Roger G Sturmey

Hull York Medical School · Medicine

A number of factors may impinge on thermal homeostasis in the early embryo. The most obvious is the ambient temperature in which development occurs. Physiologically, the temperature in the lumen of the female tract is typically lower than the core body temperature, yet rises at ovulation in the human, while in an IVF setting, embryos are usually ma...

Protein O-GlcNAcylation, a dynamic and reversible glucose-dependent post-translational modification of serine and threonine residues on target proteins, has been proposed to promote vascular smooth muscle cell proliferation and migration events implicated in vein graft failure (VGF). Therefore, targeting the enzymes (glutamine fructose-6P amidotran...

Introduction Clinical data suggest that over 70% of patients with Type 2 diabetes mellitus (T2DM) will die of cardiovascular diseases (CVD). T2DM patients with saphenous vein coronary artery bypass grafts are also prone to vein graft failure within 10 years, a phenomenon which arises from alterations in human saphenous vein smooth muscle cell (HSV-...

This article revisits the hypothesis, proposed in 2002, that the successful development of oocytes and preimplantation mammalian embryos is associated with a metabolism which is “quiet” rather than “active”, within limits which had yet to be defined. A distinction was drawn between Functional Quietness, Loss of quietness in response to stress and I...

Amino acids are now recognised as having multiple cellular functions in addition to their traditional role as constituents of proteins. This is well-illustrated in the early mammalian embryo where amino acids are now known to be involved in intermediary metabolism, as energy substrates, in signal transduction, osmoregulation and as intermediaries i...

The use of in vitro embryo production in the horse is increasing in clinical and research settings, however, protocols are yet to be optimised. Notably, the two most commonly used base media for in vitro maturation (IVM) supply glucose at markedly different concentrations: physiological (5.6 mM, M199) or supraphysiological (17 mM, DMEM/F-12). Expos...

Mitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific m...

Numerical data in biology and medicine are commonly presented as mean or median with error or confidence limits, to the exclusion of individual values. Analysis of our own and others’ data indicates that this practice risks excluding ‘Goldilocks’ effects in which a biological variable falls within a range between ‘too much’ and ‘too little’ with a...

Selection of the most viable embryo to transfer and at which stage of development remains one of the most challenging aspects of in vitro fertilization. There is little consensus regarding the observations to make and how frequently to record them. Many schemes use a combination of criteria, including the addition of pronuclear morphological scores...

Background: Assisted reproduction technology offers the opportunity to observe the very early stages of human development. However, due to practical constraints, for decades morphological examination of embryo development has been undertaken at a few isolated time points at the stages of fertilisation (Day 1), cleavage (Day 2-3) and blastocyst (Da...

Background: Mitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated t...

androgen aneuploidy antral follicles assessment assisted hatching assisted reproductive technology blastocyst blastocyst stage catheter chromosome cleavage stage clinical pregnancy rate cryopreservation culture media DHEA donor dose effect embryo culture embryo development embryo transfer Fertil Steril follicular follitropin alfa genetic GnRH agoni...

The objective of this study was to examine the effect of intravenous infusion of glucose on early embryonic development in lactating dairy cows. Nonpregnant, lactating dairy cows (n = 12) were enrolled in the study (276 ± 17 d in milk). On d 7 after a synchronized estrus, cows were randomly assigned to receive an intravenous infusion of either 750...

Approximately 65–75 days post-partum (dpp), the estrous cycles of non-lactating (dried off immediately post partum: n = 12) and lactating (n = 13) Holstein Friesian cows were synchronized and on Day 7 a single blastocyst derived from superovulated nulliparous Holstein Friesian heifers was transferred to each cow. A control group of nulliparous heif...

The aim of this study was to test the hypothesis that the metabolic stresses associated with lactation alter the ability of the endometrium to respond appropriately to the conceptus by examining endometrial gene expression on Day 19 of pregnancy. Immediately after calving, primiparous Holstein cows with similar production and fertility estimated br...

The dietary derived isoflavone and oestrogen analogue, genistein, is known to perturb fundamental reproductive events such as implantation and embryo cleavage. However the question of whether genistein is able to traverse the oviduct epithelial monolayer and impact oviduct fluid secretion remains unclear. This study tests these research questions u...

We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24h-treatments at day 9: 1) CONTROL (0µM NEFA + 0%EtOH), 2) SOLVENT CONTROL (0µM NEFA + 0.45%EtOH), 3) BASAL NEFA (720µM NEFA + 0.45%EtOH in the...

Knowledge of the biochemical composition of the bovine oviduct in the presence of an embryo is lacking. We have recently reported the detection of alterations to the bovine oviduct transcriptome when multiple embryos, but not a single embryo, were present (Maillo et al. 2015 Biol. Reprod. 92, 144). Thus, we hypothesised that the presence of an embr...

Oviduct fluid is the microenvironment that supports early reproductive processes including fertilisation, embryo cleavage, and genome activation. However, the composition and regulation of this critical environment remains rather poorly defined. This study uses an in vitro preparation of the bovine oviduct epithelium, to investigate the formation a...

In cattle, maternal recognition of pregnancy occurs on Day 16 via secretion of interferon tau (IFNT) by the conceptus. The endometrium can distinguish between embryos with different developmental competencies. In eutherian mammals, X-chromosome inactivation (XCI) is required to ensure an equal transcriptional level of most X-linked genes for both m...

The quiet embryo hypothesis postulates that early embryo viability is associated with a relatively low metabolism (Leese. 2002. BioEssays 24: 845-849). This proposal is re-visited here using retrospective and prospective data on the metabolic activity and kinetics of preimplantation development alongside the concept that an optimal range of such in...

The epithelium lining the oviduct/fallopian tube is critical for early reproductive events, many of which are mediated via intracellular calcium ions. Despite this, little is known about the regulation of calcium homeostasis in the oviductal epithelium. Epithelial Transient Receptor Potential Channels (TRPCs) modulate calcium flux in other tissues...

Tissue and whole organ regeneration is a dramatic biological response to injury that occurs across different plant and animal phyla. It frequently requires the dedifferentiation of mature cells to a condensed mesenchymal blastema, from which replacement tissues develop. Human somatic cells cannot regenerate in this way and differentiation is consid...

The advent of metabolomics technology and its application to small samples has allowed us to non-invasively monitor the metabolic activity of embryos in a complex culture environment. The aim of this study was to apply metabolomics technology to the analysis of individual embryos from several species during in vitro development to gain an insight i...

Study question: Is the developmental timing and metabolic regulation disrupted in embryos from overweight or obese women? Summary answer: Oocytes from overweight or obese women are smaller than those from women of healthy weight, yet post-fertilization they reach the morula stage faster and, as blastocysts, show reduced glucose consumption and e...

Oviduct luminal fluid supports early embryo development. The composition this fluid has been debated despite studies using post mortem samples and direct sampling under anesthesia. The routine availability of such data would benefit in vitro embryo culture in addition to our understanding of the influences of maternal physiology on in vivo oviduct...

In cattle, conceptus-maternal interactions are critical for the establishment and maintenance of pregnancy. A major component of this early interaction involves the transport of nutrients and secretion of key molecules by uterine epithelial cells to help support conceptus development during the peri-implantation period of pregnancy. Objectives were...

BACKGROUND Most tissues in the body rely on the presence of gap junctions in order to couple their component cells electrically and metabolically via intercellular transport of ions, metabolites and signalling agents. As a result, cells within tissues achieve a high degree of, ‘metabolic homogeneity’ which enables them to develop in an integrated w...

ContentsIn many countries, fat supplementation in the diet has become common in the dairy industry. There are several ideas as to how dietary fat could influence reproductive performance. Saturated fatty acids, such as palm oil, can increase milk yield but may aggravate negative energy balance and thus may impair fertility when fed during the first...

Non-invasive assay of the consumption and release of metabolites by individual human embryos could allow selection at the cleavage stage of development and facilitate Single Embryo Transfer in clinical IVF but will require simple, high throughput, sensitive methods applicable to small volume samples. A rapid, simple, non-invasive method has therefo...

Comparison of mean values of AA consumed or produced in culture media between embryos with or without evidences of morphological changes after 24 hours of individual culture. (DOC)

Comparison of mean values of AA consumed or produced in culture media by individual bovine embryos produced in vitro . (DOC)

The practice of "fat feeding" has become common in the dairy industry in a number of countries. There are several ideas as to how dietary lipids could influence reproductive performance. Highly saturated triacylglycerols (TAG), like palm oil, can increase milk yield but may aggravate negative energy balance and consequently impair fertility when fe...

A key characteristic of cancer cells is the ability to switch from a predominantly oxidative metabolism to glycolysis and the production of lactate even when oxygen is plentiful. This metabolic switch, known as the Warburg effect, was first described in the 1920s, and has fascinated and puzzled researchers ever since. However, a dramatic increase i...

Creatine Kinase (CK) catalyses the 'creatine shuttle', the reversible conversion of creatine phosphate to creatine with the liberation of ATP. This paper examines the potential role of the creatine shuttle in the provision of ATP during mouse preimplantation embryo development. Using quantitative PCR, transcripts of 4 subunit isoforms of CK - CKM,...

The oviduct plays a vital role in regulating the environment surrounding the gametes and early mammalian embryo. However, the permeability of the oviduct to circulating dietary-derived compounds remains relatively unknown. The present study has investigated the barrier properties of the oviduct epithelium in vitro to the movement of genistein, a so...

The widely accepted picture of embryo metabolism has originated from work carried out in a few specialised laboratories due to the technical difficulty of carrying out metabolite assays on small volume samples. We have refined the noninvasive enzymatic determination of spent embryo culture medium for use in a standard fluorescence plate reader. Usi...

Mammalian oocytes are rich in endogenous lipid, which provides a potential source of metabolic energy during oocyte maturation and early embryo development after fertilisation. Despite this, studies on early embryo metabolism have focussed on consumption of substrates from the culture medium, with comparatively little consideration for endogenous s...

Elevated plasma non-esterified fatty acid (NEFA) concentrations are associated with negative energy balance (NEB) and metabolic disorders such as obesity and type 2 diabetes. Increased plasma NEFA induce changes in the micro-environment of the ovarian follicle, which can compromise oocyte competence. Exposing oocytes to elevated NEFA concentrations...

Reduced oocyte and embryo quality are currently recognized as key factors in the problem of disappointing fertility in high producing dairy cows, but also in women undergoing assisted reproductive treatment. This review aims to highlight the importance of intrafollicular conditions in the subfertility problem, topical in both bovine and human resea...

There is evidence that expression and methylation of the imprinted paternally expressed gene 1/mesoderm-specific transcript homologue (PEG1/MEST) gene may be affected by assisted reproductive technologies (ARTs) and infertility. In this study, we sought to assess the imprinting status of the MEST gene in a large cohort of in vitro-derived human pre...

Reduced oocyte and embryo quality are recognised as major factors in the problem of disappointing fertility in high producing dairy cows. This review aims to shed more light on the importance of the intrafollicular environment in the subfertility problem in dairy cows. Metabolic disturbances associated with negative energy balance (NEB) early postp...

Growing evidence suggests that endogenous and exogenous fatty acids play diverse roles in developing mammalian oocytes and early embryos. In this review, we describe some of the regulatory roles of fatty acids in early development, in addition to their metabolic functions. We focus initially on the provision of individual fatty acids, and then disc...

In Vitro Embryo Production. (DOC)

mRNA Expression Analysis. (DOC)

Details of primers used for qRT-PCR. (DOCX)

Amino Acid Profiling. (DOC)

Elevated concentrations of serum non-esterified fatty acids (NEFA), associated with maternal disorders such as obesity and type II diabetes, alter the ovarian follicular micro-environment and have been associated with subfertility arising from reduced oocyte developmental competence. We have asked whether elevated NEFA concentrations during oocyte...

Insight into the normal and abnormal function of an interphase nucleus can be revealed by using fluorescence in situ hybridization (FISH) to determine chromosome copy number and/or the nuclear position of loci or chromosome territories. FISH has been used extensively in studies of mouse and human early embryos, however, translation of such methods...

Introduction The great challenge facing assisted conception is the need to reduce multiple birth rates whilst maintaining, or even improving, live birth rates. The availability of a defined, simple, robust bioassay of embryo viability is one way in which this might be achieved. In recent years, there has been intense research activity focused on sc...

In the recently published article “Amino acid metabolism of bovine blastocysts: A biomarker of sex and viability” by R. Sturmey et al. (Mol Reprod Dev, volume 77 (3): 285–296, 2010 [DOI: 10.1002/mrd.21145]), the Acknowledgment of grant support was inadvertently omitted. The omitted text is herein printed to address this error: RGS wishes to acknowl...

The ratio of male/female embryos may be modified by environmental factors such as maternal diet in vivo and the composition of embryo culture media in vitro. We have used amino acid profiling, a noninvasive marker of developmental potential to compare the effect of sex on the metabolism of bovine blastocysts conceived in vivo and in vitro. Blastocy...

In the recently published article "Amino acid metabolism of bovine blastocysts: A biomarker of sex and viability" by R. Sturmey et al. (Mol Reprod Dev, volume 77 (3): 285-296, 2010 [DOI: 10.1002/mrd.21145]), the Acknowledgment of grant support was inadvertently omitted.The omitted text is herein printed to address this error: RGS wishes to acknowle...

Sex-dependent differences in mammalian embryo phenotype are apparent at the preimplantation stage of development, before the appearance of sex-specific cells. The ratio of male:female embryos may be modified by environmental factors such as maternal diet in vivo and the composition of embryo culture media in vitro. We have used amino acid profiling...

Contents While much is known about the metabolism of exogenous nutrients such as glucose, lactate, pyruvate, amino acids by oocytes and pre‐implantation mammalian embryos, the role of endogenous stores, particularly lipid, has been largely overlooked. The presence of lipid within oocytes and early embryos has been long known, and comparisons betwee...

The oviduct (Fallopian tube) provides the environment for fertilisation and preimplantation development but little is known about the extent to which the supply of nutrients by the tube matches the nutritional requirements of the gametes and early embryo. Any consideration of these matters has to take into account the autonomy of the embryo, as ill...

Barrett's oesophagus (BO) carries an increased risk of progression to oesophageal adenocarcinoma. Chromoendoscopy with methylene blue (MB) can be used to facilitate identification of BO and target areas for biopsy. If photoexcited, MB can generate reactive oxygen species and genotoxic photodegradation products leading to DNA damage. We have previou...

This review examines the 'Quiet Embryo Hypothesis' which proposes that viable preimplantation embryos operate at metabolite or nutrient turnover rates distributed within lower ranges than those of their less viable counterparts. The 'quieter' metabolism consistent with this hypothesis is considered in terms of (i) 'functional' quietness; the contra...

Embryos with greater viability have a lower or 'quieter' amino acid metabolism than those which arrest. We have hypothesized this is due to non-viable embryos possessing greater cellular/molecular damage and consuming more nutrients, such as amino acids for repair processes. We have tested this proposition by measuring physical damage to DNA in bov...

This review assesses the ability of non-invasive 'amino acid profiling' to predict early embryo viability. The history of amino acid supplementation of embryo culture media and the role of amino acids in early embryo development are first considered and these are followed by a review of methods to quantify amino acid depletion and production by sin...

This review assesses the ability of non-invasive ‘amino acid profiling’ to predict early embryo viability. The history of amino acid supplementation of embryo culture media and the role of amino acids in early embryo development are first considered and these are followed by a review of methods to quantify amino acid depletion and production by sin...

The oviduct and uterus provide the environments for the earliest stages of mammalian embryo development. However, little is known about the mechanisms that underlie the formation of oviduct and uterine fluids, or the extent to which the supply of nutrients via these reproductive tract tissues matches the nutrient requirements of early embryos. Afte...

Glucose metabolism plays an important role in the preimplantation development of porcine embryos in vitro. As in mammalian species generally, a proportion of glucose consumed is converted to lactate by aerobic glycolysis generating small amounts of ATP, with the remainder oxidized by the TCA cycle. However, a striking feature of the porcine early e...

It has been proposed that preimplantation embryo viability during culture and following embryo transfer is associated with a 'quiet' metabolism. Viable embryos may be better equipped to contend with damage to the genome, transcriptome and proteome, or they may possess less damage than non-viable embryos. Much of the data for the quiet embryo hypoth...

The role of endogenous lipid in the provision of energy during in vitro maturation of immature porcine oocytes has been studied. Fluorescence resonance energy transfer (FRET) acceptor bleaching methods have been used to examine mitochondrial:lipid droplet co-localisation in live oocytes. FRET experiments demonstrate whether organelles are within th...

The pattern of depletion and appearance of a mixture of amino acids by single porcine blastocysts incubated in two different media has been determined non-invasively using high performance liquid chromatography. Zygotes were produced by the in vitro fertilisation of in vitro-matured, abattoir-derived immature oocytes and cultured in medium NCSU 23...

Pig oocytes and embryos differ from those of other species in having a large quantity of endogenous lipid, a potential role for which has yet to be identified. In the present study, the hypothesis that endogenous triglyceride acts as a metabolic substrate during in vitro maturation and early embryo development was tested. Embryos were produced by i...