Laura O'Hara

Laura O'Hara
The University of Edinburgh | UoE · Centre for Integrative Physiology

PhD

About

51
Publications
8,510
Reads
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1,546
Citations
Citations since 2016
29 Research Items
1002 Citations
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
Additional affiliations
January 2018 - present
The University of Edinburgh
Position
  • Lecturer
Description
  • University of Edinburgh/University of Zhejiang
August 2013 - August 2015
The University of Edinburgh
Position
  • PostDoc Position
April 2011 - December 2017
The University of Edinburgh
Position
  • Fellow
Education
September 2007 - March 2011

Publications

Publications (51)
Article
Full-text available
There is a need for formalised diagrams that both summarise current biological pathway knowledge and support modelling approaches that explain and predict their behaviour. Here, we present a new, freely available modelling framework that includes a biologist-friendly pathway modelling language (mEPN), a simple but sophisticated method to support mo...
Article
Full-text available
Androgens such as testosterone are steroid hormones essential for normal male reproductive development and function. Mutations of androgen receptors (AR) are often found in patients with disorders of male reproductive development, and milder mutations may be responsible for some cases of male infertility. Androgens exert their action through AR and...
Article
Full-text available
Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is contro...
Article
Full-text available
Leydig cell number and function decline as men age, and low testosterone is associated with all "Western" cardio-metabolic disorders. However, whether perturbed androgen action within the adult Leydig cell lineage predisposes individuals to this late-onset degeneration remains unknown. To address this, we generated a novel mouse model in which andr...
Article
Full-text available
To permit conditional gene targeting of floxed alleles in steroidogenic cell-types we have generated a transgenic mouse line that expresses Cre Recombinase under the regulation of the endogenous Cytochrome P450 side chain cleavage enzyme (Cyp11a1) promoter. Mice Carrying the Cyp11a1-GC (GFP-Cre) allele express Cre Recombinase in fetal adrenal and t...
Article
Background : Circulating prolactin concentration in rodents and humans is sexually dimorphic. Estrogens are a well‐characterised stimulator of prolactin release. Circulating prolactin fluctuates throughout the menstrual/estrous cycle of females in response to estrogen levels, but remains continually low in males. We have previously identified andro...
Article
Full-text available
The epididymis is an androgen-responsive organ, whose structure and functions are modulated by the coordination between androgen and epididymal cues. Highly-regulated molecular interaction within the epididymis is required to support viable sperm development necessary for subsequent fertilization. In the present study, we extended our earlier findi...
Article
Full-text available
Adrenal androgens are fundamental mediators of ovarian folliculogenesis, embryonic implantation, and breast development. Although adrenal androgen function in target tissues are well characterized, there is little research covering the role of androgen-signaling within the adrenal itself. Adrenal glands express AR which is essential for the regress...
Article
Full-text available
The anterior and intermediate lobes of the pituitary are composed of endocrine cells, vasculature and supporting cells, such as folliculostellate cells. Folliculostellate cells form a network with several postulated roles in the pituitary, including production of paracrine signalling molecules and cytokines, coordination of endocrine cell hormone r...
Preprint
Circulating prolactin concentration in rodents and humans is sexually dimorphic. Estrogens are a well-characterised stimulator of prolactin release. Circulating prolactin fluctuates throughout the menstrual/estrous cycle of females in response to estrogen levels, but remains continually low in males. We have previously identified androgens as an in...
Article
Full-text available
Androgens are known to be an essential regulator of male health. Androgen receptor (AR) is widely expressed throughout the adrenal cortex, yet the wider role for androgen signalling in the adrenal remains underexplored. To investigate AR-dependent and AR-independent androgen signalling in the adrenal, we used a novel mouse model with a specific abl...
Article
Full-text available
Background The interstitium of the mouse testis contains Leydig cells and a small number of steroidogenic cells with adrenal characteristics which may be derived from the fetal adrenal during development or may be a normal subset of the developing fetal Leydig cells. Currently it is not known what regulates development and/or proliferation of this...
Article
Full-text available
The hypothalamic-pituitary-adrenal (HPA) axis regulates responses to internal and external stressors. Many patients diagnosed with conditions such as depression or anxiety also have hyperactivity of the HPA axis. Hyper-stimulation of the HPA axis results in sustained elevated levels of glucocorticoids which impair neuronal function and can ultimate...
Article
Full-text available
Objective: Steroid hormones are responsible for the control of a wide range of physiological processes such as development, growth, reproduction, metabolism, and aging. Because of the variety of enzymes, substrates and products that take part in steroidogenesis and the compartmentalisation of its constituent reactions, it is a complex process to v...
Article
Full-text available
A major endeavor of systems biology is the construction of graphical and computational models of biological pathways as a means to better understand their structure and function. Here, we present a protocol for a biologist-friendly graphical modeling scheme that facilitates the construction of detailed network diagrams, summarizing the components o...
Chapter
Spermatogenesis, the process essential for male fertility, relies on the continuous supply of differentiating germ cells from a pool of spermatogonial stem cells. Spermatogenesis is dependent upon hormonal stimuli that result in a complex pattern of intratesticular signalling pathways. The two main hormones responsible for its control are pituitary...
Article
Full-text available
The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by Cre at a specific time and in a specific cell type. However, tamoxifen is not an inert inducer of recombination, but an established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. S...
Chapter
The androgen testosterone has an essential trophic role in the development of male physiology and in adult spermatogenesis and fertility. Testosterone mainly exerts its effect through the androgen receptor (AR), a ligand-Activated transcription factor that is activated by binding the androgens testosterone or dihydrotestosterone. Mutations in AR ca...
Chapter
This revised and updated second edition provides a comprehensive account of the human male gamete. Detailed overviews of human sperm production, maturation, and function - and how these processes affect and influence fertility, infertility, and assisted reproduction - are given. A wide range of new developments including proteomics, spermatogenesis...
Preprint
Full-text available
In silico modelling of biological pathways is a major endeavour of systems biology. Here we present a methodology for construction of pathway models from the literature and other sources using a biologist-friendly graphical modelling system. The pathway notation scheme, called mEPN, is based on the principles of the process diagrams and Petri nets,...
Chapter
Conditional gene targeting has revolutionized molecular genetic analysis of nuclear receptor proteins, however development and analysis of such conditional knockouts is far from simple, with many caveats and pitfalls waiting to snare the novice or unprepared. In this chapter, we describe our experience of generating and analyzing mouse models with...
Poster
Androgens bind to their cognate androgen receptor (AR), which acts as a transcription factor to regulate gene expression essential for the development and maintenance of male sexual characteristics. Androgens may also play an important role in adrenal development by suppressing the rodent x-zone in postnatal life (1), though the mechanism underpinn...
Article
ProblemPrevious studies demonstrated a strong association between low androgen levels and reduced capacity to mount an inflammatory response. However, the mechanisms underlying these observations are largely not understood.Methods of studyGeneration of CD4+CD25+Foxp3+ regulatory T cells in Leydig cell-conditioned media was determined by flow cytome...
Poster
Androgen receptor (AR) is expressed by testicular somatic cells including steroidogenic Leydig cells (LC). Its role in LC is ill defined, with hypotheses based on evidence from total androgen receptor knockout models implying that LC AR is responsible for final LC number, regulation of steroidogenic enzyme expression and LC maturation. To better de...
Article
Full-text available
Sertoli cells (SCs) regulate testicular fate in the differentiating gonad and are the main regulators of spermatogenesis in the adult testis; however, their role during the intervening period of testis development, in particular during adult Leydig cell (ALC) differentiation and function, remains largely unknown. To examine SC function during fetal...
Article
Full-text available
Significance Men are defined by androgens (testosterone), which drive fetal masculinization (male development) and puberty and maintain masculinity in adulthood, including sex drive, erectile function, and fertility. Moreover, Western cardiometabolic diseases are all associated with lowered testosterone levels in men. Therefore, influences on testo...
Article
Full-text available
Androgen signalling is essential both for male development and function of the male reproductive system in adulthood. Within the adult testis, Germ cells (GC) do not express androgen receptor (AR) suggesting androgen-mediated promotion of spermatogenesis must act via AR-expressing somatic cell-types. Several recent studies have exploited the Cre/lo...
Article
Full-text available
LKB1 acts as a master upstream protein kinase regulating a number of kinases involved in diverse cellular functions. Recent studies have suggested a role for LKB1 in male fertility. Male mice with reduced total LKB1 expression, including the complete absence of the major splice variant in testis (LKB1(S)), are completely infertile. We sought to fur...
Thesis
Androgen receptor (AR) signalling is essential for the development and function of the male reproductive system. Conditional gene ablation using the Cre-loxP system has previously assisted in the elucidation of the role of AR in different cell types. The aim of this study was to examine the effects of the ablation of AR in previously untargeted cel...
Article
Full-text available
The epididymis plays an essential role in male fertility, and disruption of epididymal function can lead to obstructive azoospermia. Formation and function of the epididymis is androgen-dependent. The androgen receptor (AR) is expressed in both the stromal and epithelial compartments of the epididymis, and androgen action mediated via stromal cells...
Article
Full-text available
Lipins are the founding members of a novel family of Mg2+-dependent phosphatidate phosphatases (PAP1 enzymes) that play key roles in fat metabolism and lipid biosynthesis. Despite their importance, there is still little information on how their activity is regulated. Here we demonstrate that the functions of lipin 1 and 2 are evolutionarily conserv...
Article
Full-text available
Changes in nuclear size and shape during the cell cycle or during development require coordinated nuclear membrane remodeling, but the underlying molecular events are largely unknown. We have shown previously that the activity of the conserved phosphatidate phosphatase Pah1p/Smp2p regulates nuclear structure in yeast by controlling phospholipid syn...
Article
Full-text available
The Saccharomyces cerevisiae DGK1 gene encodes a diacylglycerol kinase enzyme that catalyzes the formation of phosphatidate from diacylglycerol. Unlike the diacylglycerol kinases from bacteria, plants, and animals, the yeast enzyme utilizes CTP, instead of ATP, as the phosphate donor in the reaction. Dgk1p contains a CTP transferase domain that is...
Article
Full-text available
Phosphorylation of the conserved lipin Pah1p/Smp2p in Saccharomyces cerevisiae was previously shown to control transcription of phospholipid biosynthetic genes and nuclear structure by regulating the amount of membrane present at the nuclear envelope (Santos-Rosa, H., Leung, J., Grimsey, N., Peak-Chew, S., and Siniossoglou, S. (2005) EMBO J. 24, 19...
Article
Full-text available
The molecular basis of changes underlying the altered sensitivity of the uterine luminal epithelium (LE) to the embryo over the peri-implantation period is not fully understood. Microarray analysis was performed on purified LE isolated from the pseudo-pregnant mouse uterus at 12-h intervals from pre-receptivity through the implantation window to re...
Article
Full-text available
Genes underlying circadian rhythm generation are expressed in many tissues. We explore a role for circadian rhythms in the timing and efficacy of mouse reproduction and development using a genetic approach. We compare fecundity in Clock(Delta19) mutant mice (a dominant-negative protein essential for circadian rhythm activity) and in Vipr2-/- null m...

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Projects (2)
Project
The role of androgen receptor in the male reproductive and endocrine systems