establishes an autocrine/paracrine regulatory loop to enhance intracellular cAMP levels in ESCs, promote decidualization, and support implantation and early pregnancy [57,58,59].
- Biochemical factors. There is increasing evidence to suggest that biochemical/metabolic factors are important in decidualization. For example, lipid mediators such as lysophosphatidic acid (LPA) are produced by uterine epithelium [60] and regulate heparin-binding epidermal growth factor (HB-EGF) [61] and epidermal growth factor receptor (EGFR) signaling as well as cyclooxygenase 2 (COX2) [62] and thereby prostaglandin E2 (PGE2) production, which together with interferon-γ control the spatial decidualization of ESCs [63,64]. Other autocrine/ paracrine factors—including interleukins, such as IL-1β, IL-11, and leukemia inhibitory factor (LIF) [65,66,67,68,69] as well as transforming growth factor-beta (TGF-β superfamily members such as activin, TGF-β1, bone morphogenesis protein 2 (BMP2), and left–right determination factor 2 (LEFTY2) [70,71,72,73]—also appear to be important in sustaining the decidualization process, promoting cAMP and extracellular matrix (ECM) signaling, regulating angiogenesis, and supporting embryo implantation. Glucose also serves as a metabolic signal for decidualization, providing a link between glycemic control and cellular oxidative stress (discussed below).
- Immunological factors. The importance of the immunological priming of the endometrium is becoming increasingly apparent. While this is driven, in part, by intrinsic factors, including a range of endocrine and autocrine/paracrine signals [3,17,35], extrinsic factors are likely also involved. One such factor is exposure to seminal fluid both prior to and around the time of implantation [74,75,76]. Interestingly, this exposure does not have to be local. Exposure to paternal antigen via nonvaginal routes can also prime the endometrium immunologically [77]. Although the mechanism responsible for this priming effect is not clear, seminal fluid contains soluble and exosome-borne signaling agents that promote leukocyte recruitment and generation of regulatory T cells (Treg cells) which suppress inflammation, promote vascular adaptation, and foster tolerance towards fetal antigens [78]. This mechanism could shed light on a number of well-recognized risk factors for the ‘great obstetrical syndromes’ that have thus far defied explanation. Why is it that nulliparity, young maternal age, IVF conception, the use of donor sperm, the short length of cohabitation, short inter-pregnancy interval, and the use of barrier contraception are risk factors for conditions such as preeclampsia and PTB? Could the common factor be a lack of exposure to protective seminal fluid? Recent data suggest that intercourse during IVF treatment cycles improves implantation success and pregnancy health [79], which is consistent with the hypothesis that exposure to seminal fluid promotes healthy decidualization and implantation.
10. Molecular Regulation of Decidualization
- Genomic progesterone signaling pathways mediated by the nuclear progesterone receptor (nPGR). nPGR is the dominant member of the 3-ketosteroid nuclear receptor family that responds to progesterone and cyclic AMP/protein kinase A (cAMP/PKA) signaling during decidualization [88,89]. A recent study that employed both RNA-sequencing and PGR chromatin-immunoprecipitation (ChIP)-sequencing of endometrium during the window of implantation showed that the PGR signaling network is made up of multiple different classical signaling pathways and involves numerous downstream regulators [90], including Indian hedgehog (IHH) [91], heart and neural crest derivatives-expressed (HAND2) [92], transcription factors Forkhead Box O1 (FOXO1) [93], SPR-related HMG-box gene 17 (SOX17) [94] and signal transducers and activators of transcription (STAT) transcription factor members (STAT1, STAT3, STAT5) [95], Notch signaling [96], insulin receptor substrate 2 (IRS2) [97], BMP2 and WNT signaling [72], HOXA10 [98], CCAAT/enhancer-binding protein β (CEBPB) [99], EGFR [100], mammalian target of rapamycin complex 1 (MTORC1) [101], and the tumor necrosis factor alpha-nuclear factor kappa-light-chain-enhancer of activated B cells’ (TNFα/NFκβ) pathway [102]. These pathways play an important role in the embryo–uterine, epithelial–stromal, and stromal–immune cell crosstalk that occurs in the peri-implantation period and is responsible for such functions as EMT, insulin resistance, focal adhesion, trophoblast invasion, regulation of the complement and coagulation cascade, cytokine-cytokine receptor interactions, xenobiotics metabolism, inflammatory response, ECM receptor interaction, angiogenesis and vasculature development, apoptosis, cytoskeleton remodeling, and the secretion of glycogen and other decidualization markers, such as PRL and insulin-like binding factor (IGFBP1). In a proteome and secretome screening study of in vitro decidualized ESCs, Garrido-Gomez et al. [103] reported that, in addition to PRL and IGFBP1, a number of other secreted decidualization markers might be involved in the attendant angiogenesis, including platelet/endothelial cell adhesion molecule-1 (PECAM-1) and myeloid progenitor inhibitory factor-1 (MPIF-1). In another study of 23 secreted factors derived from primary ESCs prior to ART, coordinated and synchronized changes in the secretome were associated with successful implantation, whereas cultures from the failed implantation group typically demonstrated a disordered secretome profile [104].
- Non-genomic progesterone functions not mediated by nPGR. Recent studies have revealed the presence of membrane-associated putative progesterone-binding proteins, such as PGR membrane component 1 and 2 (PGRMC1, PGRMC2) [105] and progestin and adiponectin receptors (PAQRs) [106], in cycling endometrium and pregnancy tissues that can rapidly activate downstream signal transduction pathways to mediate non-genomic functions of progesterone, including interacting with PGR [107] and other steroid receptors [108], regulating endometrial receptivity [109], and triggering and promoting parturition [110,111]. The functional importance of these membrane-associated proteins in decidualization remains unknown. However, in addition to nPGR, other members of the 3-keto-steroid nuclear receptor family—such as glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and androgen receptor (AR)—have also been found to play an important role in decidualization. In an in vitro decidualization model in which ESCs were induced with 8-bromo-cAMP (8-Br-cAMP) and medroxyprogesterone acetate (MPA), Cloke et al. demonstrated that AR regulated the expression of a distinct decidual gene network with a preponderance of upregulated genes being involved in cytoskeletal organization and cell motility and repressed genes being involved in cell cycle regulation [112]. Moreover, Kuroda et al. reported that progesterone/cAMP induction of ESCs increased expression of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, which converts inert cortisone to active cortisol and thus contributed to the metabolic regulation in decidualizing ESCs [113]. Taken together, these data suggest that the decidualization of ESCs involves the integration of multiple nonredundant signaling networks in response to progesterone stimulation.
- Metabolic regulators. The increased 11β-HSD1 expression and activity associated with ESC decidualization leads to a decrease in GR and reciprocal increase in MR expression [113]. The upregulation of MR-dependent genes, in turn, affects lipid droplet biogenesis and retinoid metabolism. For example, 11β-HSD1 upregulates dehydrogenase/reductase 3 (DHRS3) expression, which promotes retinol storage in lipid droplets [113]. Retinoic acid (RA) is essential in the maintenance of pregnancy and its metabolism is tightly controlled at the maternal–fetal interface [114]. The decidualization of ESCs increases the expression of retinol-binding protein 4 (RBP4) and cytochrome P450 26A1 (CYP26A1) involved in RA metabolism and downregulates the expression of the pro-apoptotic RA nuclear receptor (RAR) [115]. The lipid mediator LPA also regulates EGFR signaling, COX2 expression, and prostaglandin signaling for the spatial decidualization of ESCs [63,64]. COX2 in turn activates uterine peroxisome proliferator-activated receptor-delta (PPAR-δ) and retinoid X receptor (RXR), which are critical regulators of decidualization and implantation [116]. Omega-3 polyunsaturated fatty acids have been shown in numerous animal and clinical studies to be beneficial for pregnancy outcome [117]. The receptor GPR120, a member of the rhodopsin family of G protein-coupled receptors, mediates potent anti-inflammatory and insulin- sensitizing effects [118]. Huang et al. showed that GPR120 could promote decidualization by upregulating FOXO1 and glucose transporter-1 (GLUT1) expression, glucose uptake, and pentose-phosphate pathway activation in ESCs [119].
- MicroRNA (miRNA) and epigenetic regulation. Using the miRNA profiling of ESC primary cultures before and after in vitro decidualization, Estella et al. reported an upregulation of 26 miRNAs and the downregulation of miR-96, miR-135b, miR-181 and miR-183 [128]. The addition of miR-96 and miR-135b in decidualizing ESCs decreased the expression of FOXO1 and HOXA10 as well as IGFBP-1 secretion [128]. In another study, Jimenez et al. reported that the upregulation of the miR-200 family during in vitro decidualization of ESCs correlated with the downregulation of IHH signaling and expression of the EMT regulator, ZEB1 [129]. Similar studies have demonstrated the functional importance also of miR-181a [130], miR-542-3p [131], and miR-194-3p [132] in decidualization. While individual miRNAs can regulate a range of target genes, there is growing evidence that endometrial cells undergo genome-wide chromatin remodeling for the access of transcription factors or epigenetic modifiers during decidualization [133,134]. In particular, the expression of the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) appears to be reduced in endometrium beginning in the mid-secretory phase of the menstrual cycle and specifically in decidualizing ESCs [135]. The knockdown of Ezh2 in decidualizing human ESCs resulted in reduced levels of trimethylated lysine 27 of histone 3 (H3K27me3), a repressive histone mark for silenced genes, in the proximal promoter regions of the PRL and IGFBP1 genes, with a reciprocal enhancement of histone acetylation and concomitant higher expression of these two gene products [136]. A recent combined H3K27me3 ChIP-Seq and RNA-Seq analysis of mouse decidual cells harvested at different gestation stages confirmed the H3K27me3-induced transcriptional silencing of target genes that specifically suppress inflammation and contractile function in early gestation. In late gestation, genome-wide H3K27me3 demethylation was observed, thereby allowing de-repression and target gene upregulation to lead to the onset of labor [136]. Moreover, the pharmacological inhibition of H23K27 demethylation was able to inhibit labor and delivery while maintaining pup viability in a PTB murine model [136], thereby demonstrating the functional importance of this molecular mechanism. These data are consistent with the hypothesis that parturition in humans is nothing more than a delayed menstruation [11]. Although intriguing, it should be noted that the function of EZH2 and genome-wide chromatin remodeling in the process of human decidualization and implantation remains unclear. Additional studies are needed to further investigate these epigenetic regulatory mechanisms within the various uterine compartments and their association with pregnancy outcome.
11. Decidualization Resistance and Pregnancy Complications
- Preeclampsia is a pregnancy-specific disorder characterized by new-onset hypertension and maternal end-organ damage after 20 weeks’ gestation that complicates 5–7% of all pregnancies. The pathologic hallmark is shallow trophoblast invasion and a failure of spiral artery remodeling. The current model posits that the primary cause of this suboptimal endovascular invasion is a failure of the decidua to tolerate and/or facilitate trophoblast invasion. In support of this hypothesis, Garrido-Gomez et al. identified a transcriptomic fingerprint characterizing a decidualization defect in the endometrium of women with a history of severe preeclampsia that is linked to impaired cytotrophoblast invasion. Moreover, this defect was detected at the time of delivery and persisted for years thereafter [137]. The decidualization of ESCs is mediated, at least in part, by annexin A2 (ANXA2) and the maternal deficiency of the ANXA2 gene contributes to shallow decidual invasion by placental cytotrophoblast cells [138]. These findings highlight the maternal contribution to the pathogenesis of severe preeclampsia.
- Recurrentpregnancy loss, defined as 3 or more consecutive miscarriages, is a condition experienced by 1–2% of all couples. The cause is poorly understood. It is widely attributed to either repeated chromosomal instability in the conceptus or ill-defined uterine factors. Recent studies suggest that such women have impaired cyclic decidualization that predisposes to pregnancy failure by disrupting the maternal response to hormonal signaling leading to the dysregulation of decidualization markers, including, among others, prolactin, prokineticin, and the genes DIO2 and SCARA5 [139,140].
- A similar mechanism may account for the increased risk of adverse pregnancy events in women with poorly controlled pregestational diabetes. In such women, strict glycemic control around the time of conception has been shown to reduce rates of miscarriage and birth defects (diabetic embryology) and to improve overall pregnancy outcome [141].
12. Prevention of Pregnancy Complications
13. Future Direction
14. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
11β-HSD1 | 11β-hydroxysteroid dehydrogenase type 1 |
AR | androgen receptor |
BCAT | branched chain amino acid transferase |
BMP2 | bone morphogenesis protein 2 |
COX2 | cyclooxygenase 2 |
CRABP2 | cellular retinoic acid binding protein 2 |
CRH | corticotropin-releasing hormone |
CXCL1 | C-X-C motif chemokine ligand 2 |
DKK1 | Dickkopf WNT signaling pathway inhibitor 1 |
DSC | decidual stromal cell |
EGF | epidermal growth factor |
EGFR | epidermal growth factor receptor |
EOGT | EGF domain specific O-linked N-acetylglucosamine transferase |
ERK | extracellular- signal-regulated kinase |
ESC | endometrial stromal cell |
FABP5 | fatty acid binding protein 5 |
FOXO1 | transcription factors Forkhead Box O1 |
FZD5 | Frizzled 5 |
GR | glucocorticoid receptor |
HAND2 | heart and neural crest derivatives-expressed 2 |
HB-EGF | heparin binding EGF-like growth factor |
HSP | heat shock protein |
IFN | interferon |
IGFBP1 | insulin-like growth factor binding protein 1 |
IL-1β | interleukin-1β |
IHH | Indian hedgehog |
LEFTY2 | left-right determination factor 2 |
LIF | leukemia inhibitory factor |
LPA | lysophosphatidic acid |
LRP6 | LDL receptor related protein 6 |
MAPK | mitogen activated protein kinase |
MET | mesenchymal-epithelial transition |
miRNA | microRNA |
MPIF-1 | myeloid progenitor inhibitory factor-1 |
mPR | membrane progesterone receptor |
MR | mineralocorticoid receptor |
MTORC1 | mammalian target of rapamycin complex 1 |
NK cells | natural killer cells |
nPR | nuclear progesterone receptor |
PAQRs | progestin and adiponectin receptors |
PCa+ | prostate cancer a protein |
PECAM-1 | platelet-endothelial cell adhesion molecule-1 |
PGE2 | prostaglandin E2 |
PGRMC1 | PGR membrane component 1 |
PPAR-δ | peroxisome proliferator-activated receptor-delta |
PUFA | polyunsaturated fatty acids |
RBP4 | retinol-binding protein 4 |
ROS | reactive oxygen species |
RXR | retinoid X receptor |
SFRP4 | secreted frizzled-related protein 4 |
TGF-β | transforming growth factor-β |
TNFα/NFκβ | tumor necrosis factor alpha-nuclear factor kappa-light-chain-enhancer of activated B cells |
DC | dendritic cells |
dNK | decidual natural killer cells |
DSCs | decidual stromal cells |
EGFR | epidermal growth factor receptor |
ESCs | endometrial stromal cells |
HB-EGF | heparin binding EGF-like growth factor |
EMT | epithelial-mesenchymal transition |
hCG | human chorionic gonado-tropin |
IGFBP1 | isulin-like growth factor binding protein 1 |
IFN | interferon |
IL-1β | interleukin-1β |
ROS | reactive oxygen species |
LIF | leukemia inhibitory factor |
MET | mesenchymal-epithelial transition |
miRNA | microRNA |
MMP | matrix metalloproteinase |
PGS | prostaglandins |
TGF-β | transforming growth factor-β |
TIMP | tissue inhibitor of meatalloproteinase |
VEGF | vascular endothelial growth factor |
References
- Cross, J.C.; Werb, Z.; Fisher, S.J. Implantation and the placenta: Key pieces of the development puzzle. Science 1994, 266, 1508–1518. [Google Scholar] [CrossRef] [PubMed]
- Norwitz, E.R.; Schust, D.J.; Fisher, S.J. Implantation and the survival of early pregnancy. N. Engl. J. Med. 2001, 345, 1400–1408. [Google Scholar] [CrossRef] [PubMed]
- Norwitz, E.R. Defective implantation and placentation: Laying the blueprint for pregnancy complications. Reprod. Biomed. Online 2006, 13, 591–599. [Google Scholar] [CrossRef]
- Brosens, I.; Pijnenborg, R.; Vercruysse, L.; Romero, R. The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am. J. Obstet. Gynecol. 2011, 204, 193–201. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Redman, C.W.; Sargent, I.L. Immunology of pre-eclampsia. Am. J. Reprod. Immunol. 2010, 63, 534–543. [Google Scholar] [CrossRef]
- Cha, J.; Sun, X.; Dey, S.K. Mechanisms of implantation: Strategies for successful pregnancy. Nat. Med. 2012, 18, 1754–1767. [Google Scholar] [CrossRef]
- Redman, C.W.; Tannetta, D.S.; Dragovic, R.A.; Gardiner, C.; Southcombe, J.H.; Collett, G.P.; Sargent, I.L. Review: Does size matter? Placental debris and the pathophysiology of pre-eclampsia. Placenta 2012, 33, S48–S54. [Google Scholar] [CrossRef]
- Brosens, I.; Puttemans, P.; Benagiano, G. Placental bed research: I. The placental bed: From spiral arteries remodeling to the great obstetrical syndromes. Am. J. Obstet. Gynecol. 2019, 221, 437–456. [Google Scholar] [CrossRef]
- Emera, D.; Romero, R.; Wagner, G. The evolution of menstruation: A new model for genetic assimilation: Explaining molecular origins of maternal responses to fetal invasiveness. Bioessays 2012, 34, 26–35. [Google Scholar] [CrossRef] [Green Version]
- Jarrell, J. The significance and evolution of menstruation. Best Pract. Res. Clin. Obstet. Gynaecol. 2018, 50, 18–26. [Google Scholar] [CrossRef]
- Pavlicev, M.; Norwitz, E.R. Human parturition: Nothing more than a delayed menstruation. Reprod. Sci. 2018, 25, 166–173. [Google Scholar] [CrossRef] [PubMed]
- Dugoff, L.; Society for Maternal-Fetal Medicine. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes. Obstet. Gynecol. 2010, 115, 1052–1061. [Google Scholar] [CrossRef] [PubMed]
- Burton, G.J.; Jauniaux, E. Pathophysiology of placental-derived fetal growth restriction. Am. J. Obstet. Gynecol. 2018, 218, S745–S761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wilcox, A.J.; Weinberg, C.R.; O’Connor, J.F.; Baird, D.D.; Schlatterer, J.P.; Canfield, R.E.; Armstrong, E.G.; Nisula, B.C. Incidence of early loss of pregnancy. N. Engl. J. Med. 1988, 319, 189–194. [Google Scholar] [CrossRef] [PubMed]
- Zinaman, M.J.; Clegg, E.D.; Brown, C.C.; O’Connor, J.; Selevan, S.G. Estimates of human fertility and pregnancy loss. Fertil. Steril. 1996, 65, 503–509. [Google Scholar] [CrossRef]
- Simón, C.; Valbuena, D. Embryonic implantation. Ann. Endocrinol. 1999, 60, 134–136. [Google Scholar]
- Harris, L.K.; Benagiano, M.; D’Elios, M.M.; Brosens, I.; Benagiano, G. Placental bed research: II. Functional and immunological investigations of the placental bed. Am. J. Obstet. Gynecol. 2019, 221, 457–469. [Google Scholar] [CrossRef]
- Jauniaux, E.; Poston, L.; Burton, G.J. Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution. Hum. Reprod. Update 2006, 12, 747–755. [Google Scholar] [CrossRef] [Green Version]
- Red-Horse, K.; Zhou, Y.; Genbacev, O.; Prakobphol, A.; Foulk, R.; McMaster, M.; Fisher, S.J. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J. Clin. Investig. 2004, 114, 744–754. [Google Scholar] [CrossRef]
- Gaynor, L.M.; Colucci, F. Uterine natural killer cells: Functional distinctions and influence on pregnancy in humans and mice. Front. Immunol. 2017, 8, 467. [Google Scholar] [CrossRef] [Green Version]
- Pijnenborg, R.; Bland, J.M.; Robertson, W.B.; Brosens, I. Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy. Placenta 1983, 4, 397–413. [Google Scholar] [CrossRef]
- Craven, C.M.; Morgan, T.; Ward, K. Decidual spiral artery remodelling begins before cellular interaction with cytotrophoblasts. Placenta 1998, 19, 241–252. [Google Scholar] [CrossRef]
- Su, R.W.; Fazleabas, A.T. Implantation and establishment of pregnancy in human and nonhuman primates. Adv. Anat. Embryol. Cell Biol. 2015, 216, 189–213. [Google Scholar] [CrossRef] [Green Version]
- Blue, N.R.; Page, J.M.; Silver, R.M. Genetic abnormalities and pregnancy loss. Semin. Perinatol. 2019, 43, 66–73. [Google Scholar] [CrossRef] [PubMed]
- Valdes, C.T.; Schutt, A.; Simon, C. Implantation failure of endometrial origin: It is not pathology, but our failure to synchronize the developing embryo with a receptive endometrium. Fertil. Steril. 2017, 108, 15–18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Franasiak, J.M.; Ruiz-Alonso, M.; Scott, R.T.; Simón, C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil. Steril. 2016, 105, 861–866. [Google Scholar] [CrossRef] [Green Version]
- Glujovsky, D.; Farquhar, C.; Quinteiro Retamar, A.M.; Alvarez Sedo, C.R.; Blake, D. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst. Rev. 2016, 6, CD002118. [Google Scholar] [CrossRef]
- Van der Hoorn, M.L.; Lashley, E.E.; Bianchi, D.W.; Claas, F.H.; Schonkeren, C.M.; Scherjon, S.A. Clinical and immunologic aspects of egg donation pregnancies: A systematic review. Hum. Reprod. Update 2010, 16, 704–712. [Google Scholar] [CrossRef]
- Van Bentem, K.; Bos, M.; van der Keur, C.; Brand-Schaaf, S.H.; Haasnoot, G.W.; Roelen, D.L.; Eikmans, M.; Heidt, S.; Claas, F.H.J.; Lashley, E.E.L.O.; et al. The development of preeclampsia in oocyte donation pregnancies is related to the number of fetal-maternal HLA class II mismatches. J. Reprod. Immunol. 2020, 137, 103074. [Google Scholar] [CrossRef]
- Wei, D.; Liu, J.Y.; Sun, Y.; Shi, Y.; Zhang, B.; Liu, J.Q.; Tan, J.; Liang, X.; Cao, Y.; Wang, Z.; et al. Frozen versus fresh single blastocyst transfer in ovulatory women: A multicentre, randomised controlled trial. Lancet 2019, 393, 1310–1318. [Google Scholar] [CrossRef]
- Bulmer, J.N.; Morrison, L.; Longfellow, M.; Ritson, A.; Pace, D. Granulated lymphocytes in human endometrium: Histochemical and immunohistochemical studies. Hum. Reprod. 1991, 6, 791–798. [Google Scholar] [CrossRef] [PubMed]
- Starkey, P.M.; Sargent, I.L.; Redman, C.W. Cell populations in human early pregnancy decidua: Characterization and isolation of large granular lymphocytes by flow cytometry. Immunology 1988, 65, 129–134. [Google Scholar]
- Vince, G.S.; Starkey, P.M.; Jackson, M.C.; Sargent, I.L.; Redman, C.W. Flow cytometric characterisation of cell populations in human pregnancy decidua and isolation of decidual macrophages. J. Immunol. Methods 1990, 132, 181–189. [Google Scholar] [CrossRef]
- Du, H.; Taylor, H.S. Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem. Cells 2007, 25, 2082–2086. [Google Scholar] [CrossRef] [PubMed]
- Evans, J.; Salamonsen, L.A.; Winship, A.; Menkhorst, E.; Nie, G.; Gargett, C.E.; Dimitriadis, E. Fertile ground: Human endometrial programming and lessons in health and disease. Nat. Rev. Endocrinol. 2016, 12, 654–667. [Google Scholar] [CrossRef]
- Fox, C.; Morin, S.; Jeong, J.W.; Scott, R.T., Jr.; Lessey, B.A. Local and systemic factors and implantation: What is the evidence? Fertil. Steril. 2016, 105, 873–884. [Google Scholar] [CrossRef] [Green Version]
- Yang, F.; Zheng, Q.; Jin, L. Dynamic function and composition changes of immune cells during normal and pathological pregnancy at the maternal-fetal interface. Front. Immunol. 2019, 10, 2317. [Google Scholar] [CrossRef] [Green Version]
- Houser, B.L.; Tilburgs, T.; Hill, J.; Nicotra, M.L.; Strominger, J.L. Two unique human decidual macrophage populations. J. Immunol. 2011, 186, 2633–2642. [Google Scholar] [CrossRef] [Green Version]
- Lash, G.E.; Pitman, H.; Morgan, H.L.; Innes, B.A.; Agwu, C.N.; Bulmer, J.N. Decidual macrophages: Key regulators of vascular remodeling in human pregnancy. J. Leukoc. Biol. 2016, 100, 315–325. [Google Scholar] [CrossRef] [Green Version]
- Van der Zwan, A.; Bi, K.; Norwitz, E.R.; Crespo, A.C.; Claas, F.H.J.; Strominger, J.L.; Tilburgs, T. Mixed signature of activation and dysfunction allows human decidual CD8(+) T cells to provide both tolerance and immunity. Proc. Natl. Acad. Sci. USA 2018, 115, 385–390. [Google Scholar] [CrossRef] [Green Version]
- Crespo, A.C.; Strominger, J.L.; Tilburgs, T. Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection. Proc. Natl. Acad. Sci. USA 2016, 113, 15072–15077. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Erlebacher, A. Immunology of the maternal-fetal interface. Ann. Rev. Immunol. 2013, 31, 387–411. [Google Scholar] [CrossRef] [PubMed]
- Kin, K.; Maziarz, J.; Chavan, A.R.; Kamat, M.; Vasudevan, S.; Birt, A.; Emera, D.; Lynch, V.J.; Ott, T.L.; Pavlicev, M.; et al. The transcriptomic evolution of mammalian pregnancy: Gene expression innovations in endometrial stromal fibroblasts. Genome Biol. Evol. 2016, 8, 2459–2473. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chavan, A.R.; Bhullar, B.A.; Wagner, G.P. What was the ancestral function of decidual stromal cells? A model for the evolution of eutherian pregnancy. Placenta 2016, 40, 40–51. [Google Scholar] [CrossRef] [Green Version]
- Carter, A.M. Evolution of placental function in mammals: The molecular basis of gas and nutrient transfer, hormone secretion, and immune responses. Physiol. Rev. 2012, 92, 1543–1576. [Google Scholar] [CrossRef]
- Samuel, C.A. The development of pig trophoblast in ectopic sites. J. Reprod. Fertil. 1971, 27, 494–495. [Google Scholar] [CrossRef]
- Gellersen, B.; Reimann, K.; Samalecos, A.; Aupers, S.; Bamberger, A.M. Invasiveness of human endometrial stromal cells is promoted by decidualization and by trophoblast-derived signals. Hum. Reprod. 2010, 25, 862–873. [Google Scholar] [CrossRef] [Green Version]
- Teklenburg, G.; Salker, M.; Molokhia, M.; Lavery, S.; Trew, G.; Aojanepong, T.; Mardon, H.J.; Lokugamage, A.U.; Rai, R.; Landles, C.; et al. Natural selection of human embryos: Decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. PLoS ONE 2010, 5, e10258. [Google Scholar] [CrossRef]
- Hirota, Y.; Daikoku, T.; Tranguch, S.; Xie, H.; Bradshaw, H.B.; Dey, S.K. Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice. J. Clin. Investig. 2010, 120, 803–815. [Google Scholar] [CrossRef] [Green Version]
- Cha, J.; Hirota, Y.; Dey, S.K. Sensing senescence in preterm birth. Cell Cycle 2012, 11, 205–206. [Google Scholar] [CrossRef] [Green Version]
- Lockwood, C.J.; Krikun, G.; Schatz, F. The decidua regulates hemostasis in human endometrium. Semin. Reprod. Endocrinol. 1999, 17, 45–51. [Google Scholar] [CrossRef] [PubMed]
- Schatz, F.; Guzeloglu-Kayisli, O.; Arlier, S.; Kayisli, U.A.; Lockwood, C.J. The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. Hum. Reprod. Update 2016, 22, 497–515. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Das, S.K.; Lim, H.; Paria, B.C.; Dey, S.K. Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy. J. Mol. Endocrinol. 1999, 22, 91–101. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rasweiler, J.J. Spontaneous decidual reactions and menstruation in the black mastiff bat, Molossus ater. Am. J. Anat. 1991, 191, 1–22. [Google Scholar] [CrossRef] [PubMed]
- Bellofiore, N.; Ellery, S.J.; Mamrot, J.; Walker, D.W.; Temple-Smith, P.; Dickinson, H. First evidence of a menstruating rodent: The spiny mouse (Acomys cahirinus). Am. J. Obstet. Gynecol. 2017, 216, 40.e1–40.e11. [Google Scholar] [CrossRef] [PubMed]
- Carp, H.J.A. Progestogens in luteal support. Horm. Mol. Biol. Clin. Investig. 2020. [Google Scholar] [CrossRef]
- Palejwala, S.; Tseng, L.; Wojtczuk, A.; Weiss, G.; Goldsmith, L.T. Relaxin gene and protein expression and its regulation of procollagenase and vascular endothelial growth factor in human endometrial cells. Biol. Reprod. 2002, 66, 1743–1748. [Google Scholar] [CrossRef] [Green Version]
- Gravanis, A.; Stournaras, C.; Margioris, A.N. Paracrinology of endometrial neuropeptides: Corticotropin-releasing hormone and opioids. Semin. Reprod. Endocrinol. 1999, 17, 29–38. [Google Scholar] [CrossRef]
- Einspanier, A.; Lieder, K.; Husen, B.; Ebert, K.; Lier, S.; Einspanier, R.; Unemori, E.; Kemper, M. Relaxin supports implantation and early pregnancy in the marmoset monkey. Ann. N. Y. Acad. Sci. 2009, 1160, 140–146. [Google Scholar] [CrossRef]
- Aikawa, S.; Kano, K.; Inoue, A.; Wang, J.; Saigusa, D.; Nagamatsu, T.; Hirota, Y.; Fujii, T.; Tsuchiya, S.; Taketomi, Y.; et al. Autotaxin-lysophosphatidic acid-LPA3 signaling at the embryo-epithelial boundary controls decidualization pathways. EMBO J. 2017, 36, 2146–2160. [Google Scholar] [CrossRef]
- Chobotova, K.; Karpovich, N.; Carver, J.; Manek, S.; Gullick, W.J.; Barlow, D.H.; Mardon, H.J. Heparin-binding epidermal growth factor and its receptors mediate decidualization and potentiate survival of human endometrial stromal cells. J. Clin. Endocrinol. Metab. 2005, 90, 913–919. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lim, H.; Paria, B.C.; Das, S.K.; Dinchuk, J.E.; Langenbach, R.; Trzaskos, J.M.; Dey, S.K. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 1997, 91, 197–208. [Google Scholar] [CrossRef] [Green Version]
- Milne, S.A.; Perchick, G.B.; Boddy, S.C.; Jabbour, H.N. Expression, localization, and signaling of PGE(2) and EP2/EP4 receptors in human nonpregnant endometrium across the menstrual cycle. J. Clin. Endocrinol. Metab. 2001, 86, 4453–4459. [Google Scholar] [CrossRef] [PubMed]
- Christian, M.; Marangos, P.; Mak, I.; McVey, J.; Barker, F.; White, J.; Brosens, J.J. Interferon-gamma modulates prolactin and tissue factor expression in differentiating human endometrial stromal cells. Endocrinology 2001, 142, 3142–3151. [Google Scholar] [CrossRef]
- Dimitriadis, E.; Salamonsen, L.A.; Robb, L. Expression of interleukin-11 during the human menstrual cycle: Coincidence with stromal cell decidualization and relationship to leukaemia inhibitory factor and prolactin. Mol. Hum. Reprod. 2000, 6, 907–914. [Google Scholar] [CrossRef] [Green Version]
- Tamura, M.; Sebastian, S.; Yang, S.; Gurates, B.; Fang, Z.; Bulun, S.E. Interleukin-1beta elevates cyclooxygenase-2 protein level and enzyme activity via increasing its mRNA stability in human endometrial stromal cells: An effect mediated by extracellularly regulated kinases 1 and 2. J. Clin. Endocrinol. Metab. 2002, 87, 3263–3273. [Google Scholar] [CrossRef] [Green Version]
- Dey, S.K.; Lim, H.; Das, S.K.; Reese, J.; Paria, B.C.; Daikoku, T.; Wang, H. Molecular cues to implantation. Endocr. Rev. 2004, 25, 341–373. [Google Scholar] [CrossRef]
- Cullinan, E.B.; Abbondanzo, S.J.; Anderson, P.S.; Pollard, J.W.; Lessey, B.A.; Stewart, C.L. Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. Proc. Natl. Acad. Sci. USA 1996, 93, 3115–3120. [Google Scholar] [CrossRef] [Green Version]
- Shuya, L.L.; Menkhorst, E.M.; Yap, J.; Li, P.; Lane, N.; Dimitriadis, E. Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice. PLoS ONE 2011, 6, e25288. [Google Scholar] [CrossRef] [Green Version]
- Jones, R.L.; Findlay, J.K.; Farnworth, P.G.; Robertson, D.M.; Wallace, E.; Salamonsen, L.A. Activin A and inhibin A differentially regulate human uterine matrix metalloproteinases: Potential interactions during decidualization and trophoblast invasion. Endocrinology 2006, 147, 724–732. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.R.; Park, D.W.; Lee, J.H.; Choi, D.S.; Hwang, K.J.; Ryu, H.S.; Min, C.K. Progesterone-dependent release of transforming growth factor-beta1 from epithelial cells enhances the endometrial decidualization by turning on the Smad signalling in stromal cells. Mol. Hum. Reprod. 2005, 11, 801–808. [Google Scholar] [CrossRef] [Green Version]
- Li, Q.; Kannan, A.; Wang, W.; Demayo, F.J.; Taylor, R.N.; Bagchi, M.K.; Bagchi, I.C. Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. J. Biol. Chem. 2007, 282, 31725–31732. [Google Scholar] [CrossRef] [Green Version]
- Tang, M.; Naidu, D.; Hearing, P.; Handwerger, S.; Tabibzadeh, S. LEFTY, a member of the transforming growth factor-beta superfamily, inhibits uterine stromal cell differentiation: A novel autocrine role. Endocrinology 2010, 151, 1320–1330. [Google Scholar] [CrossRef] [Green Version]
- Robertson, S.A.; Bromfield, J.J.; Tremellen, K.P. Seminal ’priming’ for protection from pre-eclampsia-a unifying hypothesis. J. Reprod. Immunol. 2003, 59, 253–265. [Google Scholar] [CrossRef]
- Lane, M.; Robker, R.L.; Robertson, S.A. Parenting from before conception. Science 2014, 345, 756–760. [Google Scholar] [CrossRef]
- Saftlas, A.F.; Rubenstein, L.; Prater, K.; Harland, K.K.; Field, E.; Triche, E.W. Cumulative exposure to paternal seminal fluid prior to conception and subsequent risk of preeclampsia. J. Reprod. Immunol. 2014, 101-102, 104–110. [Google Scholar] [CrossRef]
- Koelman, C.A.; Coumans, A.B.; Nijman, H.W.; Doxiadis, I.I.; Dekker, G.A.; Claas, F.H. Correlation between oral sex and a low incidence of preeclampsia: A role for soluble HLA in seminal fluid? J. Reprod. Immunol. 2000, 46, 155–166. [Google Scholar] [CrossRef]
- Guerin, L.R.; Moldenhauer, L.M.; Prins, J.R.; Bromfield, J.J.; Hayball, J.D.; Robertson, S.A. Seminal fluid regulates accumulation of FOXP3+ regulatory T cells in the preimplantation mouse uterus through expanding the FOXP3+ cell pool and CCL19-mediated recruitment. Biol. Reprod. 2011, 85, 397–408. [Google Scholar] [CrossRef] [Green Version]
- Robertson, S.A.; Sharkey, D.J. Seminal fluid and fertility in women. Fertil. Steril. 2016, 106, 511–519. [Google Scholar] [CrossRef] [Green Version]
- Nimbkar-Joshi, S.; Rosario, G.; Katkam, R.R.; Manjramkar, D.D.; Metkari, S.M.; Puri, C.P.; Sachdeva, G. Embryo-induced alterations in the molecular phenotype of primate endometrium. J. Reprod. Immunol. 2009, 83, 65–71. [Google Scholar] [CrossRef]
- Fouladi-Nashta, A.A.; Jones, C.J.; Nijjar, N.; Mohamet, L.; Smith, A.; Chambers, I.; Kimber, S.J. Characterization of the uterine phenotype during the peri-implantation period for LIF-null, MF1 strain mice. Dev. Biol. 2005, 281, 1–21. [Google Scholar] [CrossRef]
- Gardner, D.K. Lactate production by the mammalian blastocyst: Manipulating the microenvironment for uterine implantation and invasion? Bioessays 2015, 37, 364–371. [Google Scholar] [CrossRef] [Green Version]
- Thouas, G.A.; Dominguez, F.; Green, M.P.; Vilella, F.; Simon, C.; Gardner, D.K. Soluble ligands and their receptors in human embryo development and implantation. Endocr. Rev. 2015, 36, 92–130. [Google Scholar] [CrossRef] [Green Version]
- Zhang, X.H.; Liang, X.; Liang, X.H.; Wang, T.S.; Qi, Q.R.; Deng, W.B.; Sha, A.G.; Yang, Z.M. The mesenchymal- epithelial transformation during in vitro decidualization. Reprod. Sci. 2013, 20, 354–360. [Google Scholar] [CrossRef] [Green Version]
- Owusu-Akyaw, A.; Krishnamoorthy, K.; Goldsmith, L.T.; Morelli, S.S. The role of mesenchymal-epithelial transition in endometrial function. Hum. Reprod. Update 2019, 25, 114–133. [Google Scholar] [CrossRef]
- Liu, J.-L.; Wang, T.-S. Systematic analysis of the molecular mechanism underlying decidualization using a text mining approach. PLoS ONE 2015, 10, e0134585. [Google Scholar] [CrossRef]
- Popovici, R.M.; Betzler, N.K.; Krause, M.S.; Luo, M.; Jauckus, J.; Germeyer, A.; Bloethner, S.; Schlotterer, A.; Kumar, R.; Strowitzki, T.; et al. Gene expression profiling of human endometrial-trophoblast interaction in a coculture model. Endocrinology 2006, 147, 5662–5675. [Google Scholar] [CrossRef] [Green Version]
- Gellersen, B.; Brosens, J.J. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr. Rev. 2014, 35, 851–905. [Google Scholar] [CrossRef]
- Wu, S.P.; Li, R.; DeMayo, F.J. Progesterone receptor regulation of uterine adaptation for pregnancy. Trends Endocrinol. Metab. 2018, 29, 481–491. [Google Scholar] [CrossRef]
- Chi, R.A.; Wang, T.; Adams, N.; Wu, S.P.; Young, S.L.; Spencer, T.E.; DeMayo, F. Human endometrial transcriptome and progesterone receptor cistrome reveal important pathways and epithelial regulators. J. Clin. Endocrinol. Metab. 2020, 105. [Google Scholar] [CrossRef]
- Matsumoto, H.; Zhao, X.; Das, S.K.; Hogan, B.L.; Dey, S.K. Indian hedgehog as a progesterone-responsive factor mediating epithelial-mesenchymal interactions in the mouse uterus. Dev. Biol. 2002, 245, 280–290. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Kannan, A.; DeMayo, F.J.; Lydon, J.P.; Cooke, P.S.; Yamagishi, H.; Srivastava, D.; Bagchi, M.K.; Bagchi, I.C. The antiproliferative action of progesterone in uterine epithelium is mediated by Hand2. Science 2011, 331, 912–916. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vasquez, Y.M.; Wang, X.; Wetendorf, M.; Franco, H.L.; Mo, Q.; Wang, T.; Lanz, R.B.; Young, S.L.; Lessey, B.A.; Spencer, T.E.; et al. FOXO1 regulates uterine epithelial integrity and progesterone receptor expression critical for embryo implantation. PLoS Genet. 2018, 14, e1007787. [Google Scholar] [CrossRef]
- Wang, X.; Li, X.; Wang, T.; Wu, S.P.; Jeong, J.W.; Kim, T.H.; Young, S.L.; Lessey, B.A.; Lanz, R.B.; Lydon, J.P.; et al. SOX17 regulates uterine epithelial-stromal cross-talk acting via a distal enhancer upstream of Ihh. Nat. Commun. 2018, 9, 4421. [Google Scholar] [CrossRef]
- Dimitriadis, E.; Stoikos, C.; Tan, Y.L.; Salamonsen, L.A. Interleukin 11 signaling components signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) regulate human endometrial stromal cell differentiation. Endocrinology 2006, 147, 3809–3817. [Google Scholar] [CrossRef]
- Afshar, Y.; Miele, L.; Fazleabas, A.T. Notch1 is regulated by chorionic gonadotropin and progesterone in endometrial stromal cells and modulates decidualization in primates. Endocrinology 2012, 153, 2884–2896. [Google Scholar] [CrossRef] [Green Version]
- Vassen, L.; Wegrzyn, W.; Klein-Hitpass, L. Human insulin receptor substrate-2 (IRS-2) is a primary progesterone response gene. Mol. Endocrinol. 1999, 13, 485–494. [Google Scholar] [CrossRef] [Green Version]
- Lim, H.; Ma, L.; Ma, W.G.; Maas, R.L.; Dey, S.K. Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse. Mol. Endocrinol. 1999, 13, 1005–1017. [Google Scholar] [CrossRef]
- Kannan, A.; Fazleabas, A.T.; Bagchi, I.C.; Bagchi, M.K. The transcription factor C/EBPbeta is a marker of uterine receptivity and expressed at the implantation site in the primate. Reprod. Sci. 2010, 17, 434–443. [Google Scholar] [CrossRef] [Green Version]
- Large, M.J.; Wetendorf, M.; Lanz, R.B.; Hartig, S.M.; Creighton, C.J.; Mancini, M.A.; Kovanci, E.; Lee, K.F.; Threadgill, D.W.; Lydon, J.P.; et al. The epidermal growth factor receptor critically regulates endometrial function during early pregnancy. PLoS Genet. 2014, 10, e1004451. [Google Scholar] [CrossRef] [Green Version]
- Baek, M.O.; Song, H.I.; Han, J.S.; Yoon, M.S. Differential regulation of mTORC1 and mTORC2 is critical for 8-Br-cAMP-induced decidualization. Exp. Mol. Med. 2018, 50, 1–11. [Google Scholar] [CrossRef]
- Sugino, N.; Karube-Harada, A.; Taketani, T.; Sakata, A.; Nakamura, Y. Withdrawal of ovarian steroids stimulates prostaglandin F2alpha production through nuclear factor-kappaB activation via oxygen radicals in human endometrial stromal cells: Potential relevance to menstruation. J. Reprod. Dev. 2004, 50, 215–225. [Google Scholar] [CrossRef] [Green Version]
- Garrido-Gomez, T.; Dominguez, F.; Lopez, J.A.; Camafeita, E.; Quinonero, A.; Martinez-Conejero, J.A.; Pellicer, A.; Conesa, A.; Simon, C. Modeling human endometrial decidualization from the interaction between proteome and secretome. J. Clin. Endocrinol. Metab. 2011, 96, 706–716. [Google Scholar] [CrossRef]
- Peter Durairaj, R.R.; Aberkane, A.; Polanski, L.; Maruyama, Y.; Baumgarten, M.; Lucas, E.S.; Quenby, S.; Chan, J.K.Y.; Raine-Fenning, N.; Brosens, J.J.; et al. Deregulation of the endometrial stromal cell secretome precedes embryo implantation failure. Mol. Hum. Reprod. 2017, 23, 478–487. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pru, J.K.; Clark, N.C. PGRMC1 and PGRMC2 in uterine physiology and disease. Front. Neurosci. 2013, 7, 168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernandes, M.S.; Pierron, V.; Michalovich, D.; Astle, S.; Thornton, S.; Peltoketo, H.; Lam, E.W.; Gellersen, B.; Huhtaniemi, I.; Allen, J.; et al. Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues. J. Endocrinol. 2005, 187, 89–101. [Google Scholar] [CrossRef] [Green Version]
- Karteris, E.; Zervou, S.; Pang, Y.; Dong, J.; Hillhouse, E.W.; Randeva, H.S.; Thomas, P. Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: Potential role in functional progesterone withdrawal at term. Mol. Endocrinol. 2006, 20, 1519–1534. [Google Scholar] [CrossRef] [Green Version]
- Thomas, P.; Pang, Y.; Dong, J. Enhancement of cell surface expression and receptor functions of membrane progestin receptor alpha (mPRalpha) by progesterone receptor membrane component 1 (PGRMC1): Evidence for a role of PGRMC1 as an adaptor protein for steroid receptors. Endocrinology 2014, 155, 1107–1119. [Google Scholar] [CrossRef]
- Garrido-Gomez, T.; Quinonero, A.; Antunez, O.; Diaz-Gimeno, P.; Bellver, J.; Simon, C.; Dominguez, F. Deciphering the proteomic signature of human endometrial receptivity. Hum. Reprod. 2014, 29, 1957–1967. [Google Scholar] [CrossRef] [Green Version]
- Wu, W.; Shi, S.Q.; Huang, H.J.; Balducci, J.; Garfield, R.E. Changes in PGRMC1, a potential progesterone receptor, in human myometrium during pregnancy and labour at term and preterm. Mol. Hum. Reprod. 2011, 17, 233–242. [Google Scholar] [CrossRef] [Green Version]
- Mesiano, S.; Wang, Y.; Norwitz, E.R. Progesterone receptors in the human pregnancy uterus: Do they hold the key to birth timing? Reprod. Sci. 2011, 18, 6–19. [Google Scholar] [CrossRef]
- Cloke, B.; Huhtinen, K.; Fusi, L.; Kajihara, T.; Yliheikkila, M.; Ho, K.K.; Teklenburg, G.; Lavery, S.; Jones, M.C.; Trew, G.; et al. The androgen and progesterone receptors regulate distinct gene networks and cellular functions in decidualizing endometrium. Endocrinology 2008, 149, 4462–4474. [Google Scholar] [CrossRef]
- Kuroda, K.; Venkatakrishnan, R.; Salker, M.S.; Lucas, E.S.; Shaheen, F.; Kuroda, M.; Blanks, A.; Christian, M.; Quenby, S.; Brosens, J.J. Induction of 11beta-HSD 1 and activation of distinct mineralocorticoid receptor- and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells. Mol. Endocrinol. 2013, 27, 192–202. [Google Scholar] [CrossRef] [Green Version]
- Han, B.C.; Xia, H.F.; Sun, J.; Yang, Y.; Peng, J.P. Retinoic acid-metabolizing enzyme cytochrome P450 26a1 (cyp26a1) is essential for implantation: Functional study of its role in early pregnancy. J. Cell. Physiol. 2010, 223, 471–479. [Google Scholar] [CrossRef]
- Ozaki, R.; Kuroda, K.; Ikemoto, Y.; Ochiai, A.; Matsumoto, A.; Kumakiri, J.; Kitade, M.; Itakura, A.; Muter, J.; Brosens, J.J.; et al. Reprogramming of the retinoic acid pathway in decidualizing human endometrial stromal cells. PLoS ONE 2017, 12, e0173035. [Google Scholar] [CrossRef]
- Lim, H.; Gupta, R.A.; Ma, W.G.; Paria, B.C.; Moller, D.E.; Morrow, J.D.; DuBois, R.N.; Trzaskos, J.M.; Dey, S.K. Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev. 1999, 13, 1561–1574. [Google Scholar] [CrossRef]
- Lager, S.; Ramirez, V.I.; Acosta, O.; Meireles, C.; Miller, E.; Gaccioli, F.; Rosario, F.J.; Gelfond, J.A.L.; Hakala, K.; Weintraub, S.T.; et al. Docosahexaenoic acid supplementation in pregnancy modulates placental cellular signaling and nutrient transport capacity in obese women. J. Clin. Endocrinol. Metab. 2017, 102, 4557–4567. [Google Scholar] [CrossRef] [Green Version]
- Oh, D.Y.; Talukdar, S.; Bae, E.J.; Imamura, T.; Morinaga, H.; Fan, W.; Li, P.; Lu, W.J.; Watkins, S.M.; Olefsky, J.M. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010, 142, 687–698. [Google Scholar] [CrossRef] [Green Version]
- Huang, J.; Xue, M.; Zhang, J.; Yu, H.; Gu, Y.; Du, M.; Ye, W.; Wan, B.; Jin, M.; Zhang, Y. Protective role of GPR120 in the maintenance of pregnancy by promoting decidualization via regulation of glucose metabolism. EBioMedicine 2019, 39, 540–551. [Google Scholar] [CrossRef] [Green Version]
- Leitao, B.; Jones, M.C.; Fusi, L.; Higham, J.; Lee, Y.; Takano, M.; Goto, T.; Christian, M.; Lam, E.W.F.; Brosens, J.J. Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals. FASEB J. 2010, 24, 1541–1551. [Google Scholar] [CrossRef] [Green Version]
- Muter, J.; Brighton, P.J.; Lucas, E.S.; Lacey, L.; Shmygol, A.; Quenby, S.; Blanks, A.M.; Brosens, J.J. Progesterone-dependent induction of phospholipase c-related catalytically inactive protein 1 (prip-1) in decidualizing human endometrial stromal cells. Endocrinology 2016, 157, 2883–2893. [Google Scholar] [CrossRef]
- Shah, K.M.; Webber, J.; Carzaniga, R.; Taylor, D.M.; Fusi, L.; Clayton, A.; Brosens, J.J.; Hartshorne, G.; Christian, M. Induction of microRNA resistance and secretion in differentiating human endometrial stromal cells. J. Mol. Cell Biol. 2013, 5, 67–70. [Google Scholar] [CrossRef] [Green Version]
- Kajihara, T.; Jones, M.; Fusi, L.; Takano, M.; Feroze-Zaidi, F.; Pirianov, G.; Mehmet, H.; Ishihara, O.; Higham, J.M.; Lam, E.W.F.; et al. Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization. Mol. Endocrinol. 2006, 20, 2444–2455. [Google Scholar] [CrossRef] [Green Version]
- Muter, J.; Alam, M.T.; Vrljicak, P.; Barros, F.S.V.; Ruane, P.T.; Ewington, L.J.; Aplin, J.D.; Westwood, M.; Brosens, J.J. The glycosyltransferase EOGT regulates adropin expression in decidualizing human endometrium. Endocrinology 2018, 159, 994–1004. [Google Scholar] [CrossRef] [Green Version]
- Burnum, K.E.; Hirota, Y.; Baker, E.S.; Yoshie, M.; Ibrahim, Y.M.; Monroe, M.E.; Anderson, G.A.; Smith, R.D.; Daikoku, T.; Dey, S.K. Uterine deletion of Trp53 compromises antioxidant responses in the mouse decidua. Endocrinology 2012, 153, 4568–4579. [Google Scholar] [CrossRef] [Green Version]
- Lanekoff, I.; Cha, J.; Kyle, J.E.; Dey, S.K.; Laskin, J.; Burnum-Johnson, K.E. Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site. Sci. Rep. 2016, 6, 33023. [Google Scholar] [CrossRef] [Green Version]
- Hirota, Y.; Cha, J.; Yoshie, M.; Daikoku, T.; Dey, S.K. Heightened uterine mammalian target of rapamycin complex 1 (mTORC1) signaling provokes preterm birth in mice. Proc. Natl. Acad. Sci. USA 2011, 108, 18073–18078. [Google Scholar] [CrossRef] [Green Version]
- Estella, C.; Herrer, I.; Moreno-Moya, J.M.; Quinonero, A.; Martinez, S.; Pellicer, A.; Simon, C. miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro. PLoS ONE 2012, 7, e41080. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jimenez, P.T.; Mainigi, M.A.; Word, R.A.; Kraus, W.L.; Mendelson, C.R. miR-200 regulates endometrial development during early pregnancy. Mol. Endocrinol. 2016, 30, 977–987. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Q.; Zhang, H.; Jiang, Y.; Xue, B.; Diao, Z.; Ding, L.; Zhen, X.; Sun, H.; Yan, G.; Hu, Y. MicroRNA-181a is involved in the regulation of human endometrial stromal cell decidualization by inhibiting Kruppel-like factor 12. Reprod. Biol. Endocrinol. 2015, 13, 23. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tochigi, H.; Kajihara, T.; Mizuno, Y.; Mizuno, Y.; Tamaru, S.; Kamei, Y.; Okazaki, Y.; Brosens, J.J.; Ishihara, O. Loss of miR-542-3p enhances IGFBP-1 expression in decidualizing human endometrial stromal cells. Sci. Rep. 2017, 7, 40001. [Google Scholar] [CrossRef]
- Pei, T.; Liu, C.; Liu, T.; Xiao, L.; Luo, B.; Tan, J.; Li, X.; Zhou, G.; Duan, C.; Huang, W. miR-194-3p represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis. Endocrinology 2018, 159, 2554–2562. [Google Scholar] [CrossRef]
- Munro, S.K.; Farquhar, C.M.; Mitchell, M.D.; Ponnampalam, A.P. Epigenetic regulation of endometrium during the menstrual cycle. Mol. Hum. Reprod. 2010, 16, 297–310. [Google Scholar] [CrossRef] [Green Version]
- Grimaldi, G.; Christian, M.; Quenby, S.; Brosens, J.J. Expression of epigenetic effectors in decidualizing human endometrial stromal cells. Mol. Hum. Reprod. 2012, 18, 451–458. [Google Scholar] [CrossRef] [Green Version]
- Grimaldi, G.; Christian, M.; Steel, J.H.; Henriet, P.; Poutanen, M.; Brosens, J.J. Down-regulation of the histone methyltransferase EZH2 contributes to the epigenetic programming of decidualizing human endometrial stromal cells. Mol. Endocrinol. 2011, 25, 1892–1903. [Google Scholar] [CrossRef] [Green Version]
- Nancy, P.; Siewiera, J.; Rizzuto, G.; Tagliani, E.; Osokine, I.; Manandhar, P.; Dolgalev, I.; Clementi, C.; Tsirigos, A.; Erlebacher, A. H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition. J. Clin. Investig. 2018, 128, 233–247. [Google Scholar] [CrossRef] [Green Version]
- Garrido-Gomez, T.; Dominguez, F.; Quiñonero, A.; Diaz-Gimeno, P.; Kapidzic, M.; Gormley, M.; Ona, K.; Padilla-Iserte, P.; McMaster, M.; Genbacev, O.; et al. Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology. Proc. Natl. Acad. Sci. USA 2017, 114, E8468–E8477. [Google Scholar] [CrossRef] [Green Version]
- Garrido-Gomez, T.; Quiñonero, A.; Dominguez, F.; Rubert, L.; Perales, A.; Hajjar, K.A.; Simon, C. Preeclampsia: A defect in decidualization is associated with deficiency of Annexin A2. Am. J. Obstet. Gynecol. 2020, 222, e1–e376. [Google Scholar] [CrossRef]
- Salker, M.; Teklenburg, G.; Molokhia, M.; Lavery, S.; Trew, G.; Aojanepong, T.; Mardon, H.J.; Lokugamage, A.U.; Rai, R.; Landles, C.; et al. Natural selection of human embryos: Impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss. PLoS ONE 2010, 5, e10287. [Google Scholar] [CrossRef] [Green Version]
- Lucas, E.S.; Vrljicak, P.; Muter, J.; Diniz-da-Costa, M.M.; Brighton, P.J.; Kong, C.S.; Lipecki, J.; Fishwick, K.J.; Odendaal, J.; Ewington, L.J.; et al. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun. Biol. 2020, 3, 37. [Google Scholar] [CrossRef] [Green Version]
- American College of Obstetricians and Gynecologists. Pregestational diabetes mellitus. ACOG Practice Bulletin No. 201. Obstet. Gynecol. 2018, 132, 1514–1516. [Google Scholar] [CrossRef] [PubMed]
- Meis, P.J.; Klebanoff, M.; Thom, E.; Dombrowski, M.P.; Sibai, B.; Moawad, A.H.; Spong, C.Y.; Hauth, J.C.; Miodovnik, M.; Varner, M.W.; et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N. Engl. J. Med. 2003, 348, 2379–2385. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blackwell, S.C.; Gyamfi-Bannerman, C.; Biggio, J.R., Jr.; Chauhan, S.P.; Hughes, B.L.; Louis, J.M.; Manuck, T.A.; Miller, H.S.; Das, A.F.; Saade, G.R.; et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG Study): A multicenter, international, randomized double-blind trial. Am. J. Perinatol. 2020, 37, 127–136. [Google Scholar] [CrossRef] [Green Version]
- Keelan, J.A. Intrauterine inflammatory activation, functional progesterone withdrawal, and the timing of term and preterm birth. J. Reprod. Immunol. 2018, 125, 89–99. [Google Scholar] [CrossRef]
- American College of Obstetricians and Gynecologists. Low-dose aspirin use during pregnancy. ACOG Committee Opinion No. 743. Obstet. Gynecol. 2018, 132, e44–e52. [Google Scholar] [CrossRef]
- Williams, P.J.; Bulmer, J.N.; Innes, B.A.; Broughton Pipkin, F. Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy. Biol. Reprod. 2011, 84, 1148–1153. [Google Scholar] [CrossRef]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ng, S.-W.; Norwitz, G.A.; Pavlicev, M.; Tilburgs, T.; Simón, C.; Norwitz, E.R. Endometrial Decidualization: The Primary Driver of Pregnancy Health. Int. J. Mol. Sci. 2020, 21, 4092. https://doi.org/10.3390/ijms21114092
Ng S-W, Norwitz GA, Pavlicev M, Tilburgs T, Simón C, Norwitz ER. Endometrial Decidualization: The Primary Driver of Pregnancy Health. International Journal of Molecular Sciences. 2020; 21(11):4092. https://doi.org/10.3390/ijms21114092
Chicago/Turabian StyleNg, Shu-Wing, Gabriella A. Norwitz, Mihaela Pavlicev, Tamara Tilburgs, Carlos Simón, and Errol R. Norwitz. 2020. "Endometrial Decidualization: The Primary Driver of Pregnancy Health" International Journal of Molecular Sciences 21, no. 11: 4092. https://doi.org/10.3390/ijms21114092