A5078668735- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Sexual Differentiation and Disorders
- Hormonal and reproductive studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Growth Hormone and Insulin-like Growth Factors
- Bioinformatics and Genomic Networks
- Estrogen and related hormone effects
- Microbial Metabolic Engineering and Bioproduction
- Gene Regulatory Network Analysis
- Birth, Development, and Health
- Lipid metabolism and biosynthesis
- Reproductive System and Pregnancy
- Endoplasmic Reticulum Stress and Disease
- Hypothalamic control of reproductive hormones
- Testicular diseases and treatments
- Reproductive Physiology in Livestock
- Circadian rhythm and melatonin
- Stress Responses and Cortisol
- Endometriosis Research and Treatment
- Ovarian function and disorders
- Hormonal Regulation and Hypertension
- Wnt/β-catenin signaling in development and cancer
- Mentoring and Academic Development
- Innovation and Knowledge Management
University of Edinburgh
2011-2021
MRC Centre for Reproductive Health
2011-2021
The Queen's Medical Research Institute
2010-2021
Zhejiang University-University of Edinburgh Institute
2021
University of Missouri–St. Louis
2020
Fontbonne University
2020
Moscow State University of Psychology & Education
2019
Roslin Institute
2016-2018
Ball State University
2001-2018
Medical Research Council
2011-2017
Phosphorylation of the conserved lipin Pah1p/Smp2p in Saccharomyces cerevisiae was previously shown to control transcription phospholipid biosynthetic genes and nuclear structure by regulating amount membrane present at envelope (Santos-Rosa, H., Leung, J., Grimsey, N., Peak-Chew, S., Siniossoglou, S. (2005) EMBO J. 24, 1931-1941). A recent report identified Pah1p as a Mg2+-dependent phosphatidate (PA) phosphatase that regulates de novo lipid synthesis (Han G.-S., Wu, W. I., Carman, G. M....
Changes in nuclear size and shape during the cell cycle or development require coordinated membrane remodeling, but underlying molecular events are largely unknown. We have shown previously that activity of conserved phosphatidate phosphatase Pah1p/Smp2p regulates structure yeast by controlling phospholipid synthesis biogenesis at envelope. Two screens for novel regulators led to identification DGK1. show Dgk1p is a unique diacylglycerol kinase uses CTP, instead ATP, generate phosphatidate....
Fetal growth plays a role in programming of adult cardiometabolic disorders, which men, are associated with lowered testosterone levels. and fetal androgen exposure can also predetermine levels although how is unknown, because the Leydig cells (ALCs) that produce do not differentiate until puberty. To explain this conundrum, we hypothesized stem for ALCs must be present testis might susceptible to by during masculinization. address hypothesis, used ALC ablation/regeneration identify that,...
Sertoli cells (SCs) regulate testicular fate in the differentiating gonad and are main regulators of spermatogenesis adult testis; however, their role during intervening period testis development, particular Leydig cell (ALC) differentiation function, remains largely unknown. To examine SC function fetal prepubertal development we generated two transgenic mouse models that permit controlled, cell-specific ablation SCs pre- postnatal life. Results show required: (1) to maintain differentiated...
Leydig cell number and function decline as men age, low testosterone is associated with all "Western" cardio-metabolic disorders. However, whether perturbed androgen action within the adult lineage predisposes individuals to this late-onset degeneration remains unknown. To address this, we generated a novel mouse model in which receptor (AR) ablated from ~75% of stem cell/cell progenitors, fetal life onward (Leydig AR knockout mice), permitting interrogation specific roles autocrine...
Abstract We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants high low familial risk for ASD watched dynamic videos spinning toys women singing nursery rhymes while high-density was recorded. Alpha functional (7–8 Hz) calculated using the debiased weighted phase lag index. The final sample clean...
BACKGROUND: Genes underlying circadian rhythm generation are expressed in many tissues. We explore a role for rhythms the timing and efficacy of mouse reproduction development using genetic approach. METHODS: compare fecundity ClockD19 mutant mice (a dominant-negative protein essential activity) Vipr2–/– null (affecting output hypothalamic suprachiasmatic nucleus) with wild type (WT) litter mates under both 12 h:12 h light:dark cycle continuous darkness. RESULTS: Uteri from show no...
Lipins are the founding members of a novel family Mg(2+)-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 activity regulated. Here we demonstrate functions lipin 1 2 evolutionarily conserved from unicellular eukaryotes to mammals. The two lipins display distinct intracellular localization HeLa M cells, with pool exhibiting tight membrane association. Small...
Abstract The epididymis plays an essential role in male fertility, and disruption of epididymal function can lead to obstructive azoospermia. Formation the is androgen-dependent. androgen receptor (AR) expressed both stromal epithelial compartments epididymis, action mediated via cells vital for its normal development function. However impact specific AR-dependent signaling remains underexplored. To address this, we used conditional gene-targeting mice selectively ablate AR from caput...
The Saccharomyces cerevisiae DGK1 gene encodes a diacylglycerol kinase enzyme that catalyzes the formation of phosphatidate from diacylglycerol. Unlike kinases bacteria, plants, and animals, yeast utilizes CTP, instead ATP, as phosphate donor in reaction. Dgk1p contains CTP transferase domain is present SEC59-encoded dolichol CDS1-encoded CDP-diacylglycerol synthase enzymes. Deletion analysis showed was sufficient for activity. Point mutations (R76A, K77A, D177A, G184A) conserved residues...
Problem Previous 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 study Generation CD 4+ 25+Foxp3+ regulatory T cells in Leydig cell‐conditioned media was determined by flow cytometry ELISA . Influence testosterone on cytokine response measured LPS ‐stimulated testicular macrophages, Sertoli peritubular cells. Results...
There is a need for formalised diagrams that both summarise current biological pathway knowledge and support modelling approaches explain predict their behaviour. Here, we present new, freely available framework includes biologist-friendly language (mEPN), simple but sophisticated method to model parameterisation using information; stochastic flow algorithm simulates the dynamics of activity; 3-D visualisation engine aids understanding complexities system’s dynamics. We example models...
The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by at specific time and in cell type. However, tamoxifen not an inert inducer recombination, but established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. Such potentially confounding effects should be controlled for, >40% publications that have used to generate conditional knockouts reported even minimum appropriate controls....
Androgens are known to be an essential regulator of male health. Androgen receptor (AR) is widely expressed throughout the adrenal cortex, yet wider role for androgen signalling in remains underexplored. To investigate AR-dependent and AR-independent adrenal, we used a novel mouse model with specific ablation cortex or without reduction circulating levels by castration. Our results describe AR expression human highlight that viable cortex. We show via required X-zone regression during...
Production of the androgen testosterone is controlled by a negative feedback loop within hypothalamic-pituitary-gonadal (HPG) axis. Stimulation testicular Leydig cells pituitary luteinising hormone (LH) under control hypothalamic gonadotrophin releasing (GnRH), while suppression LH secretion circulating testosterone. Exactly how androgens exert their (and whether this at level pituitary), as well role AR in other cell types remains unclear. To investigate these questions, we exploited...
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 endogenous Cytochrome P450 side chain cleavage enzyme (Cyp11a1) promoter. Mice Carrying Cyp11a1-GC (GFP-Cre) allele express fetal adrenal and testis, cortex, testicular Leydig cells (and small proportion Sertoli cells), theca ovary, hindbrain postnatal life. Circulating testosterone concentration is unchanged...
Rapid globalization of business processes stimulates many companies to dispatch their employees – expatriates on overseas assignments. Russia differs markedly from other cultures in terms specific communication norms and rules. Understanding such differences organizational life is crucial for the success working there. This study employs in-depth interviews with eight Danish who worked examines between Danes Russians characteristics related Hofstede's cultural dimension power distance. work...
The interstitium of the mouse testis contains Leydig cells and a small number steroidogenic with adrenal characteristics which may be derived from fetal during development or normal subset developing cells. Currently it is not known what regulates and/or proliferation this sub-population in testis. Androgen receptors (AR) are essential for testicular function study we have examined role AR regulating interstitial cell development. Using model lacks gonadotropins (hpg.ARKO), stimulation...
LKB1 acts as a master upstream protein kinase regulating number of kinases involved in diverse cellular functions. Recent studies have suggested role for male fertility. Male mice with reduced total expression, including the complete absence major splice variant testis (LKB1S), are completely infertile. We sought to further characterise these and determine mechanism underlying this infertility. This expression developing germ cells, morphological analysis mature spermatozoa histological both...
Androgen signalling is essential both for male development and function of the reproductive system in adulthood. Within adult testis, Germ cells (GC) do not express androgen receptor (AR) suggesting androgen-mediated promotion spermatogenesis must act via AR-expressing somatic cell-types. Several recent studies have exploited Cre/lox conditional gene-targeting to ablate AR from key cell-types order establish cell-specific role fertility. In this study, we used a similar approach specifically...
Adrenal androgens are fundamental mediators of ovarian folliculogenesis, embryonic implantation, and breast development. Although adrenal androgen function in target tissues well characterized, there is little research covering the role androgen-signaling within itself. glands express AR which essential for regression X-zone male mice. Female mice also undergo during their first pregnancy, however whether this controlled by signaling unknown. To understand receptor (AR) female adrenal, we...
BACKGROUND: The molecular basis of changes underlying the altered sensitivity uterine luminal epithelium (LE) to embryo over peri-implantation period is not fully understood. METHODS: Microarray analysis was performed on purified LE isolated from pseudo-pregnant mouse uterus at 12-h intervals pre-receptivity through implantation window refractoriness. aim identify genes whose expression in during this period. RESULTS: A total 447 transcripts were identified abundance changed more than 2-fold...