Searchable abstracts of presentations at key conferences on reproductive biology and medicine

ra0001p006 | Uterus | WCRB2014

Estrogen-dependent modulation of neuroinflammation in endometriosis

Greaves Erin , Horne Andrew W , Saunders Philippa T K

Introduction: Endometriosis is an estrogen-dependent inflammatory disorder, associated with debilitating pelvic pain. We believe the pain is due to neuroinflammation: growth of sensory neurons and their subsequent hypersensitisation by macrophage-derived cytokines within the lesion. We explored the regulation of neuroinflammation by estrogen receptor (ER) modulators.Materials and methods: Peritoneum and lesions were collected from women with and without ...

ra0001p273 | (1) | WCRB2014

Estradiol promotes differentiation of uterine natural killer cells during establishment of pregnancy

Gibson Douglas A , Critchley Hilary O D , Saunders Philippa T K

Background: Uterine natural killer (uNK) cells are a phenotypically distinct population of tissue-resident immune cells that are reported to regulate vascular remodelling within the endometrium. The mechanisms that control accumulation of uNK cells in the endometrium remain unresolved although there is evidence to suggest that homing and differentiation of peripheral blood NK (pbNK) cells may contribute to the rapid increase in cell numbers during the secretory phase of the me...

ra0001p304 | (1) | WCRB2014

The relaxing effect of dihydrotestosterone on myometrial smooth muscle contraction is mediated via blockage of intracellular calcium increase and inhibition of myosin light chain phosphorylation

Makieva Sofia , Saunders Philippa T K , Norman Jane E

Background: The impact of androgens on myometrial contraction has received less scrutiny, compared to progesterone and estrogens. We sought to i) examine the effect of dihydrotestosterone (DHT; a non-aromatizable androgen) on stretch-induced contraction of human myometrium and ii) gain mechanistic insights by studying changes in intracellular calcium [Ca2+] and phosphorylation of myosin light chain (MLC).Methods: Myometrial strips were recover...

ra0003o019 | SRF Student Prize Session | SRF2016

Immune cell dynamics in endometrial repair and remodelling

Kirkwood Phoebe , Cousins Fiona , Saunders Philippa , Gibson Douglas

Introduction: The endometrium is one of the few adult tissues that heals repeatedly without scarring. On a monthly basis the endometrium undergoes cyclical episodes of proliferation, degeneration, tissue repair and remodelling in response to the ‘injury’ inflicted on it during menstruation. In women, endometrial shedding (menses) is the culmination of a cascade of inflammatory signals between uterine stromal cells and immune cells both of which have key roles in endo...

ra0003p027 | (1) | SRF2016

Targeting lactate metabolism can be a novel therapeutic for the treatment of endometriosis

Ahmad Syed Furquan , Greaves Erin , Saunders Philippa , Horne Andrew

Introduction: Endometriosis is a chronic, hormone-dependent disorder characterized by the establishment and growth of endometrial tissue in extra-uterine sites, typically within the peritoneal cavity and causes debilitating pain. We have shown that peritoneal mesothelial cells recovered from the women with endometriosis have an altered energy metabolism with increased biosynthesis of lactate as a result of increased aerobic glycolysis. We hypothesize that ectopic endometrial t...

ra0001p274 | (1) | WCRB2014

A role for androgens in the regulation of endometrial breakdown and repair in a mouse model of menstruation

Cousins Fiona L , Murray Alison A , Critchley Hilary O D , Saunders Philippa T K

Background: The human endometrium is a dynamic, multi-cellular sex steroid-dependent tissue subject to cyclical episodes of breakdown (menses), repair and regeneration. The mechanisms responsible for initiation of menses are well characterised; the molecular and cellular changes responsible for rapid repair are poorly understood. Re-epithelialisation of the tissue is thought to involve contributions from both the stromal and epithelial compartments. A role for androgens in end...

ra0001p295 | (1) | WCRB2014

Investigating the role of androgens in endometriosis

Simitsidellis Ioannis , Greaves Erin , Collins Frances , Horne Andrew W , Saunders Philippa T K

Introduction: Androgen receptors (AR) have been detected in the human endometrium throughout the menstrual cycle and are reported to regulate expression of genes associated with cellular proliferation and cell-cycle regulation. Endometriosis is defined by establishment and growth of endometrial tissue in ectopic locations (typically on the peritoneal wall); patients often experience pain and infertility. In the current study we have used human tissue and a new mouse model of e...

ra0001p287 | (1) | WCRB2014

Short-term administration of ulipristal acetate modulates endometrial sex steroid receptor expression and cell proliferation markers

Murray Alison A , Shaw Grace G , Nicol Moira , Williams Alistair R W , Saunders Philippa T K , Critchley Hilary O D

Introduction: Uterine fibroids cause pain, pressure symptoms and heavy menstrual bleeding (HMB). Fibroid growth is sex steroid dependent. The selective progesterone receptor (PR) modulator (SPRM), ulipristal acetate (UPA) reduces fibroid size and alleviates HMB in 90% of women. UPA has both agonist and antagonist properties and induces (S)PRM-associated endometrial changes (PAEC). The mechanism of UPA action and aetiology of PAEC are unknown. We propose that modulation of ster...

ra0003o024 | Oral Communications 3: Environmental and programming effects on reproduction | SRF2016

Maternal protein restriction around conception alters the foetal mouse brain by reducing the neural stem cells and increasing neuronal differentiation during gestation, which might be associated with the adult behavioural deficits

Gould Joanna , Pearson-Farr Jenny , Airey Chris , Semmence Oliver , Gould Philippa , Willaime-Morawek Sandrine , Fleming Tom

Introduction: Maternal malnutrition during pregnancy is detrimental to fetal development and increases the risk of many chronic diseases in later life i.e. neurological consequences such as increased risk of schizophrenia. Previous studies have shown maternal protein malnutrition during pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical and pathway dynamics with lasting consequences for motor and cognitive...

ra0003o003 | Oral Communications 1: Ovary | SRF2016

PLCz-induced Ca2+ oscillations are enhanced after germinal vesicle breakdown during mouse oocyte maturation

Sanders Jessica , Bateson Ethan , Yu Yuansong , Nomikos Michail , Lai Antony , Swann Karl

Introduction: Mature mouse oocytes, arrested at meiotic metaphase II (MII), are activated by a series of Ca2+ oscillations caused by sperm-specific phospholipase C zeta (PLCz) which has been shown to localize in cytoplasmic vesicles. The substrate for PLCz, phosphatidylinositol 4,5-bisphosphate (PIP2), is also present in cytoplasmic vesicles in MII oocytes. Throughout oocyte maturation there is reported to be a gradual increase in sensitivity to PLCz and ...