scholarly journals The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep

Reproduction ◽  
2010 ◽  
Vol 140 (5) ◽  
pp. 721-732 ◽  
Author(s):  
B K Campbell ◽  
N R Kendall ◽  
V Onions ◽  
R J Scaramuzzi
Keyword(s):  
Low Dose ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Insulin Response ◽  
Acute Effect ◽  
Arterial Infusion ◽  
Fourfold Increase ◽  
Glucose Challenge ◽  
Insulin Responses

Glucose is a critical metabolic fuel in most mammals although many foodstuffs also contain high levels of the monosaccharides, galactose and fructose. The aims of this work were to determine the insulin response to challenges of these sugars (experiment 1) and to examine the effect of systemic (experiment 2) and direct ovarian (experiment 3) infusion of these monosaccharides on ovarian function in ewes with autotransplanted ovaries. In experiment 1, both fructose (fourfold increase peaking in 2 h) and galactose (twofold increase; 30 min) elicited markedly different (P<0.001) insulin responses than glucose (sevenfold increase; 20 min) although the total amount released following fructose and glucose challenge was similar. In experiment 2, low-dose systemic fructose infusion had no acute effect on insulin but did depress FSH (P<0.05), and following the end of fructose infusion, a transient increase in FSH and insulin was observed (P<0.05), which was associated with an increase (P<0.05) in ovarian oestradiol and androstenedione secretion. Systemic infusion of neither glucose nor galactose had a significant effect on ovarian steroidogenesis although glucose acutely suppressed insulin levels. In contrast, ovarian arterial infusion of fructose and glucose had no effect on ovarian function whereas galactose suppressed ovarian follicle number and steroid secretion (P<0.05). In conclusion, this work indicates that fructose and galactose can influence ovarian functionin vivoin sheep and that different mechanisms are involved. Thus, fructose exerts stimulatory effects through indirect modulation of peripheral insulin and/or gonadotrophin levels whereas galactose exerts primarily suppressive effects by direct actions on the ovary.

Measurements of insulin responses as predictive markers of pancreatic β-cell mass in normal and β-cell-reduced lean and obese Göttingen minipigs in vivo

2006 ◽  
Vol 290 (4) ◽  
pp. E670-E677 ◽  
Author(s):  
Marianne O. Larsen ◽  
Bidda Rolin ◽  
Jeppe Sturis ◽  
Michael Wilken ◽  
Richard D. Carr ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Mass ◽  
Insulin Response ◽  
Study Groups ◽  
Β Cell ◽  
Intravenous Glucose ◽  
Body Weights ◽  
In Vivo Tests ◽  
Insulin Responses

At present, the best available estimators of β-cell mass in humans are those based on measurement of insulin levels or appearance rates in the circulation. In several animal models, these estimators have been validated against β-cell mass in lean animals. However, as many diabetic humans are obese, a correlation between in vivo tests and β-cell mass must be evaluated over a range of body weights to include different levels of insulin sensitivity. For this purpose, obese ( n = 10) and lean ( n = 25) Göttingen minipigs were studied. β-Cell mass had been reduced ( n = 16 lean, n = 5 obese) with a combination of nicotinamide (67 mg/kg) and streptozotocin (125 mg/kg), acute insulin response (AIR) to intravenous glucose and/or arginine was tested, pulsatile insulin secretion was evaluated by deconvolution ( n = 30), and β-cell mass was determined histologically. AIR to 0.3 ( r2= 0.4502, P < 0.0001) or 0.6 g/kg glucose ( r2= 0.6806, P < 0.0001), 67 mg/kg arginine ( r2= 0.5730, P < 0.001), and maximum insulin concentration ( r2= 0.7726, P < 0.0001) were all correlated to β-cell mass when evaluated across study groups, and regression lines were not different between lean and obese groups except for AIR to 0.3 g/kg glucose. Baseline pulse mass was not significantly correlated to β-cell mass across the study groups ( r2= 0.1036, NS), whereas entrained pulse mass did show a correlation across groups ( r2= 0.4049, P < 0.001). This study supports the use of in vivo tests of insulin responses to evaluate β-cell mass over a range of body weights in the minipig. Extensive stimulation of insulin secretion by a combination of glucose and arginine seems to give the best correlation to β-cell mass.

scholarly journals 279.Infertility in mice with null mutation of the Egr-1 transcription factor

2004 ◽  
Vol 16 (9) ◽  
pp. 279 ◽  
Author(s):  
D. L. Russell
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Prostaglandin E ◽  
Lh Receptor ◽  
Expression Of Genes

Female infertility has been reported in two lines of mice with mutation of the Egr-1 gene. One underlying cause of this defect is deficient LH production by pituitary gonadotropes. However, Egr-1 is also acutely regulated by both FSH and LH in ovarian granulosa cells (1). A role for this transcription factor in regulating gonadotrophin responsive target genes and ovarian function is hypothesised. Indeed the LH-receptor is a proposed target of Egr-1 regulation, but this has not been investigated in detail in vivo and is difficult to reconcile with the pattern of Egr-1 expression. In this study, the role of Egr-1 within the ovarian follicle was investigated using exogenous gonadotropin replacement in Egr-1–/– mice . Adult Egr-1–/– female mice superovulated by sequential PMSG and hCG stimulation and mated with proven male breeders failed to produced offspring while 90% of heterozygous females got pregnant and produced litters (7.4 � 2.9 pups per litter) within 22 days of stimulation. Recovery of oocytes from oviducts of immature superovulated mice revealed a reduced ovulation rate in null females (6.3 � 3.8 oocytes) compared to their heterozygous (18.0 � 6.5) and WT (17.8 � 6.8) littermates. Gross morphology and histology of exogenously stimulated ovaries were indistinguishable from their heterozygous or WT counterparts. Surprisingly, no alteration was detectable in the mRNA expression of previously reported direct Egr-1 responsive genes, namely LH-receptor and membrane prostaglandin E synthase (mPGES). Nor were mRNA for two critical ovulatory genes with putative Egr-1 response elements, ADAMTS-1 or versican V1 altered. Temporal and spatial expression of genes involved in ovarian steroidogenesis, P450scc and Cyp17 and LH-receptor, were indistinguishable from normal littermates during exogenously controled follicular development. Combined observations of acute Egr-1 induction by gonadotropins, reduced ovulation and complete infertility suggest an important role for Egr-1 in ovarian function. However, genes identified as targets of Egr-1 regulation in other studies proved to be Egr-1 independent in this model. (1) Russell et al. (2003) Mol. Endo. 17, 520.

scholarly journals Toluene Can Disrupt Rat Ovarian Follicullogenesis and Steroidogenesis and Induce Both Autophagy and Apoptosis

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1153
Author(s):  
Abdulkarem Alrezaki ◽  
Nouf Aldawood ◽  
Lamjed Mansour ◽  
Mukhtar Ahmed ◽  
Alexander V. Sirotkin ◽  
...  
Keyword(s):  
Low Dose ◽  
Ovarian Function ◽  
Ovarian Cells ◽  
Cell Proliferation And Differentiation ◽  
Female Wistar Rats ◽  
Toluene Exposure ◽  
Ovarian Structure ◽  
Encoding Gene ◽  
High Doses

Toluene has been shown to be highly toxic to humans and animals and can cause damage to various tissues. However, studies reporting its effects on ovarian function are still limited. In this study, we investigated the in vivo effect of toluene using female Wistar rats. We found that toluene exposure decreased ovarian weight and affected ovarian structure by increasing the number of abnormally growing follicles. Moreover, it significantly increased progesterone and testosterone levels. We also showed that toluene exposure decreased GDF-9 protein and its encoding gene. In addition, it inhibited the expression of most of the genes involved in granulosa cell proliferation and differentiation, such as Insl3, ccnd2 and actb. The TUNEL assay showed that apoptosis occurred at the middle and high doses only (4000 and 8000 ppm, respectively), whereas no effect was observed at the low dose (2000 ppm). Interestingly, we showed that toluene exposure induced autophagy as LC3 protein and its encoding gene significantly increased for all doses of treatment. These results may suggest that the activation of autophagy at a low dose of exposure was to protect ovarian cells against death by inhibiting apoptosis, whereas its activation at high doses of exposure triggered apoptosis leading to cell death.

228. In vivo evidence for a role of bone morphogenetic protein-4 in ovarian function

2005 ◽  
Vol 17 (9) ◽  
pp. 89
Author(s):  
P. S. Tanwar ◽  
J. R. McFarlane
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Passive Immunization ◽  
Control Group ◽  
Bone Morphogenetic Protein 4 ◽  
Primordial Follicles ◽  
Morphogenetic Protein

Bone morphogenetic proteins (BMPs) were first identified on the basis of their bone inducing capacity, and later shown to be members of the transforming growth factor β (TGF β) super family. Nilsson et al.1 studied the effect of BMP-4 on follicular development in rat ovaries and found that the addition of BMP-4 to whole ovary cultures led to more numbers of developing primary follicles but less numbers of primordial follicles. Their studies indicate that BMP-4 acts as a transition factor for the conversion of primordial follicles to primary follicles. To test this hypothesis in-vivo, we conducted passive immunization studies against BMP-4 in prepubertal female mice. The mice were divided in to four groups (n = 5), and given daily SC injections of the following treatment: anti BMP-4 (50μg), PMSG (10 IU) (pregnant mare serum gonadotropin) with and without anti BMP-4 (0.5 mg/mL) and PBS for 3 days. All experimentation was approved by animal ethics committee, University of New England, Armidale, NSW. On the fourth day the mice were killed and the ovaries removed and weighed. The mice treated with anti BMP-4 had significantly smaller ovaries (4.1 ± 0.4 mg) than the control group (8.6 ± 0.9 mg). PMSG stimulated ovarian weight (21.0 ± 1.2 mg) but anti BMP-4 (23.2 ± 1.3 mg) did not significantly affect the weight of the stimulated ovaries. This data confirms BMP-4 is important in ovarian function; however, it is unclear whether this effect is on the ovary directly or via FSH. (1)Nilsson, E. E., Skinner, M.K. (2003). Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biology of Reproduction 69, 1265–1272.

scholarly journals The effect of a direct arterial infusion of insulin and glucose on the ovarian secretion rates of androstenedione and oestradiol in ewes with an autotransplanted ovary

1999 ◽  
Vol 163 (3) ◽  
pp. 531-541 ◽  
Author(s):  
JA Downing ◽  
J Joss ◽  
RJ Scaramuzzi
Keyword(s):  
Ovarian Function ◽  
Ovarian Follicle ◽  
Plasma Concentrations ◽  
Ovulation Rate ◽  
Follicle Development ◽  
Short Term ◽  
Arterial Infusion ◽  
Follicle Selection ◽  
Metabolic Hormone ◽  
Secretion Rates

Improving ewe nutrition even for short periods will increase ovulation rate. The increased nutrients must in some way affect the number of follicles that develop to the pre-ovulatory stage. One possible mechanism is that a nutrient or a metabolic hormone that responds to nutrition might act directly on the ovary to influence follicle development and/or follicle selection. In the study described here, insulin and glucose, alone or together, were infused directly into the ovarian artery of ewes with an autotransplanted ovary, for 13.5 h on day 11 of the oestrous cycle. The pattern of androstenedione and oestradiol secretion in response to a GnRH-stimulated LH pulse was measured 2.5 h before and 12.5 h and 24.5 h after the start of the infusion. Glucose or insulin infused alone had no effect on the secretion of androstenedione and oestradiol. However, when infused together, they decreased significantly the secretion of androstenedione and, to a lesser extent, oestradiol. We suggest that the sudden availability of additional glucose and insulin increases insulin-stimulated glucose uptake by the follicle. This leads to an inhibition of LH-stimulated steroidogenesis by the ovarian follicle which occurs in the absence of any detectable changes in circulating plasma concentrations of FSH. These results show that insulin and glucose act together to influence ovarian function directly and suggest that the effects of short-term nutrition on ovulation rate may be mediated by a direct ovarian action of insulin and glucose.

scholarly journals Noninvasive assessment of pancreatic β-cell function in vivo with manganese-enhanced magnetic resonance imaging

2009 ◽  
Vol 296 (3) ◽  
pp. E573-E578 ◽  
Author(s):  
Patrick F. Antkowiak ◽  
Sarah A. Tersey ◽  
Jeffrey D. Carter ◽  
Moriel H. Vandsburger ◽  
Jerry L. Nadler ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Low Dose ◽  
Cell Function ◽  
Diabetic Mice ◽  
Resonance Imaging ◽  
Β Cell ◽  
Glucose Challenge ◽  
Β Cell Function

Loss of β-cell function in type 1 and type 2 diabetes leads to metabolic dysregulation and inability to maintain normoglycemia. Noninvasive imaging of β-cell function in vivo would therefore provide a valuable diagnostic and research tool for quantifying progression to diabetes and response to therapeutic intervention. Because manganese (Mn2+) is a longitudinal relaxation time (T1)-shortening magnetic resonance imaging (MRI) contrast agent that enters cells such as pancreatic β-cells through voltage-gated calcium channels, we hypothesized that Mn2+-enhanced MRI of the pancreas after glucose infusion would allow for noninvasive detection of β-cell function in vivo. To test this hypothesis, we administered glucose and saline challenges intravenously to normal mice and mice given high or low doses of streptozotocin (STZ) to induce diabetes. Serial inversion recovery MRI was subsequently performed after Mn2+ injection to probe Mn2+ accumulation in the pancreas. Time-intensity curves of the pancreas (normalized to the liver) fit to a sigmoid function showed a 51% increase in signal plateau height after glucose stimulation relative to saline ( P < 0.01) in normal mice. In diabetic mice given a high dose of STZ, only a 9% increase in plateau signal intensity was observed after glucose challenge ( P = not significant); in mice given a low dose of STZ, a 20% increase in plateau signal intensity was seen after glucose challenge ( P = 0.02). Consistent with these imaging findings, the pancreatic insulin content of high- and low-dose STZ diabetic mice was reduced about 20-fold and 10-fold, respectively, compared with normal mice. We conclude that Mn2+-enhanced MRI demonstrates excellent potential as a means for noninvasively monitoring β-cell function in vivo and may have the sensitivity to detect progressive decreases in function that occur in the diabetic disease process.

Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice

2000 ◽  
Vol 279 (5) ◽  
pp. E956-E962 ◽  
Author(s):  
Kristin Persson ◽  
Ronald L. Gingerich ◽  
Sonali Nayak ◽  
Keiji Wada ◽  
Etsuko Wada ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Response ◽  
Biologically Active ◽  
Simultaneous Increase ◽  
Glucose Challenge ◽  
Elisa Technique ◽  
Genetic Targeting ◽  
Grp Receptors ◽  
Insulin Responses ◽  
Grp Receptor

By applying a newly developed ELISA technique for determining biologically active intact glucagon-like peptide [GLP-1, GLP-1-(7–36)amide] in mouse, plasma baseline GLP-1 in normal NMRI mice was found to be normally distributed (4.5 ± 0.3 pmol/l; n = 72). In anesthetized mice, gastric glucose (50 or 150 mg) increased plasma GLP-1 levels two- to threefold ( P < 0.01). The simultaneous increase in plasma insulin correlated to the 10-min GLP-1 levels ( r = 0.36, P < 0.001; n = 12). C57BL/6J mice deleted of the gastrin-releasing peptide (GRP) receptor by genetic targeting had impaired glucose tolerance ( P = 0.030) and reduced early (10 min) insulin response ( P = 0.044) to gastric glucose compared with wild-type controls. Also, the GLP-1 response to gastric glucose was significantly lower in the GRP receptor-deleted mice than in the controls ( P = 0.045). In conclusion, this study has shown that 1) plasma levels of intact GLP-1 increase dose dependently on gastric glucose challenge in correlation with increased insulin levels in mice, and 2) intact GRP receptors are required for normal GLP-1 and insulin responses and glucose tolerance after gastric glucose in mice.

scholarly journals Gap-junctional communication in mouse cumulus-oocyte complexes: implications for the mechanism of meiotic maturation

Reproduction ◽  
2002 ◽  
pp. 41-52 ◽  
Author(s):  
RJ Webb ◽  
H Bains ◽  
C Cruttwell ◽  
J Carroll
Keyword(s):  
Ovarian Function ◽  
Ovarian Follicle ◽  
Somatic Cells ◽  
Cumulus Cells ◽  
Meiotic Maturation ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Gap Junctional

The mechanisms underlying the hormonal stimulation of meiotic maturation are not understood. The most prevalent hypothesis is that hormone-induced maturation is stimulated by an increase in the intracellular messengers, cAMP or Ca2+. This study investigated whether Ca2+ transients in somatic cells can lead to Ca2+ transients in the oocyte, and whether hormones that stimulate meiotic maturation of mouse oocytes in vitro and in vivo stimulate an increase in intracellular Ca2+. Of a range of potential agonists of Ca2+ release, ATP and UTP were the only agents that stimulated Ca2+ release in cumulus cells. ATP-induced Ca2+ release is from intracellular stores, as the response is not blocked by chelation of extracellular Ca2+, but is inhibited by the Ca2+-ATPase inhibitor, thapsigargin. ATP and UTP are equipotent, consistent with the receptor being of the P2Y2 type. Confocal microscopy was used to show that ATP-induced Ca2+ release in cumulus cells leads to a Ca2+ increase in the oocyte. Inhibition of gap-junctional communication using carbenoxolone, as assayed by dye transfer, inhibited the diffusion of the Ca2+ signal from the cumulus cells to the oocyte. Thus, provided that a Ca2+ signal is generated in the somatic cells in response to maturation-inducing hormones, it is feasible that a Ca2+ transient is generated in the oocyte. However, FSH and EGF, both of which stimulate maturation in vitro, have no effect on Ca2+ in cumulus--oocyte complexes. Furthermore, LH, which leads to meiotic maturation in vivo, did not stimulate Ca2+ release in acutely isolated granulosa cells from preovulatory mouse follicles. These studies indicate that ATP may play a role in modulating ovarian function and that diffusion of Ca2+ signals through gap junctions may provide a means of communication between the somatic and germ cells of the ovarian follicle. However, our data are not consistent with a role for Ca2+-mediated communication in hormone-mediated induction of meiosis in mice.

scholarly journals Ovarian follicle development in Booroola sheep exhibiting impaired bone morphogenetic protein signalling pathway

Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 689-696 ◽  
Author(s):  
Chantelle Ruoss ◽  
Amanda Tadros ◽  
Tim O'Shea ◽  
Jim McFarlane ◽  
Ghanim Almahbobi
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Primordial Follicle ◽  
Signalling Pathway ◽  
Primordial Follicles ◽  
Merino Sheep ◽  
Ovarian Follicle Development ◽  
Morphogenetic Protein

The role of bone morphogenetic proteins (BMPs) in the regulation of ovarian function has been extensively investigated but the mechanism of regulation is not well understood. The aim of this study was to investigate the effect of mutation in the BMP receptor in Booroola sheep on the number of primordial follicles and rate of follicle recruitment in comparison with that in normal merino sheep in vivo. Whole sheep ovaries at the time of birth, 1.5 and 5 years old were collected and processed for the follicle quantification, using computerised stereological methods and statistical analyses. At birth, the total number of primordial follicles in Booroola sheep was significantly lower than in merino sheep. At 1.5 and 5 years, a reversed pattern in favour of Booroola ewes was seen with significantly more primordial follicles than merino. In parallel, the rate of primordial follicle recruitment to developing cohort was substantially lower in Booroola ewes with only 51 and 66% of primordial follicle consumption at 1.5 and 5 years respectively compared to 92 and 97% in merino ewes. On other hand, the mean numbers of developing primary follicles were smaller in Booroola sheep at the time of birth, yet, Booroola ewes possess more primary follicles than merino at 1.5 years. These findings suggest that attenuation of the intraovarian signalling pathway of BMPs may in fact be a successful means of rationalising follicle consumption, preventing unnecessary loss of follicles from the initial primordial follicle pool, hence increasing reproductive longevity and fertility.

Functional and Immunohistochemical Evaluation of Porcine Neonatal Islet-Like Cell Clusters

2003 ◽  
Vol 12 (1) ◽  
pp. 13-25 ◽  
Author(s):  
T. B. Nielsen ◽  
K. B. Yderstraede ◽  
H. D. Schrøder ◽  
Jens Juul Holst ◽  
Klaus Brusgaard ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Nude Mice ◽  
Cell Mass ◽  
Diabetic Patients ◽  
Type I ◽  
Fourfold Increase ◽  
Cell Clusters ◽  
Glucose Challenge

Porcine neonatal islet-like cell clusters (NICCs) may be an attractive source of insulin-producing tissue for xenotransplantation in type I diabetic patients. We examined the functional and immunohistochemical outcome of the islet grafts in vitro during long-term culture and in vivo after transplantation to athymic nude mice. On average we obtained 29,000 NICCs from each pancreas. In a perifusion system, NICCs responded poorly to a glucose challenge alone, but 10 mmol/L arginine elicited a fourfold increase in insulin secretion and 16.7 mmol/L glucose + 10 mmol/L arginine caused a sevenfold increase in insulin secretion, indicating some sensitivity towards glucose. Hormone content as well as the number of hormone-containing cells increased for the first 14 days of culture. When NICCs were stained for hormones, proliferation (Ki67), and duct cells (CK7), some insulin- and glucagon-positive cells co-stained for proliferation. However no co-staining was observed between insulin- and glucagon-positive cells or between hormone- and CK7-positive cells. Following transplantation of 2000 NICCs under the renal capsule of diabetic nude mice, BG levels were normalized within an average of 13 weeks. Oral and IP glucose tolerance tests revealed a normal or even faster clearance of a glucose load compared with normal controls. Immunohistochemical examination of the grafts revealed primarily insulin-positive cells. In summary, in vitro, NICCs responded to a challenge including glucose and arginine. There was a potential for expansion of the β-cell mass of NICCs in vitro as well as in vivo where NICCs eventually may normalize blood glucose of diabetic mice.

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