scholarly journals Preeclampsia-Like Features and Partial Lactation Failure in Mice Lacking Cystathionine γ-Lyase—An Animal Model of Cystathioninuria

2019 ◽  
Vol 20 (14) ◽  
pp. 3507 ◽  
Author(s):  
Noriyuki Akahoshi ◽  
Hiroki Handa ◽  
Rintaro Takemoto ◽  
Shotaro Kamata ◽  
Masahide Yoshida ◽  
...  
Keyword(s):  
Late Pregnancy ◽  
Mammary Glands ◽  
Myoepithelial Cells ◽  
Receptor Expression ◽  
Wild Type ◽  
Normal Numbers ◽  
Milk Ejection ◽  
Blood Pressure Elevation ◽  
Pregnant Mice ◽  
Milk Ejection Reflex

Elevated plasma homocysteine levels are considered as a risk factor for cardiovascular diseases as well as preeclampsia—a pregnancy disorder characterized by hypertension and proteinuria. We previously generated mice lacking cystathionine γ-lyase (Cth) as cystathioninuria models and found them to be with cystathioninemia/homocysteinemia. We investigated whether Cth-deficient (Cth−/−) pregnant mice display any features of preeclampsia. Cth−/− females developed normally but showed mild hypertension (~10 mmHg systolic blood pressure elevation) in late pregnancy and mild proteinuria throughout development/pregnancy. Cth−/− dams had normal numbers of pups and exhibited normal maternal behavior except slightly lower breastfeeding activity. However, half of them could not raise their pups owing to defective lactation; they could produce/store the first milk in their mammary glands but not often provide milk to their pups after the first ejection. The serum oxytocin levels and oxytocin receptor expression in the mammary glands were comparable between wild-type and Cth−/− dams, but the contraction responses of mammary gland myoepithelial cells to oxytocin were significantly lower in Cth−/− dams. The contraction responses to oxytocin were lower in uteruses isolated from Cth−/− mice. Our results suggest that elevated homocysteine or other unknown factors in preeclampsia-like Cth−/− dams interfere with oxytocin that regulates milk ejection reflex.

EFFECT OF LOCALLY IMPLANTED OESTROGEN ON THE RESPONSE OF THE RAT'S LACTATING MAMMARY GLAND TO OXYTOCIN

1973 ◽  
Vol 73 (4) ◽  
pp. 700-712 ◽  
Author(s):  
J. D. Bruce ◽  
X. Cofre ◽  
V. D. Ramirez
Keyword(s):  
Mammary Gland ◽  
Mammary Glands ◽  
Myoepithelial Cells ◽  
Recording System ◽  
Saline Infusion ◽  
High Dose ◽  
Low Doses ◽  
Milk Ejection ◽  
Lactating Mammary Gland ◽  
Small Rise

ABSTRACT On the day following delivery (day 1 of lactation) one abdominal mammary gland was implanted with oestrogen and the contralateral gland received an empty needle. At 2, 5 or 10 days of lactation the rats were anaesthetized with pentobarbital and the nipples of both abdominal glands were cannulated and their pressures recorded by means of transducers coupled to an amplifier and recording system. The normal mammary glands of 5-day lactating rats responded to very low doses of oxytocin (Syntocinon®, Sandoz) (5× 10−8 mU) with a rhythmic elevation in pressure. However, saline infusion also evoked a small rise in intra-mammary pressure. Earlier (2 days) and later (10 days) in lactation the responses were smaller. Oestrogen decreases significantly the milk ejection response to oxytocin, and the effect was maximal at day 10 of lactation. Histological observations confirmed the diminished reaction of the gland to oxytocin, since the milk was retained in the alveoli of rats bearing a mammary-oestrogen implant. A paradoxical rise in pressure was detected in normal as well as in oestrogen-implanted glands when the lowest dose of oxytocin was injected in lactating rats which had previously received a high dose of oxytocin (50 mU or 500 mU). These results reinforce the hypothesis that oestrogen alters the milk ejection response to oxytocin and that the mechanism is probably related to changes in the contractility of the myoepithelial cells.

Reappraisal of the influence of mammary distension on the frequency of milk ejection in the rat

1985 ◽  
Vol 105 (1) ◽  
pp. 127-132
Author(s):  
C. M. Riggs ◽  
R. C. Sutherland ◽  
J. B. Wakerley
Keyword(s):  
Mammary Glands ◽  
Relative Amplitude ◽  
Milk Ejection ◽  
Behavioural Responses ◽  
Per Se ◽  
Milk Ejection Reflex

ABSTRACT Experiments were performed to reinvestigate the importance of mammary engorgement for activation of the milk-ejection reflex in the rat. Reflex milk ejection (measured by intramammary pressure recordings during a 2-h suckling test under anaesthesia) was compared in rats with engorged mammary glands (15-h separation from the pups, followed by sham-removal of milk) and in rats with drained mammary glands (15-h separation, followed by milk removal using a foster litter and exogenous oxytocin). In experiment 1, multiple small (2 mu.) doses of oxytocin were used for milk removal: these were effective in emptying the mammary glands and caused no subsequent impairment or change in sensitivity of the mammary response to oxytocin. Using this draining procedure, no significant differences were observed in either the number or relative amplitude of the milk ejections, or the occurrence of pup stretch reactions between engorged and drained rats. Similar results were seen in experiment 2, where an identical draining protocol was used, but the rats were pretreated with propranolol before the suckling test. In experiment 3, large (250 mu.) oxytocin doses were used for milk removal, as in previous studies. Again mammary draining had no effect on milk ejection in a subsequent suckling test (with propranolol pretreatment). However, the number of stretch reactions shown by the pups was significantly (P < 0·001) reduced from 8·6 ± 1·4/2 h to 1·9 ± 0·6/2 h. This effect probably related to long-term impairment of the oxytocin response of the mammary glands following the draining procedure, and could not be attributed to the draining per se. The dissociation of milk ejections and pup behavioural responses using this method of draining the glands explains previous reports, based on behavioural observations, that mammary draining profoundly disrupts milk ejection. It is concluded that mammary engorgement in fact has little influence on the activation of the milk-ejection reflex in the rat. J. Endocr. (1985) 105, 127–132

Decreased nuclear hormone receptor expression in the livers of mice in late pregnancy

2006 ◽  
Vol 290 (6) ◽  
pp. E1313-E1320 ◽  
Author(s):  
Trevor R. Sweeney ◽  
Arthur H. Moser ◽  
Judy K. Shigenaga ◽  
Carl Grunfeld ◽  
Kenneth R. Feingold
Keyword(s):  
Lipid Metabolism ◽  
Hormone Receptors ◽  
Target Genes ◽  
Serum Triglyceride ◽  
Late Pregnancy ◽  
Receptor Expression ◽  
Nuclear Hormone Receptors ◽  
Mrna Levels ◽  
Cholesterol Levels ◽  
Pregnant Mice

During the third trimester of pregnancy, there is an increase in serum triglyceride and cholesterol levels. The mechanisms accounting for these changes in lipid metabolism during pregnancy are unknown. We hypothesized that, during pregnancy, the expression of nuclear hormone receptors involved in regulating lipid metabolism would decrease. In 19-day pregnant mice, serum triglyceride and non-HDL cholesterol levels were significantly increased, whereas total cholesterol was slightly decreased, because of a decrease in the HDL fraction. Peroxisome proliferator-activated receptor (PPAR)α, PPARβ/δ, and PPARγ, liver X receptor (LXR)α and LXRβ, farnesoid X receptor (FXR), and retinoid X receptor (RXR)α, RXRβ, and RXRγ mRNA levels were significantly decreased in the livers of 19-day pregnant mice. Additionally, the expressions of thyroid receptor (TR)α, pregnane X receptor, sterol regulatory element-binding proteins (SREBP)-1a, SREBP-1c, SREBP-2, and liver receptor homolog 1 were also decreased, whereas the expression of TRβ, constitutive androstane receptor, and hepatic nuclear factor 4 showed no significant change. mRNA levels of the PPAR target genes carnitine-palmitoyl transferase 1α and acyl-CoA oxidase, the LXR target genes SREBP1c, ATP-binding cassettes G5 and G8, the FXR target gene SHP, and the TR target genes malic enzyme and Spot14 were all significantly decreased. Finally, the expressions of PPARγ coactivator (PGC)-1α and PGC-1β, known activators of a number of nuclear hormone receptors, were also significantly decreased. The decreases in expression of RXRs, PPARs, LXRs, FXR, TRs, SREBPs, and PGC-1s could contribute to the alterations in lipid metabolism during late pregnancy.

The winged helix gene,Foxb1, controls development of mammary glands and regions of the CNS that regulate the milk-ejection reflex

genesis ◽  
2001 ◽  
Vol 29 (2) ◽  
pp. 60-71 ◽  
Author(s):  
Jacqueline M. Kloetzli ◽  
Iris A. Fontaine-Glover ◽  
Erin R. Brown ◽  
Myrna Kuo ◽  
Patricia A. Labosky
Keyword(s):  
Mammary Glands ◽  
Milk Ejection ◽  
Winged Helix ◽  
Milk Ejection Reflex

THE ROLE OF THE NEUROHYPOPHYSIS IN THE MILK-EJECTION REFLEX

1952 ◽  
Vol 8 (2) ◽  
pp. 148-161 ◽  
Author(s):  
B. A. CROSS ◽  
G. W. HARRIS
Keyword(s):  
Intravenous Injection ◽  
Mammary Glands ◽  
Posterior Pituitary ◽  
Pituitary Extract ◽  
Active Process ◽  
Milk Ejection ◽  
Marked Diminution ◽  
Milk Ejection Reflex ◽  
Stimulation Of

1. Nursing and suckling behaviour of rabbits is described, and evidence given that an active process of milk ejection ('let-down') occurs in this as in other species. 2. Intravenous injection of posterior pituitary extracts in anaesthetized rabbits resulted in ejection of milk from a cannulated teat duct. The threshold dose was about 5 mU. and maximal responses were produced by 200 mU. of extract. Whole posterior pituitary extract was more effective than the oxytocic fraction, which was in turn more effective than the vasopressor fraction. 3. Stimulation of the supraopticohypophysial (s.o.h.) tract in anaesthetized rabbits also resulted in ejection of milk from a cannulated duct. Kymographic records of this response were similar to those obtained after injection of appropriate doses of posterior pituitary extract. 4. Lesions in the s.o.h. tract in lactating rabbits caused a marked diminution in the quantity of milk obtained by their litters in standard suckling tests, and incomplete evacuation of the mammary glands. Intravenous injection of posterior pituitary extract (30–200 mU.) into the does immediately before nursing gave a marked increase in the amount of milk obtained by the young and complete evacuation of the mammary glands. Stimulation of the region of the s.o.h. tract in these animals failed to elicit milk ejection from cannulated teat ducts. 5. Rabbits with hypothalamic lesions that did not involve the s.o.h. tract showed a normal milk-ejection reflex when suckled by their young, and a milk-ejection response after electrical stimulation of the s.o.h. tract.

scholarly journals Mex3c mutation affects lactation through impairing milk ejection in female mice

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Yong Du ◽  
Dongjun Sun ◽  
Yan Li
Keyword(s):  
Mammary Gland ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mammary Glands ◽  
Myoepithelial Cells ◽  
Mutant Mice ◽  
Milk Ejection ◽  
Female Mice ◽  
Antiviral Innate Immunity ◽  
Gland Development

Abstract Mouse Mex3c encodes RNA-binding proteins of variant length through alternative splicing. Its mutation results in multiple defects including growth retardation, perturbed energy balance, and defective antiviral innate immunity. Here we report that Mex3c mutation affects mammary gland development and lactation in female mice. Pups of Mex3c mutant dams die of starvation soon after birth. Milk contents are present in the alveoli but deficient in the ducts of the mammary glands in mutant mice. Mutant mice do not show prolactin or oxytocin deficiency. They also develop myoepithelial cells in the mammary glands. Mex3c is expressed in the mammary gland epithelium. Our data suggest that functional defects in mammary gland epithelium or myoepithelial cells could cause lactation defects.

scholarly journals Effects of Shiga Toxin 2 on Lethality, Fetuses, Delivery, and Puerperal Behavior in Pregnant Mice

2000 ◽  
Vol 68 (4) ◽  
pp. 2254-2258 ◽  
Author(s):  
Kazuaki Yoshimura ◽  
Jun Fujii ◽  
Akihide Tanimoto ◽  
Takashi Yutsudo ◽  
Masamichi Kashimura ◽  
...  
Keyword(s):  
Maternal Behavior ◽  
Shiga Toxin ◽  
Late Stage ◽  
Early Stage ◽  
Late Pregnancy ◽  
Normal Numbers ◽  
Major Virulence Factor ◽  
Shiga Toxin 2 ◽  
Pregnant Mice ◽  
Lethal Doses

ABSTRACT Shiga toxin 2 (Stx2) is produced by enterohemorrhagicEscherichia coli (EHEC) and is known as the major virulence factor of EHEC. The aim of this study was to evaluate the effects of Stx2 on (i) maternal lethality, (ii) fetuses, (iii) delivery period, and (iv) maternal behavior after delivery. Timed pregnant ICR mice were injected intravenously with Stx2 on day 5 of pregnancy (early stage) or on day 15 (late stage). In early-stage experiments, the number of normal fetuses of mice injected with Stx2 was significantly lower than that of control mice. In late-stage experiments, mothers injected with Stx2 delivered normal numbers of neonates, but could not take care of them. The lethal doses of Stx2 were not different for pregnant and nonpregnant female mice at either stage. We conclude that Stx2 is toxic to the fetus in early pregnancy and affects maternal puerperal behavior in late pregnancy.

Prolonged atrazine exposure beginning in utero and adult uterine morphology in mice

2021 ◽  
pp. 1-10
Author(s):  
Meaghan J. Griffiths ◽  
Amy L. Winship ◽  
Jessica M. Stringer ◽  
Elyse O. Swindells ◽  
Alesia P. Harper ◽  
...  
Keyword(s):  
Drinking Water ◽  
Oestrogen Receptor ◽  
Endometrial Hyperplasia ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Metabolism ◽  
In Utero ◽  
Receptor Expression ◽  
Mesenchymal Transition ◽  
Pregnant Mice ◽  
Emt Markers

Abstract Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5 mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5–9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.

scholarly journals Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safia Akhtar ◽  
Silas A. Culver ◽  
Helmy M. Siragy
Keyword(s):  
Protein Expression ◽  
High Fat Diet ◽  
Normal Diet ◽  
Receptor Expression ◽  
Wild Type ◽  
High Fat ◽  
Renal Gluconeogenesis ◽  
Mrna And Protein Expression ◽  
Polymerase Chain ◽  
Renal Expression

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.

MESENCEPHALIC AREAS CONTROLLING PULSATILE OXYTOCIN RELEASE IN THE SUCKLED RAT

1981 ◽  
Vol 91 (2) ◽  
pp. 233-244 ◽  
Author(s):  
T. S. JUSS ◽  
J. B. WAKERLEY
Keyword(s):  
Medial Geniculate Body ◽  
Milk Ejection ◽  
Ventral Tegmentum ◽  
Irregular Pattern ◽  
Oxytocin Release ◽  
Medial Geniculate ◽  
Radiofrequency Lesions ◽  
Milk Ejection Reflex ◽  
Bilateral Lesions ◽  
And Control

Experiments were performed on anaesthetized lactating rats to investigate the effects of radiofrequency lesions of the mesencephalon on the milk-ejection reflex. In lesioned and control rats, intramammary pressure recordings were used to estimate oxytocin release (number and relative amplitude of the intermittent milk-ejection responses) during a 3-h suckling test with ten pups. Bilateral lesions (diameter 0·5–1·5 mm) of the lateral tegmentum (near the brachium of the inferior colliculus and medial geniculate body) seriously disrupted the milk-ejection reflex, reducing the number of rats ejecting milk (two out of ten v. all 12 controls, P<0·001) and the amount of oxytocin they released (1·35±0·35 (s.e.m.) v. 15·52±2·19 mu. for controls, P<0·05). Unilateral lesions of the lateral tegmentum also impaired milk ejection and, if the suckling stimulus was restricted only to the contralateral nipples, oxytocin release was virtually abolished. Bilateral lesions placed more medially in the intermediate tegmentum were far less disruptive (eight out of nine rats ejected milk), though the amount of oxytocin released in this group (8·64±1·88 mu.) was still significantly (P<0·05) lower than controls. All rats with lesions of the central grey (nine) or ventral tegmentum (eight) displayed reflex milk ejection, as did those with multiple lesions of the tectum, central grey and ventral tegmentum (seven); in these three groups the amounts of oxytocin released (13·88±2·68, 13·10±1·90 and 11·04±1·95 mu. respectively) did not differ significantly from controls. Damage to the ventral tegmentum produced an irregular pattern of milk ejection characterized by occasional abnormally short (<2 min) milk-ejection intervals, though the overall number of responses in 3 h was less than that of controls (20·83±1·82 v. 14·50±1·30 mu., P<0·05). In conclusion, these results delineate two mesencephalic areas of particular importance in the milk-ejection reflex: (a) the lateral tegmentum, which appears to be concerned with transmission of the suckling stimulus from the contralateral nipples and is indispensable for oxytocin release, and (b) the ventral tegmentum which, although not an essential component of the reflex, may contribute to the timing of the intermittent milk-ejection responses.

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