Brianna Cloke | Search PubMed

PubMed2006

The uterine junctional zone.

Magnetic resonance imaging has revealed that the endometrio-myometrial interface constitutes a distinct, hormone-dependent uterine compartment termed the junctional zone. In the non-pregnant uterus, highly specialized contraction waves originate exclusively from the junctional zone and participate in the regulation of diverse reproductive events, such as sperm transport, embryo implantation, and menstrual shedding. Conversely, growing evidence suggests that disruption of the normal endometrio-myometrial interface plays an integral role in diverse reproductive disorders. This chapter reviews our current understanding of the mechanisms that govern the cyclic changes in the uterine junctional zone and summarizes the evidence implicating the endometrio-myometrial interface in normal uterine physiology and pathological processes.

Endometriosis↗

PubMed2006

Heparin prevents programmed cell death in human trophoblast.

Heparin is used clinically for the prevention of pregnancy complications associated with prothrombotic disorders, especially antiphospholipid antibody syndrome. Recent studies have suggested that heparin may exert direct effects on placental trophoblast, independently of its anticoagulant activity. We now demonstrate that heparin abrogates apoptosis of primary first trimester villous trophoblast in response to treatment with the pro-inflammatory cytokines interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. This multifunctional glycosaminoglycan also inhibited apoptosis induced by other agents, including staurosporin, broad-spectrum kinase inhibitor and thrombin. Furthermore, heparin attenuated caspase-3 activity, a hallmark of apoptosis, in human first trimester villous and extravillous trophoblast cell lines treated with peptidoglycan, a Toll-like receptor-2 agonist isolated from Staphylococcus aureus. The ability of heparin to antagonize cell death induced by such diverse apoptotic signals suggested that it acts as a survival factor for human trophoblast. We demonstrate that heparin, like epidermal growth factor (EGF) and heparin-binding EGF (HB-EGF), elicits phosphorylation of the EGF receptor and activation of the phosphatidyl inositol 3-kinase (PI3K)-, the extracellular signal-related kinase 1/2 (ERK1/2)- and the c-Jun NH2 terminal kinase (JNK)-signal transduction pathways in primary villous trophoblast. In summary, we have demonstrated that heparin activates multiple anti-apoptotic pathways in human trophoblast. Our results suggest that heparin may be useful in the management of at-risk patients, even in the absence of an identifiable thrombophilic disorder.

Apoptosis↗