Search Results

You are looking at 1 - 8 of 8 items for

  • Author: Kevin D Sinclair x
  • Refine by access: All content x
Clear All Modify Search
Kevin D Sinclair School of Biosciences, University of Nottingham, Loughborough, Leicestershire, UK

Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close
Open access
Kevin D Sinclair School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK

Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close
Open access
Ramiro Alberio School of Biosciences, University of Nottingham, Loughborough LE12 5RD, UK

Search for other papers by Ramiro Alberio in
Google Scholar
PubMed
Close
and
Kevin D Sinclair School of Biosciences, University of Nottingham, Loughborough LE12 5RD, UK

Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close
Free access
Chitra Joseph School of Biosciences and, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK

Search for other papers by Chitra Joseph in
Google Scholar
PubMed
Close
,
Morag G Hunter School of Biosciences and, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK

Search for other papers by Morag G Hunter in
Google Scholar
PubMed
Close
,
Kevin D Sinclair School of Biosciences and, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK

Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close
, and
Robert S Robinson School of Biosciences and, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK

Search for other papers by Robert S Robinson in
Google Scholar
PubMed
Close

The role of the tissue remodelling protein, secreted protein, acidic, cysteine-rich (SPARC), in key processes (e.g. cell reorganisation and angiogenesis) that occur during the follicle–luteal transition is unknown. Hence, we investigated the regulation of SPARC in luteinsing follicular cells and potential roles of SPARC peptide 2.3 in a physiologically relevant luteal angiogenesis culture system. SPARC protein was detected mainly in the theca layer of bovine pre-ovulatory follicles, but its expression was considerably greater in the corpus haemorrhagicum. Similarly, SPARC protein (western blotting) was up-regulated in luteinising granulosa but not in theca cells during a 6-day culture period. Potential regulatory candidates were investigated in luteinising granulosa cells: LH did not affect SPARC (P>0.05); transforming growth factor (TGF) B1 (P<0.001) dose dependently induced the precocious expression of SPARC and increased final levels: this effect was blocked (P<0.001) by SB505124 (TGFB receptor 1 inhibitor). Additionally, fibronectin, which is deposited during luteal development, increased SPARC (P<0.01). In luteal cells, fibroblast growth factor 2 decreased SPARC (P<0.001) during the first 5 days of culture, while vascular endothelial growth factor A increased its expression (P<0.001). Functionally, KGHK peptide, a SPARC proteolytic fragment, stimulated the formation of endothelial cell networks in a luteal cell culture system (P<0.05) and increased progesterone production (P<0.05). Collectively, these findings indicate that SPARC is intricately regulated by pro-angiogenic and other growth factors together with components of the extracellular matrix during the follicle–luteal transition. Thus, it is possible that SPARC plays an important modulatory role in regulating angiogenesis and progesterone production during luteal development.

Free access
Alexandra Thurston
Search for other papers by Alexandra Thurston in
Google Scholar
PubMed
Close
,
Jane Taylor Wolfson Centre for Stem Cells, Division of Gene Expression and Development, School of Biosciences, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG2 2RD, UK

Search for other papers by Jane Taylor in
Google Scholar
PubMed
Close
,
John Gardner Wolfson Centre for Stem Cells, Division of Gene Expression and Development, School of Biosciences, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG2 2RD, UK

Search for other papers by John Gardner in
Google Scholar
PubMed
Close
,
Kevin D Sinclair Wolfson Centre for Stem Cells, Division of Gene Expression and Development, School of Biosciences, Tissue Engineering and Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG2 2RD, UK

Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close
, and
Lorraine E Young
Search for other papers by Lorraine E Young in
Google Scholar
PubMed
Close

The preimplantation embryos of a range of mammals can be susceptible to disruptions in genomic imprinting mechanisms, resulting in loss of imprinting. Such disruptions can have developmental consequences involving foetal and placental growth such as Beckwith–Wiedemann syndrome in humans and large offspring syndrome in sheep. Our objective was to investigate the dynamics of establishing monoallelic expression of individual sheep imprinted genes post-fertilisation. Semi-quantitative RT-PCR was used to amplify cDNA from the sheep blastocyst, day 21 foetus and day 21 chorioallantois, to compare expression levels between biparental and parthenogenetic embryos in order to indicate allelic expression status. In common with other mammals, IGF2, PEG1 and PEG3 were paternally expressed in the day 21 conceptus, while H19, IGF2R, GRB10 and p57 KIP were maternally expressed. Interestingly, GNAS was maternally expressed in the foetus, but paternally expressed in the chorioallantois at day 21. Overall, the imprinting of ovine GRB10 and IGF2R was comparable with mouse but not with human. Contrary to the trophoblast-restricted maternal expression in both mouse and human, SASH2 (sheep homologue of Mash2/HASH2) was expressed in the ovine foetus and was biallelically expressed in the chorioallantois. Differential methylation of the H19 CTCF III upstream region and IGF2R DMR2 in the chorioallantois revealed predominantly paternal and maternal methylation respectively, indicating conservation of these imprinting regulatory regions. In blastocysts, IGF2R, GRB10 and SASH2 were expressed biallelically, while the other genes were not detected. Thus, for the majority of ovine imprinted genes examined, monoallelic expression does not occur until after the blastocyst stage.

Free access
Jaime Hughes Schools of Biosciences, Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK
Schools of Biosciences, Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK

Search for other papers by Jaime Hughes in
Google Scholar
PubMed
Close
,
Wing Yee Kwong Schools of Biosciences, Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK

Search for other papers by Wing Yee Kwong in
Google Scholar
PubMed
Close
,
Dongfang Li Schools of Biosciences, Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK

Search for other papers by Dongfang Li in
Google Scholar
PubMed
Close
,
Andrew M Salter Schools of Biosciences, Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK

Search for other papers by Andrew M Salter in
Google Scholar
PubMed
Close
,
Richard G Lea Schools of Biosciences, Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK

Search for other papers by Richard G Lea in
Google Scholar
PubMed
Close
, and
Kevin D Sinclair Schools of Biosciences, Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK

Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close

We previously reported increased follicular fluid progesterone (P4) concentrations in ewes fed an n-3 compared to an n-6 polyunsaturated fatty acid (PUFA)-enriched diet, but detected no differential effect of n-3 and n-6 PUFA-enriched high-density lipoproteins (HDL) on granulosa cell (GC) steroidogenesis in vitro. Moreover, net n-6 PUFA-enriched HDL reduced early embryo development, but in the absence of a net uptake of FA. Consequently, we hypothesised that a) effects of n-3 PUFA on ovarian steroidogenesis are mediated by theca rather than GCs and b) during embryo culture lipids are acquired solely from the albumin fraction of serum, so that albumin-delivered n-3 and n-6 PUFA exert a greater differential effect on embryo development than either low-density lipoprotein (LDL)- or HDL-delivered PUFA. Data confirmed that n-3 PUFA increases P4 production solely in theca cells and that this is associated with an increase in STAR transcript expression. Furthermore, LDL- and HDL-delivered n-3 PUFA are equally efficacious in this regard during the first 96 h of culture, but thereafter only HDL-delivered n-3 PUFA induces this effect in partially luteinised theca cells. We also demonstrate that albumin is the sole serum fraction that leads to a net uptake of FA during embryo culture. PUFA-enriched serum and albumin increased the yield of morphologically poorer quality blastocysts with increased transcript expression for the antioxidant enzyme SOD1. Important differential effects of n-3 and n-6 PUFA on ovarian steroidogenesis acting solely on theca cells are identified, but differential effects of PUFA on embryo development are less apparent.

Free access
Ali A Fouladi-Nashta
Search for other papers by Ali A Fouladi-Nashta in
Google Scholar
PubMed
Close
,
Karen E Wonnacott
Search for other papers by Karen E Wonnacott in
Google Scholar
PubMed
Close
,
Carlos G Gutierrez Division of Animal Sciences, Departamento de Reproducción, Roslin Institute, School of Biosciences, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK

Search for other papers by Carlos G Gutierrez in
Google Scholar
PubMed
Close
,
Jin G Gong Division of Animal Sciences, Departamento de Reproducción, Roslin Institute, School of Biosciences, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK

Search for other papers by Jin G Gong in
Google Scholar
PubMed
Close
,
Kevin D Sinclair
Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close
,
Philip C Garnsworthy
Search for other papers by Philip C Garnsworthy in
Google Scholar
PubMed
Close
, and
Robert Webb
Search for other papers by Robert Webb in
Google Scholar
PubMed
Close

Different fatty acid (FA) sources are known to influence reproductive hormones in cattle, yet there is little information on how dietary FAs affect oocyte quality. Effects of three dietary sources of FAs (supplying predominantly palmitic and oleic, linoleic (n-6) or linolenic (n-3) acids) on developmental potential of oocytes were studied in lactating dairy cows. A total of 12 Holstein cows received three diets containing rumen inert fat (RIF), soyabean or linseed as the main FA source for three periods of 25 days in a Latin-square design. Within each period, oocytes were collected in four ovum pick-up sessions at 3–4 day intervals. FA profiles in plasma and milk reflected profiles of dietary FA sources, but major FAs in granulosa cells were not affected. Dietary FA source did not affect plasma concentrations of leptin, insulin, IGF1, GH, or amino acids. RIF led to a higher proportion of cleaved embryos than soya or linseed, but blastocyst yield and embryo quality were not affected. It is concluded that the ovary buffers oocytes against the effects of fluctuations in plasma n-3 and n-6 FAs, resulting in only modest effects on their developmental potential.

Free access
Richard G Lea University of Nottingham, Sutton Bonington Campus, Loughborough, UK

Search for other papers by Richard G Lea in
Google Scholar
PubMed
Close
,
Beatrice Mandon-Pépin Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France

Search for other papers by Beatrice Mandon-Pépin in
Google Scholar
PubMed
Close
,
Benoit Loup Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France

Search for other papers by Benoit Loup in
Google Scholar
PubMed
Close
,
Elodie Poumerol Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France

Search for other papers by Elodie Poumerol in
Google Scholar
PubMed
Close
,
Luc Jouneau Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France

Search for other papers by Luc Jouneau in
Google Scholar
PubMed
Close
,
Biola F Egbowon University of Nottingham, Sutton Bonington Campus, Loughborough, UK

Search for other papers by Biola F Egbowon in
Google Scholar
PubMed
Close
,
Adelle Bowden University of Nottingham, Sutton Bonington Campus, Loughborough, UK

Search for other papers by Adelle Bowden in
Google Scholar
PubMed
Close
,
Corinne Cotinot Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France

Search for other papers by Corinne Cotinot in
Google Scholar
PubMed
Close
,
Laura Purdie University of Nottingham, Sutton Bonington Campus, Loughborough, UK

Search for other papers by Laura Purdie in
Google Scholar
PubMed
Close
,
Zulin Zhang James Hutton Institute, Craigebuckler, Aberdeen, UK

Search for other papers by Zulin Zhang in
Google Scholar
PubMed
Close
,
Paul A Fowler University of Aberdeen, Institute of Medical Sciences, Aberdeen, UK

Search for other papers by Paul A Fowler in
Google Scholar
PubMed
Close
, and
Kevin D Sinclair University of Nottingham, Sutton Bonington Campus, Loughborough, UK

Search for other papers by Kevin D Sinclair in
Google Scholar
PubMed
Close

Exposure of the fetal testis to numerous individual environmental chemicals (ECs) is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, ‘real-life’ exposure involves complex mixtures of ECs. Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at day 140. Fetal testes from day 140 pregnant ewes that were exposed transiently for 80-day periods during early (0–80 days), mid (30–110 days), or late (60–140 days) pregnancy had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance, and lowered testosterone; collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation are associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.

Open access