Reproductive health is crucial to successful conception, pregnancy and delivery. Globally, 15 million babies are born before they are 'ready' and within the UK, preterm birth accounts for ~8% of all deliveries.
High profile conditions such as gestational diabetes and obesity in pregnancy pose new challenges. Thus, there is a need for early diagnosis, prevention and cure of several pregnancy specific disorders as current clinical treatments are limited or non-existent.
A better scientific understanding of the biological mechanisms that determine reproductive outcomes is an important goal.
We use a variety of techniques (electrophysiology, myography, molecular, immunochemical and analytical methods) to investigate key molecules and mechanisms in pregnancy involved in the regulation of vascular function, role of inflammation and the transition from gestational quiescence to parturition.
What we are doing about...
1. Preterm labour
Although the triggers for both term and preterm labour are not known, switches in expression and function of proteins that favour a contractile phenotype are thought to be activated too early.
We have previously described changes in myometrial and decidual ion channels with the onset of labour that highlight the complex regulation of uterine function. Our current work is focussed on the role of ion channels, inflammatory mediators and lipids to identify potentially new means of detecting and treating preterm labour.
This condition, characterised by hypertension and proteinuria, is present in 1-5% of pregnant women.
It originates in early pregnancy but symptoms present much later. Pre-eclampsia is a multi-system disorder that can affect the mother, her baby or both and may be associated with the development of cardiovascular disease in later life. Research in our lab is underway on comparing vascular and immune function in the placentae of pre eclamptic and normal women.
Approximately 1 in 7 couples seek advice for infertility. For some 25% of these infertile cases, there is no known explanation.
The endometrium provides a favourable environment to facilitate implantation however there is only limited information on the physiological factors within the endometrial milieu that determine receptivity. We have begun studies investingating loca factor within the human endometrium that may play a role in successful pregnancy outcome by coupling to membrane proteins modulated by, for example pH, oxygen levels, stretch and local mediators.
- Mechanisms regulating production of proinflammatory mediators in labour and preterm labour
- Role of non-prostanoid eicosanoid modulation of vascular function in normal and pre-eclamptic pregnancies
- Ion channels in endometrial function
- The insulin signalling pathway in adipocytes of women with and without polycystic ovarian syndrome
- Control of myometrial contractility
Our research has led to publications in leading peer-reviewed journals. Find out more from the individual group member's profile.
- Webster, S. J., Waite, S. L., Cookson, V. J., Warren, A., Khan, R., Gandhi, S. V., Europe-Finner, G. N. and Chapman, N. R. (2013). Regulation of GTP-binding Protein (Gas) Expression in Human Myometrial Cells: A Role for Tumour Necrosis Factor in Modulating Gas Promoter Acetylation by Transcriptional Complexes. J. Biol. Chem. 288: 6704-6716.
- Patel SK, Jackson LJ, Warren AY, Shaw RW, Khan RN (2013) A role for two-pore potassium (K2P) channels in endometrial epithelial function J Cell Mol Med 17, 134-146
- Pang V, Counillon L, Lagadic-Gossmann D, Poet M, Lacroix J, Sergent O, Khan R, Rauch C (2012). On the role of the difference in surface tensions involved in the allosteric regulation of NHE-1 induced by low to mild osmotic pressure, membrane tension and lipid asymmetry. Cell Biochem Biophys. 2012 63:47-57. doi: 9340-9347.
- Alcock J, Warren AY, Goodson YJ, Hill SJ, Khan RN, Lymn JS (2011). Inhibition of tissue transglutaminase II attenuates contractility of pregnant human myometrium. Biol Reprod 84, 646-653. Epub 2010 Dec 1.
- Pearson T, Zhang J, Arya P, Warren AY, Ortori C, Fakis A, Khan RN, Barrett DA (2010) Measurement of vasoactive metabolites (hydroxyeicosatetraenoic and epoxyeicosatrienoic acids) in uterine tissues of normal and compromised human pregnancy. Journal of Hypertension 28, 2429-2437
- Pearson T, Warren AY, Barrett DA, Khan RN (2009) Detection of EETs and HETE-generating cytochrome P-450 enzymes and the effects of their metabolites on myometrial and vascular function. American Journal of Physiology- Endocrinology and Metabolism 297, E647-656
- Khan RN, Matharoo-Ball B, Shaw RW (2009) Antioxidant enzyme expression, lipid peroxidation, and protein oxidation in human myometrium with parturition. Reproductive Sciences 17, 78-84
- Warren AY, Harvey L, Shaw RW, Khan RN (2008) Interleukin-1 beta secretion from cord blood mononuclear cells in vitro involves P2X7 receptor activation. Reproductive Sciences 15,189-194
- Liu B, Hill SJ, Khan RN (2005) Oxytocin inhibits T-type calcium current of human decidual stromal cells. Journal Clinical Endocrinology and Metabolism 90, 4191-4197
- Chanrachakul B, Broughton Pipkin F, Khan RN (2004) Contribution of coupling between human myometrial 2-adrenoreceptor and the BKCa channel to uterine quiescence. American Journal of Physiology-Cell Physiology 287, C1747-C1752
- Khan RN, Matharoo-Ball B, Arulkumaran S. Ashford MLJ (2001) Potassium channels in the human myometrium. Experimental Physiology 86, 255-264