Sex differences in modulation of fetoplacental vascular resistance in growth-restricted mouse fetuses following betamethasone administration: comparisons with human fetuses

Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; n = 8) and female (F; n = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [ Nω-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( P < 0.05) in female compared with male rats at 2 Hz [F: −33 ± 8% (SD); M: −26 ± 6%] but was not different at 5 Hz (F: −55 ± 7%; M: −47 ± 7%). During muscle contraction, evoked vasoconstriction was similar ( P > 0.05) in females and males at 2 Hz (F: −12 ± 5%; M: −13 ± 5%) but was blunted ( P < 0.05) in females compared with males at 5 Hz (F: −24 ± 5%; M: −34 ± 8%). l-NAME increased ( P < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( P < 0.05) in females compared with males; however, sympatholysis was not different ( P > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent. NEW & NOTEWORTHY Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.

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Analysis of Sex Differences in Skeletal Ossification and Variations in Near-term Mouse Fetuses

Congenital Anomalies ◽

10.1111/j.1741-4520.1990.tb00504.x ◽

1990 ◽

Vol 30 (2) ◽

pp. 145-149 ◽

Cited By ~ 1

Author(s):

Yukiko MANAKA ◽

Toshiaki WATANABE ◽

Akira ENDO

Keyword(s):

Sex Differences ◽

Near Term ◽

Mouse Fetuses ◽

Skeletal Ossification

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Effect of maternal betamethasone administration on feto-placental vascular resistance in the mouse†

Biology of Reproduction ◽

10.1093/biolre/ioz128 ◽

2019 ◽

Vol 101 (4) ◽

pp. 823-831 ◽

Cited By ~ 1

Author(s):

Lindsay S Cahill ◽

Clare L Whitehead ◽

Sebastian R Hobson ◽

Greg Stortz ◽

John C Kingdom ◽

...

Keyword(s):

Vascular Resistance ◽

Fetal Lung ◽

High Frequency Ultrasound ◽

Wave Reflections ◽

Antenatal Corticosteroids ◽

Vascular Abnormalities ◽

Fetal Lung Development ◽

Diastolic Velocity ◽

Acute Changes ◽

Mouse Fetuses

Abstract Antenatal corticosteroids are often administered to women at risk of preterm birth to accelerate fetal lung development; however, there is evidence that this treatment may adversely affect placental function in some fetuses. Our group has recently demonstrated that wave reflections in the umbilical artery (UA), measured using high-frequency ultrasound, are sensitive to placental vascular abnormalities. In the present study, we used this approach to investigate the effect of maternal administration of betamethasone, a clinically relevant corticosteroid, on the feto-placental vasculature of the mouse. Fetuses were assessed at embryonic day (E)15.5 and E17.5 in C57BL6/J mice. At both gestational ages, the UA diameter, UA blood flow, and the wave reflection coefficient were significantly elevated in the betamethasone-treated mice compared to vehicle-treated controls. These observations support the interpretation that placental vascular resistance dropped with betamethasone treatment to an extent that could not be explained by vasodilation of the UA alone. Consistent with clinical studies, the effect of betamethasone on UA end-diastolic velocity was heterogeneous. Our results suggest that UA wave reflections are more sensitive to acute changes in placental vascular resistance compared with the UA pulsatility index, and this technique may have clinical application to identify a favorable placental vascular response to fetal therapies such as antenatal corticosteroids, where the fetal heart rate is likely to vary.

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Sex differences in plasma corticosterone in mouse fetuses are mediated by differential placental transport from the mother and eliminated by maternal adrenalectomy or stress

Reproduction ◽

10.1530/jrf.0.0990283 ◽

1993 ◽

Vol 99 (2) ◽

pp. 283-290 ◽

Cited By ~ 64

Author(s):

M. M. Montano ◽

M-H. Wang ◽

F. S. vom Saal

Keyword(s):

Sex Differences ◽

Plasma Corticosterone ◽

Placental Transport ◽

Mouse Fetuses

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Volumetric Growth of the Liver in the Human Fetus: An Anatomical, Hydrostatic, and Statistical Study

BioMed Research International ◽

10.1155/2015/858162 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Michał Szpinda ◽

Monika Paruszewska-Achtel ◽

Alina Woźniak ◽

Celestyna Mila-Kierzenkowska ◽

Gabriela Elminowska-Wenda ◽

...

Keyword(s):

Sex Differences ◽

Early Diagnosis ◽

Statistical Study ◽

Liver Volume ◽

Strong Relationship ◽

Transverse Diameter ◽

Human Fetuses ◽

Volumetric Growth ◽

Sagittal Diameter ◽

Great Relevance

Using anatomical, hydrostatic, and statistical methods, liver volumes were assessed in 69 human fetuses of both sexes aged 18–30 weeks. No sex differences were found. The median of liver volume achieved by hydrostatic measurements increased from 6.57 cm3at 18–21 weeks through 14.36 cm3at 22–25 weeks to 20.77 cm3at 26–30 weeks, according to the following regression:y= −26.95 + 1.74×age ±Z ×(−3.15 + 0.27×age). The median of liver volume calculated indirectly according to the formula liver volume = 0.55×liver length×liver transverse diameter×liver sagittal diameter increased from 12.41 cm3at 18–21 weeks through 28.21 cm3at 22–25 weeks to 49.69 cm3at 26–30 weeks. There was a strong relationship (r=0.91,p<0.001) between the liver volumes achieved by hydrostatic (x) and indirect (y) methods, expressed byy= −0.05 + 2.16x ± 7.26. The liver volume should be calculated as follows liver volume = 0.26×liver length×liver transverse diameter×liver sagittal diameter. The age-specific liver volumes are of great relevance in the evaluation of the normal hepatic growth and the early diagnosis of fetal micro- and macrosomias.

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