scholarly journals Chronic Undernutrition Inhibits KNDy Neurons in Ovariectomized Ewe Lambs

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A534-A534
Author(s):  
KaLynn Harlow ◽  
Max Griesgraber ◽  
Andrew Seman ◽  
Sydney Shuping ◽  
Jeffrey Sommer ◽  
...  

Abstract Undernutrition negatively impacts reproductive success, at least in part, through a central suppression of GnRH secretion. Given that GnRH neurons are devoid of receptors for peripheral metabolic hormones such as leptin and insulin, nutritional regulation of GnRH secretion must be through afferent input. Neurons which co-express kisspeptin, neurokinin B (NKB), and dynorphin, termed KNDy neurons, are a unique population of cells in the arcuate nucleus (ARC) of the hypothalamus and are believed to play a critical role in GnRH/LH pulse generation. With our recent evidence that chronic feed restriction reduced kisspeptin and NKB in young, castrated male sheep, we hypothesized that nutrient restriction would inhibit expression of the KNDy neuron peptides kisspeptin and NKB, while increasing dynorphin expression in young, ovariectomized female sheep. Fifteen ewe lambs were ovariectomized and were fed to maintain body weight (n=7; Fed) or feed-restricted to lose 20% of pre-study body weight (FR; n=8). Blood samples were taken weekly every 12 minutes for 4.5 hours via jugular venipuncture and plasma was stored at -20°C until assessment of LH using radioimmunoassay. Body weights were recorded weekly and feed amounts were adjusted to achieve desired body weights. Following blood collection at Week 13, animals were euthanized, brain tissue was perfused with 4% paraformaldehyde, and tissue containing the hypothalamus was collected for assessment of KNDy neuropeptide mRNA abundance by in situ hybridization (RNAscope). At Week 13, the average percent change in body weight was clearly evident (Fed, 7.35 +/- 2.2% vs FR, -21.36 +/- 0.9%), and mean LH concentrations were lower in FR ewes (10.70 +/- 3.1 ng/ml) compared to Fed controls (20.98 +/- 3.8 ng/ml). Data analyzed to date for kisspeptin, NKB, and dynorphin in the ARC show that feed restriction reduced the number of kisspeptin mRNA-expressing cells (Fed, 165 +/- 25 vs FR, 9.25 +/- 6), the number of NKB mRNA-expressing cells (Fed, 141 +/- 28 vs FR, 24 +/- 5), and the number of dynorphin mRNA-expressing cells (Fed, 109 +/- 41 vs FR, 29.5 +/- 24). Together, these findings demonstrate that chronic feed restriction suppresses KNDy neurons and supports a role for these key reproductive neurons in the central mechanism governing GnRH/LH secretion during undernutrition in female sheep.

1979 ◽  
Vol 28 (3) ◽  
pp. 297-307 ◽  
Author(s):  
J. F. Quirke

ABSTRACTGroups of spring-born Galway (G) and Fingalway (F) ewe lambs were fed a concentrate diet either ad libitum (H) or at a restricted level (L) during the period 25 July to 16 October 1974 in order to induce differences in body weight at the start of the breeding season. The mean live weights of the GL, GH, FL and FH groups on 16 October 1974 were 37·8 ± 1·3, 44·6 ± 1·3, 35·1 ± 1·1 and 41·9 ± 1·2 kg respectively. More than 95% of the lambs in all four groups attained puberty before 28 February 1975. Galway ewe lambs reached puberty later in the breeding season and were older and heavier at puberty than Fingalways. Animals fed ad libitum were heavier at puberty and attained puberty earlier in the season and at a younger age than those on the restricted feeding regime.Both conception rate and litter size were lower in Galways than Fingalways. There was no evidence of any effect of the nutritional treatments on conception rate or litter size. The mean body weights at puberty for ewes which lambed and those which were barren were 41·9 ± 0·49 and 41·5 ± 0·78 kg respectively. The birth weight and growth rate of the progeny of the ewe lambs was similar for the two breeds and was not influenced by the previous nutritional treatment of the dams. The total lamb mortality between birth and weaning was 40·3%, and 72% of all deaths occurred within 48 h of birth. Losses among twins (48%) were particularly heavy.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sydney L Shuping ◽  
Allison N Renwick ◽  
Lynn Harlow ◽  
Jeffrey R Sommer ◽  
Christina M Merkley ◽  
...  

Abstract Proper energy balance is important to ensure reproductive success. Chronic nutrient restriction is known to suppress hypothalamic-pituitary function, but the central mechanisms whereby undernutrition inhibits GnRH/LH secretion remain largely unknown. KNDy neurons, which co-express kisspeptin, neurokinin B (NKB), and dynorphin, form a unique population of cells in the arcuate nucleus (ARC) of the hypothalamus and play a critical role in GnRH/LH pulse generation. Based on recent evidence from our lab that chronic feed restriction reduces kisspeptin and NKB protein expression in young male sheep, we hypothesized that nutrient restriction would inhibit mRNA abundance for kisspeptin and NKB in the same animals. Fourteen wethers were placed into a fed to maintain body weight group (n=6; Fed) or a feed-restricted to lose 15-20% of pre-study body weight group (FR; n=8). Weekly blood samples (every 12 minutes for 4.5 hours) were taken via jugular venipuncture and plasma was stored at -20°C until the time of radioimmunoassay. Weekly body weights were recorded and feed amounts were adjusted to achieve desired body weights. At Week 13, animals were euthanized following blood collection, brain tissue was perfused with 4% paraformaldehyde, and tissue containing the hypothalamus was collected. Following submersion in 20% sucrose for at least four weeks, hypothalamic blocks were sectioned at 50 µm on a freezing microtome, and stored in a cryopreservative solution until processing. At Week 13, the average percent change in body weight was clearly evident (Fed, 6.79 + 3.4% vs FR, -19.82 ± 1.6%), and mean LH was significantly lower in FR wethers (13.41 + 3.7 ng/ml) compared to Fed controls (26.43 + 2.5 ng/ml). To assess changes in mRNA abundance, we used a relatively new in situ hybridization technique, RNAscope, to quantify mRNA for kisspeptin and NKB in the ARC with probes that were ovine-specific. Results showed that feed restriction reduced the number of kisspeptin mRNA-expressing cells (Fed, 231.2 + 14.4 vs FR, 100.3 + 35.9) and NKB mRNA-expressing cells (Fed, 192.7 + 18.4 vs FR, 97.3 + 21.7) per hemi-section. Furthermore, analysis of kisspeptin and NKB co-expressing cells (30 cells/animal) revealed that feed restriction significantly reduced the average mRNA integrated density for NKB, but not kisspeptin, compared to Fed controls. Together, these findings further support a role for kisspeptin and NKB in the central mechanism governing GnRH/LH secretion during undernutrition in male sheep.


Reproduction ◽  
2018 ◽  
Vol 156 (3) ◽  
pp. R83-R99 ◽  
Author(s):  
Casey C Nestor ◽  
Michelle N Bedenbaugh ◽  
Stanley M Hileman ◽  
Lique M Coolen ◽  
Michael N Lehman ◽  
...  

Early work in ewes provided a wealth of information on the physiological regulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion by internal and external inputs. Identification of the neural systems involved, however, was limited by the lack of information on neural mechanisms underlying generation of GnRH pulses. Over the last decade, considerable evidence supported the hypothesis that a group of neurons in the arcuate nucleus that contain kisspeptin, neurokinin B and dynorphin (KNDy neurons) are responsible for synchronizing secretion of GnRH during each pulse in ewes. In this review, we describe our current understanding of the neural systems mediating the actions of ovarian steroids and three external inputs on GnRH pulsatility in light of the hypothesis that KNDy neurons play a key role in GnRH pulse generation. In breeding season adults, estradiol (E2) and progesterone decrease GnRH pulse amplitude and frequency, respectively, by actions on KNDy neurons, with E2decreasing kisspeptin and progesterone increasing dynorphin release onto GnRH neurons. In pre-pubertal lambs, E2inhibits GnRH pulse frequency by decreasing kisspeptin and increasing dynorphin release, actions that wane as the lamb matures to allow increased pulsatile GnRH secretion at puberty. Less is known about mediators of undernutrition and stress, although some evidence implicates kisspeptin and dynorphin, respectively, in the inhibition of GnRH pulse frequency by these factors. During the anoestrus, inhibitory photoperiod acting via melatonin activates A15 dopaminergic neurons that innervate KNDy neurons; E2increases dopamine release from these neurons to inhibit KNDy neurons and suppress the frequency of kisspeptin and GnRH release.


Endocrinology ◽  
2018 ◽  
Vol 159 (9) ◽  
pp. 3187-3199 ◽  
Author(s):  
Peyton W Weems ◽  
Lique M Coolen ◽  
Stanley M Hileman ◽  
Steven Hardy ◽  
Rick B McCosh ◽  
...  

Abstract A subpopulation of neurons located within the arcuate nucleus, colocalizing kisspeptin, neurokinin B, and dynorphin (Dyn; termed KNDy neurons), represents key mediators of pulsatile GnRH secretion. The KNDy model of GnRH pulse generation proposes that Dyn terminates each pulse. However, it is unknown where and when during a pulse that Dyn is released to inhibit GnRH secretion. Dyn acts via the κ opioid receptor (KOR), and KOR is present in KNDy and GnRH neurons in sheep. KOR, similar to other G protein–coupled receptors, are internalized after exposure to ligand, and thus internalization can be used as a marker of endogenous Dyn release. Thus, we hypothesized that KOR will be internalized at pulse termination in both KNDy and GnRH neurons. To test this hypothesis, GnRH pulses were induced in gonad-intact anestrous ewes by injection of neurokinin B (NKB) into the third ventricle and animals were euthanized at times of either pulse onset or termination. NKB injections produced increased internalization of KOR within KNDy neurons during both pulse onset and termination. In contrast, KOR internalization into GnRH neurons was seen only during pulse termination, and only in GnRH neurons within the mediobasal hypothalamus (MBH). Overall, our results indicate that Dyn is released onto KNDy cells at the time of pulse onset, and continues to be released during the duration of the pulse. In contrast, Dyn is released onto MBH GnRH neurons only at pulse termination and thus actions of Dyn upon KNDy and GnRH cell bodies may be critical for pulse termination.


1955 ◽  
Vol 6 (2) ◽  
pp. 343 ◽  
Author(s):  
GC Taneja

The growth rates between 5 and 11 months, and 11 and 17 months, of 284 ewe lambs born in the spring of 19.51, and 269 born in the autumn of 1952, were analysed. The growth rates were calculated as the differences between the logarithms of the successive body weights. The analysis of the data indicated that: (i) there is a negative correlation between the two growth rates due to environment in the two different periods; (ii) the genetic correlation between the two growth rates is zero, and it therefore appears that there are different sets of growth genes operating during the two periods of growth; (iii) the heritability for the first and second periods of growth is 0.27 and 0.31 in one group and 0.04 and 0.22 in the other group respectively. Environment therefore plays a greater part in causing variation in the growth rates than does heredity.


1995 ◽  
Vol 60 (2) ◽  
pp. 185-195 ◽  
Author(s):  
S. L. Fossceco ◽  
D. R. Notter

AbstractHeritabilities (h2) and genetic correlations (rc) involving body weights, measures of testes size and ewe lamb reproduction were calculated using 953 spring-born lambs produced during formation of a three-breed composite population containing 0·50 Dorset, 0·25 Rambouillet and 0·25 Finnish Landrace breeding. The h2 of body weight ranged from 0·2 to 0·3 between 45 and 150 days of age, but increased to 0·41 at the start of breeding of ewe lambs at about 6 months of age. Additive maternal effects were not important, perhaps because intensive housing encouraged cross-suckling. Testes size was measured as scrotal circumference (SC), SC with linear adjustment for weight (SCW) and SC divided by the one-third power of body weight (RSC). The h2 of SC traits was highest at 90 days (0·52 for SC, 0·62 for RSC and 0·57 for SCW), and h2 for age at maximum SC growth rate (i.e. TI, the inflexion point of a logistic SC growth curve) was 0·49. The h2 of ewe lamb fertility in autumn was 0·09 but the h2 for frequency of remating the following spring was 0·41. The h2 for ewe lamb litter size in these data was zero. At 90 days, rc between alternative measures of testes size exceeded 0·86; rG with body weight were 0·67 for SC, 0·53 for RSC and –0·74 for TI. The rG with ewe lamb fertility for 90-day weight, SC, RSC and SCW and for TI were –0·25, 0·20, 0·25, 0·38 and –0·32, respectively. The rc for these traits with spring remating were 0·34, 0·34, 0·26, 0·10 and –0·48, respectively.


1959 ◽  
Vol 10 (3) ◽  
pp. 387 ◽  
Author(s):  
F Cockrem ◽  
AL Rae

A study has been made of the pleiotropic effects of the gene N on the body growth and the carcass of the Sew Zealand Romney lamb. Measurements of body weight and height at withers were taken from birth to about 5 months of age for lambs born in 1952 and 1953 from matings of N/+ x +/+, N/N x N/N, N/N x N/+, and N/+ x N/+ parents. In 1952, +/+ lambs grew faster than N/+ or N/N lambs and this was shown in the greater body weight of the +/+ lambs at 30 days of age. The differences in weight gains corrected for initial weight were greater for single lambs than for twin lambs. The differences in the height at withers were proportional to those in body weight except for the N/N lambs. The N/N lambs had a greater height at withers for their body weight but this could have been the result of factors other than the gene N which were associated with the N–type flock. N–type ewe lambs kept up to 18 months of age maintained lower body weights than +/+ lambs. In 1953 no differences between N/+ and +/+ lambs were found in body growth. It is suggested that a genetic-environment interaction exists for body growth and that the environmental factor is possibly one of climate. No differences were found between the carcass measurements of N/+ and +/+ ram lambs which could not be attributed to the previous differences in body growth.


1995 ◽  
Vol 147 (2) ◽  
pp. 217-223
Author(s):  
L G Moore ◽  
K P McNatty ◽  
K L Isaacs ◽  
S Lun ◽  
W Ng Chie ◽  
...  

Abstract The aim of this study was to examine the effect of the FecBB fecundity gene on plasma concentrations and pituitary content of growth hormone (GH) in sheep. No differences were found between homozygous carriers (BB) and non carriers (++) of the FecBB gene with regard to pituitary GH contents in both ovariectomized and intact ewes. However, ovariectomized ewes had higher levels of pituitary GH than intact ewes (P<0·01). There were no differences between FecBB genotypes with respect to plasma concentrations of GH in 6-year-old ovariectomized ewes bled every 10 min for 12 h or in ram lambs bled weekly during their first year of life. GH levels in the rams decreased until week 27, increased to a peak at week 31 then decreased before increasing again at week 43. Mean plasma GH concentrations in the ewe lambs bled weekly for a year decreased until week 19 then remained at approximately this level for the remainder of the year. Mean GH plasma concentrations in the ram lambs were higher than in the ewe lambs (P<0·001). Ewe lambs that were homozygous for the FecBB gene had lower body weights (P<0·05) and had higher levels of GH (P<0·01) than non carrier ewe lambs during their first year. Before the average age of first behavioural oestrus (36 weeks) GH levels in the ewe lambs were negatively correlated with body weights (r=−0·69, P<0·001, n=22). When body weight was included as a covariate in analysis of variance the genotype difference in ewe lamb plasma GH concentrations was no longer significant. In summary, pituitaries from ovariectomized ewes had higher levels of GH than those from intact ewes. There were no FecBB gene specific differences in pituitary levels of GH, the profile of plasma GH in 6-year-old ovariectomized ewes or in ram lambs during their first year of life. BB ewe lambs had higher levels of GH than ++ ewe lambs during their first year; however, this difference was probably due to the BB ewes having lower body weights than the ++ ewes because body weight was negatively correlated with mean GH levels. Journal of Endocrinology (1995) 147, 217–223


2014 ◽  
Vol 84 (1-2) ◽  
pp. 5-11 ◽  
Author(s):  
Eun Y. Jung ◽  
Sung C. Jun ◽  
Un J. Chang ◽  
Hyung J. Suh

Previously, we have found that the addition of L-ascorbic acid to chitosan enhanced the reduction in body weight gain in guinea pigs fed a high-fat diet. We hypothesized that the addition of L-ascorbic acid to chitosan would accelerate the reduction of body weight in humans, similar to the animal model. Overweight subjects administered chitosan with or without L-ascorbic acid for 8 weeks, were assigned to three groups: Control group (N = 26, placebo, vehicle only), Chito group (N = 27, 3 g/day chitosan), and Chito-vita group (N = 27, 3 g/day chitosan plus 2 g/day L-ascorbic acid). The body weights and body mass index (BMI) of the Chito and Chito-vita groups decreased significantly (p < 0.05) compared to the Control group. The BMI of the Chito-vita group decreased significantly compared to the Chito group (Chito: -1.0 kg/m2 vs. Chito-vita: -1.6 kg/m2, p < 0.05). The results showed that the chitosan enhanced reduction of body weight and BMI was accentuated by the addition of L-ascorbic acid. The fat mass, percentage body fat, body circumference, and skinfold thickness in the Chito and Chito-vita groups decreased more than the Control group; however, these parameters were not significantly different between the three groups. Chitosan combined with L-ascorbic acid may be useful for controlling body weight.


2017 ◽  
Vol 68 (7) ◽  
pp. 1481-1484 ◽  
Author(s):  
Radu Mihail Mirica ◽  
Mihai Ionescu ◽  
Alexandra Mirica ◽  
Octav Ginghina ◽  
Razvan Iosifescu ◽  
...  

Obesity involves the growth of adipose tissue cells (adipocytes and preadipocytes), as well as microvascular endothelial cells. Matrix metalloproteinases (MMPs) are relevant ezymes for the modulation of extracellular matrix (ECM) and adipocyte and preadipocytes differentiation. They are elevated in obese patients, generating abnormal ECM metabolism.[1]. This article proposes a thorough study of literature with focus on the important roles of matrix metalloproteinases in the pathophysiology of obesity. The article represents a narrative review based on an English-language PubMed research of the medical literature regardind important aspects of the proposed aim. MMP-2 activity was signi�cantly higher than MMP-9, both activities were detectable. MMP-9 was strongly correlated with body weight parameters before surgery, as well as after significant body weight reduction as a result of bariatric surgery. Concerning MMP-2 and MMP-9 they are also involved in the turnover of basement membranes both those of adipose tissue and endothelial. MMP-9 levels were moderately correlated with HDL cholesterol levels. Taken together, the present data suggest that changes in ECM through MMP-mediated degradation might play a critical role in the adipocyte differentiation process. These findings are detected both in clinical trials and in laboratory animal experiments. It is then tempting to speculate that the adipocyte-derived MMPs might represent a new pharmacological target for the inhibition of adipose tissue growth by inhibiting adipose differentiation as well as angiogenic process.


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