SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 101A

Scientific Abstracts

ICC using (ab167413, Abcam at 1:250). Intensity of staining is expressed
as positive fractional area of a standard size field. Data expressed as
Mean±SEM and analyzed by ANOVA and two sample t test.
RESULTS: As shown on the left panel of the figure, we found a significant
increase in ICC staining for CYP11B2 in OM and LV in both sexes. The
GC effect, by magnitude, was significantly more pronounced in LV.
Supporting the ICC data is the fact that GC also was associated with a
significant increase in plasma ALDO in males and females (right panel
of Figure). Importantly, surgical reduction of OM fat mass significantly
attenuated the increase in plasma ALDO in GC-exposed. sheep.
*Figure(s) will be available online.
CONCLUSION: Our data strongly support the hypothesis that the
unfavorable intrauterine environment induced by the exposure to GC
alters the development of AT. We now present evidence that ALDO may
be a key player in the cardiometabolic phenotype present following fetal
programming. ALDO is known to promote cardiac hypertrophy, glucose
intolerance and hypertension, all features of Metabolic Syndrome which
are present in our model of fetal programming. Future studies will be
directed to assess ALDO effects in these particular organs. HL 68728
and HD 04784.

Vascular Function is Altered via Sex-Specific Mechanisms in Aged
Offspring Born from Dams of Advanced Maternal Age. Christy-Lynn
M Cooke*,2,3 Alison S Care,1 Raven D Kirshenman,2,3 Anita L Quon,2,3
Jude S Morton,2,3 Sandra T Davidge*.2,3 1The University of Adelaide,
Adelaide, Australia; 2University of Alberta, Edmonton, AB, Canada;
3
Women and Children's Health Research Institute, Edmonton, AB, Canada.
INTRODUCTION: The age at which women deliver their first child
has been steadily increasing. Advanced maternal age (≥35 years) is
associated with increased maternal and perinatal morbidity. Although
evidence suggests that the risk of adult onset cardiovascular disease
is increased in children born from compromised pregnancies, little is
known about the impact of advanced maternal age on developmental
programming in the offspring. We previously demonstrated that 4 month
old male, but not female rats from aged dams had impaired endotheliumdependent relaxation. Aging could be considered a 'second-hit' on the
cardiovascular system and may uncover an abnormal phenotype in a
susceptible population. We hypothesize that by 12 months of age, both
male and female offspring from advanced maternal aged dams will have
impaired vascular function and increased blood pressure compared to
offspring born from young dams.
METHODS: Female Sprague Dawley rats at 9.5 months of age (~35 years
in humans) as a model of advance maternal age and young female controls
were mated with young (4 month old) males. Male and female offspring
from young dams (YD) and aged dams (AD) were studied at 12 months
of age; assessments included blood pressure by tail cuff plethysmography
and vascular function in mesenteric arteries via wire myography.
RESULTS: Contrary to our hypothesis, male offspring from aged dams
had improved vascular function, with increased sensitivity to methacholine
(MCh pEC50: YD 7.4 ± 0.08 vs. AD 7.9 ± 0.11; P=0.007), while female
offspring were unaffected. This sex-specific effect may be due to an
enhanced PGHS-dependent vasodilator (such as prostacyclin) since only
male offspring from aged dams demonstrated a shift in MCh sensitivity
after pre-incubation with indomethacin (AD MCh pEC30 control vs. INDO:
8.2 ± 0.11 vs. 7.7 ± 0.06; P=0.004). Further, expression of prostacyclin
synthase by Western blot was significantly increased in vessels from male
offspring of aged dams. Although vascular function in female offspring
was not significantly impacted by maternal age, systolic blood pressure
was elevated in only female offspring from aged dams (YD: 125.3 ± 4.2
mmHg vs. AD: 144.0 ± 6.9 mmHg, P=0.03).
CONCLUSION: Offspring from aged dams demonstrate sex-specific
programming effects on cardiovascular function. Although our previous
study showed males to be particularly affected in young adulthood, at
12 months of age vasorelaxation was improved in male offspring from
aged dams, while aged female offspring were hypertensive. Given the

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increasing trend toward delayed parenthood, these findings may have
significant population and health care implications and warrant further
investigation.

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Role of Nephrogenesis in Developmental Programming of Adult Blood
Pressure and Nephron Number. Elizabeth DuPriest,1,3 Jessica Hebert†,1,2
Mayu Morita,1 Terry K Morgan*.1 1Oregon Health & Science University,
Portland, OR, United States; 2Portland State University, Portland, OR,
United States; 3Warner Pacific College, Portland, OR, United States.
INTRODUCTION: Fetal growth restriction (FGR) is linked to adultonset hypertension in a sex-specific manner; reduced nephrogenesis may
be causal. In a new developmental programming paradigm, we examine
genetically wild-type (WT) progeny of transgenic (TG) dams carrying an
extra copy of the angiotensinogen gene. Thus, we assessed nephrogenesis
in a TG mouse model with abnormal uterine spiral artery remodeling,
abnormal uteroplacental blood flow, and FGR. We hypothesized that FGR
pups would show sex differences in developing nephron susceptibility to
oxidative stress, nephrogenesis, and adult blood pressure.
METHODS: Transgenic B6.129P2-Tg (Agtdup) mice (Jackson labs)
were backcrossed for more than ten generations into a WT C57BL/6
background. WT progeny from TG dams and WT controls were studied
at fetal (18.5GD, n=6 TG, 6 WT litters), neonatal (2 wk, n= 4 TG, 6
WT litters) and adult (12 wk, n=6 TG, 6 WT litters) ages. Fetal kidney
oxidative stress was measured by pimonidazole incorporation (detected by
Hypoxyprobe immunostaining). Relative neonatal nephron number was
measured by counting all glomeruli per section in 4 longitudinal sections
per kidney, then adjusting mean glomerular number by mean (right, left)
kidney mass. In adults, blood pressure was measured by radiotelemetry,
and nephron number was also determined by stereometry.
RESULTS: Fetal progeny of TG dams were more likely to have
Hypoxyprobe positive renal tubules: 6/7, 86% of pups compared with
6/22, 27% (all weak staining) pups from WT controls (Fisher's Exact
p-value=0.01]. There was no sex difference. At 2 weeks of age, past
completion of nephrogenesis in mice, neonatal progeny of TG dams had
elevated glomerular number (P<0.001) compared with progeny from WT
dams. Adult males, but not females, from TG dams had elevated mean
arterial pressure (120 mmHg) and fewer nephrons by stereometry (30%
less) than WT controls.
CONCLUSION: In this FGR mouse model, sex differences in adult
nephron number and susceptibility to adult onset hypertension may
be related to nephron dropout after maturity, rather than differences in
prenatal or early postnatal nephrogenesis. Unexpectedly, oxidative stress
in proximal tubules of progeny of TG dams was not associated with
reduced nephrogenesis.

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Neurosteroid Therapy Following Preterm Birth in the Guinea
Pig Ameliorates Neurological Impairment. Julia Shaw†,1,2 Hannah
Palliser,1,2 Rebecca Dyson,3 Max Berry,3 Jonathan Hirst.1,2 1Hunter
Medical Research Institute, New Lambton Heights, Australia; 2University
of Newcastle, Callaghan, Australia; 3University of Otago, Wellington,
New Zealand.
INTRODUCTION: Prematurely born males in particular are at an
increased risk of developing attention deficit hyperactivity disorder
(ADHD) and learning difficulties during childhood. We have previously
shown that ex-preterm male juvenile guinea pigs exhibit a hyperactive
phenotype and reduced hippocampal and cerebellar myelination
(associated with learning and memory and motor deficits). The early
loss of placental allopregnanolone supply following preterm birth may
be involved. We propose that postnatal neurosteroid-replacement therapy
with an allopregnanolone analogue, ganaxolone (GNX), may prevent
deficits in neonatal development that contribute to these disorders.
METHODS: Pregnant guinea pigs were randomized to spontaneous term
birth (GA69; Term) or preterm induction of labour (GA62). Premature
pups received GNX (Prem-GNX, 2.5mg/kg sc) or vehicle (PremCON) twice daily until term equivalence. Open field and environment
exploration tests were performed at corrected postnatal age (CPNA)

Saturday Orals

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Reproductive Sciences Vol. 25, Supplement 1, March 2018

Table of Contents for the Digital Edition of SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018