Roles of Two Small Leucine-Rich Proteoglycans Decorin and Biglycan in Pregnancy and Pregnancy-Associated Diseases

Two small leucine-rich proteoglycans (SLRP), decorin and biglycan, play important roles in structural–functional integrity of the placenta and fetal membranes, and their alterations can result in several pregnancy-associated diseases. In this review, we briefly discuss normal placental structure and functions, define and classify SLRPs, and then focus on two SLRPs, decorin (DCN) and biglycan (BGN). We discuss the consequences of deletions/mutations of DCN and BGN. We then summarize DCN and BGN expression in the pregnant uterus, myometrium, decidua, placenta, and fetal membranes. Actions of these SLRPs as ligands are then discussed in the context of multiple binding partners in the extracellular matrix and cell surface (receptors), as well as their alterations in pathological pregnancies, such as preeclampsia, fetal growth restriction, and preterm premature rupture of membranes. Lastly, we raise some unanswered questions as food for thought.

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A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin

Reproduction ◽

10.1530/rep-10-0387 ◽

2011 ◽

Vol 142 (1) ◽

pp. 183-194 ◽

Cited By ~ 21

Author(s):

Megan L Calmus ◽

Elyse E Macksoud ◽

Richard Tucker ◽

Renato V Iozzo ◽

Beatrice E Lechner

Keyword(s):

Preterm Birth ◽

Fetal Membranes ◽

Dependent Manner ◽

Null Mutant ◽

Wild Type ◽

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Ehlers Danlos Syndrome ◽

Genetic Ablation ◽

Preterm Premature Rupture

Preterm premature rupture of membranes is responsible for one-third of preterm births. Ehlers–Danlos syndrome (EDS) is associated with preterm premature rupture of membranes in humans. In particular, an EDS variant is caused by a genetic mutation resulting in abnormal secretion of biglycan and decorin, two small leucine-rich proteoglycans highly expressed in reproductive tissues. Because biglycan/decorin null mutant (Bgn−/−Dcn−/−) mice demonstrate phenotypic changes similar to EDS, we used this model to test whether either biglycan or decorin or both play a role in the attainment of successful term gestation. Wild-type biglycan null mutant, decorin null mutant, and biglycan/decorin null mutant pregnancies were assessed for the length of gestation, pup and placenta weight, and litter size. Quantitative real-time PCR was performed to measure biglycan and decorin gene expression, and immunohistochemistry was performed to assess protein expression in placenta and fetal membranes at embryonic days E12, E15, and E18.Bgn−/−Dcn−/−dams displayed preterm birth, whereas the possession of at least two biglycan or decorin wild-type alleles was protective of preterm birth. The number ofBgn−/−Dcn−/−pups was decreased at postnatal day P1 but not at E18. Biglycan and decorin were upregulated in the placenta in the absence of each other and were developmentally regulated in fetal membranes, suggesting that these two proteoglycans demonstrate genetic complementation and contribute to gestational success in a dose-dependent manner. Thus, the biglycan/decorin null mutant mouse is a model of genetically induced preterm birth and perinatal loss. This model presents novel targets for preventive or therapeutic manipulation of preterm birth.

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Apoptosis in the Chorion of Fetal Membranes in Preterm Premature Rupture of Membranes

American Journal of Perinatology ◽

10.1055/s-2007-1004828 ◽

2008 ◽

Vol 25 (1) ◽

pp. 029-032 ◽

Cited By ~ 24

Author(s):

Ronald George ◽

Jennifer Kalich ◽

Bryan Yonish ◽

Amy Murtha

Keyword(s):

Fetal Membranes ◽

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Preterm Premature Rupture

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Interleukin-10 inhibition of gelatinases in fetal membranes: therapeutic implications in preterm premature rupture of membranes

Obstetrics and Gynecology ◽

10.1016/s0029-7844(01)01441-7 ◽

2001 ◽

Vol 98 (2) ◽

pp. 284-288 ◽

Cited By ~ 11

Author(s):

S Fortunato

Keyword(s):

Interleukin 10 ◽

Fetal Membranes ◽

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Therapeutic Implications ◽

Preterm Premature Rupture

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Visualisation of the insertion of a membrane for the treatment of preterm rupture of fetal membranes using a synthetic model of a pregnant uterus

Journal of Biomaterials Applications ◽

10.1177/0885328218786038 ◽

2018 ◽

Vol 33 (2) ◽

pp. 234-244

Author(s):

Sabiniano Roman ◽

Christopher Hillary ◽

Brenda Narice ◽

Anthony J Bullock ◽

Dilly OC Anumba ◽

...

Keyword(s):

Mechanical Properties ◽

Amniotic Fluid ◽

Bilayer Membrane ◽

Fetal Membrane ◽

Fetal Membranes ◽

Premature Rupture ◽

Management Options ◽

Pregnant Uterus ◽

Fetal Survival ◽

Preterm Premature Rupture

Preterm premature rupture of fetal membranes is a leading cause of preterm delivery. Preterm labour can compromise fetal survival, and even if a pregnancy affected by preterm premature rupture of fetal membrane continues, major complications associated with leakage of amniotic fluid and risk of infection can affect the normal development and survival of the baby. There are limited management options for preterm premature rupture of fetal membrane other than delivery of the baby if ascending infection (chorioamnionitis) is suspected. We have previously reported the development and characterisation of an implantable membrane with the aim of using it to occlude the internal os of the cervix, in order to prevent amniotic fluid loss, allow fluid reaccumulation and reduce the risk of chorioamnionitis. For this, an electrospun biocompatible and distensible bilayer membrane was designed with mechanical properties similar to the human amniotic membrane. In this study, we consider the effects of sterilization on the membrane, how to insert the membrane and visualise it using routine clinical methods. To do this, we used e-beam sterilisation and examined the ability of the membrane to adhere to ex vivo human cervical tissues. We also studied its insertion into a custom-synthesised model of a 20-week pregnant uterus and imaged the membrane using ultrasound. Sterilisation produced minor effects on physical and mechanical properties, but these did not affect the capacity of the membrane to be sutured or to provide a fluid barrier. We demonstrated that fibrin glue can successfully adhere the bilayer membrane to cervical tissues. Finally, we demonstrated that the membrane can be inserted through the cervix as well as visualized in place using ultrasound imaging and an endoscope. In summary, we suggest this membrane is a candidate for further development in an appropriate animal model, supported by appropriate imaging, to precede possible future human studies if judged to demonstrate satisfactory safety and efficacy profiles.

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Preterm Premature Rupture of Membranes in Twins: Comparison of Rupture in the Presenting Versus Non-presenting Sac

Journal of Obstetrics and Gynaecology Canada ◽

10.1016/j.jogc.2019.06.016 ◽

2020 ◽

Vol 42 (2) ◽

pp. 163-168 ◽

Cited By ~ 1

Author(s):

Elad Mei-Dan ◽

Zoe Hutchison ◽

Mark Osmond ◽

Susan Pakenham ◽

Eugene Ng ◽

...

Keyword(s):

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Preterm Premature Rupture

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Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) – Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and the Management of Preterm Premature Rupture of Membranes

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0903-2735 ◽

2019 ◽

Vol 79 (08) ◽

pp. 813-833 ◽

Cited By ~ 2

Author(s):

Richard Berger ◽

Harald Abele ◽

Franz Bahlmann ◽

Ivonne Bedei ◽

Klaus Doubek ◽

...

Keyword(s):

Preterm Birth ◽

German Society ◽

Consensus Conference ◽

Tertiary Prevention ◽

Short Version ◽

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Preterm Premature Rupture ◽

Gynecology And Obstetrics ◽

Self Help Groups

Abstract Aims This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups. Methods The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus). Recommendations Part 2 of this short version of the guideline presents Statements and Recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

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Neonatal lymphocyte subpopulations analysis and maternal preterm premature rupture of membranes: a pilot study

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0375 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Margherita Amadi ◽

Silvia Visentin ◽

Francesca Tosato ◽

Paola Fogar ◽

Giulia Giacomini ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

T Cell ◽

T Helper Cells ◽

Lymphocyte Subpopulations ◽

T Helper ◽

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Preterm Premature Rupture ◽

Helper Cells

Abstract Objectives Preterm premature rupture of membranes (pPROM) causes preterm delivery, and increases maternal T-cell response against the fetus. Fetal inflammatory response prompts maturation of the newborn’s immunocompetent cells, and could be associated with unfavorable neonatal outcome. The aims were to examine the effects of pPROM (Mercer BM. Preterm premature rupture of the membranes: current approaches to evaluation and management. Obstet Gynecol Clin N Am 2005;32:411) on the newborn’s and mother’s immune system and (Test G, Levy A, Wiznitzer A, Mazor M, Holcberg G, Zlotnik A, et al. Factors affecting the latency period in patients with preterm premature rupture of membranes (pPROM). Arch Gynecol Obstet 2011;283:707–10) to assess the predictive value of immune system changes in neonatal morbidity. Methods Mother-newborn pairs (18 mothers and 23 newborns) who experienced pPROM and controls (11 mothers and 14 newborns), were enrolled. Maternal and neonatal whole blood samples underwent flow cytometry to measure lymphocyte subpopulations. Results pPROM-newborns had fewer naïve CD4 T-cells, and more memory CD4 T-cells than control newborns. The effect was the same for increasing pPROM latency times before delivery. Gestational age and birth weight influenced maturation of the newborns’ lymphocyte subpopulations and white blood cells, notably cytotoxic T-cells, regulatory T-cells, T-helper cells (absolute count), and CD4/CD8 ratio. Among morbidities, fewer naïve CD8 T-cells were found in bronchopulmonary dysplasia (BPD) (p=0.0009), and more T-helper cells in early onset sepsis (p=0.04). Conclusions pPROM prompts maturation of the newborn’s T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.

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