SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 197A

Scientific Abstracts

aromatase activity. Daughters of T2D pregnant women are more insulin
resistant, have higher IGF-1 and AMH levels and lower adiponectin levels
at birth. Maternal insulin resistance is associated with elevated AMH and
insulin levels in the newborn. These data suggest that maternal T2D may
impair ovarian function and metabolic profile of their female offspring.
FONDECYT No 11.12146.

F-045

F-046
Obesity and Impaired Oocyte Developmental Competence: Bridging
Mouse and Human Studies. Kathleen O'Neill, Monica Mainigi, Teri Ord,
Yemin Lan, Rebecca Simmons. University of Pennsylvania, Philadelphia,
PA, United States.
INTRODUCTION: Obesity impairs oocyte development competence
in mice. Specifically, obesity results in increased apoptosis in cumulus
oocyte complexes and mitochondrial, meiotic spindle and chromosome
alignment abnormalities in the oocytes collected from obese mice. The
molecular mechanisms responsible are unknown. The aim of this study
was to use comprehensive, unbiased transcriptomic analyses to identify
novel transcripts and pathways that are altered by obesity and contribute
to oocyte dysfunction.
METHODS: Female C57BL/6J mice from 4-20 weeks of age were fed
control diet or a high-fat diet (HFD). Dams were primed with gonadotropin
and germinal vesicle oocytes (GVs) were isolated. GV transcriptional
status was assessed using Click-iT RNA. GVs were pooled (n=3 mice [60
GVs]/group, 4 biologic replicates in each group) and RNA-Seq libraries
were made using SMARTer Stranded Total RNA-Seq Kit - Pico Input
(Takara Bio USA). 50 million paired reads were obtained per sample.
Differentially expressed genes were identified using EdgeR and analyzed
with Ingenuity pathway analysis (IPA). GV oocytes were collected
from normoweight (n=6) and obese (n=9) women following ovarian
hyperstimulation and oocyte retrieval for the purposes of donor oocyte,
oocyte/embryo cryopreservation or in vitro fertilization. qPCR for select
genes identified as differentially expressed in obese mice was performed.
RESULTS: 11,085 transcripts were detected after filtering for read count
with RNA-Seq. 110 transcripts were differentially expressed using a FDR

197A

<0.05 and fold change ≥|2|. Exposure to a HFD altered genes involved in
apoptosis (WTAP, TP53, NEDD9, SIN3A, TNFAIP8, PSIP1, A4GALT,
OCN, RBL2, ANF274, EEF1D, TPR, NRF1, HYOU1, MPRIP, PECAM1,
SENP8, KDM2B) cell cycle regulation (RBL2, SIN3A, TP53, SSBP2),
microtubule dynamics (BBS9, MINK1, ODF3, PRICKLE2, RBFOX2,
TIAM1, TP53) and polar body extrusion (DNM2). qPCR confirmed
overexpression of all tested genes (BBS9, BUB3 and SSBP2) in an
independent cohort of pooled mouse oocytes (n=4 biologic replicates per
group) qPCR confirmed overexpression of BBS9 (p<0.05) and a trend
towards overexpression of BUB3 (p=0.06) in GV oocytes obtained from
obese women. Functional studies examining protein levels/location and
gene expression throughout oocyte and early embryo development are
currently underway.
CONCLUSION: Development of a functionally competent oocyte is
dependent upon normal formation of the meiotic spindle. Identification
of altered expression of genes vital to maintaining spindle stability and
DNA integrity in the setting of obesity is essential to unraveling the
mechanism underlying this relationship. Moreover the conservation of
gene expression changes identified in mice in human oocytes supports
the value of animal studies in understanding the mechanisms mediating
human disease processes.

F-047
Improvement of Periconception Nutrition and Lifestyle Behaviors
Using the mHealth Program Smarter Pregnancy: A Randomized
Controlled Trial. Elsje C Oostingh†, Maria PH Koster, Matthijs R van
Dijk, Sten P Willemsen, Eric AP Steegers, Joop SE Laven, Régine PM
Steegers-Theunissen, Erasmus University Medical Center, Rotterdam,
Netherlands.
INTRODUCTION: There is overwhelming evidence that healthy
maternal nutrition and lifestyle improve pregnancy chance in the IVF/
ICSI population. Therefore, we developed the mHealth coaching program
'Smarter Pregnancy' (www.smarterpregnancy.co.uk) to empower couples
to improve their nutrition and lifestyle behavior before and during
pregnancy. Here we investigate the compliance and effectiveness of the
Smarter Pregnancy program in the IVF/ICSI population.
METHODS: In the Netherlands a randomized controlled trial was
performed in couples with an indication for IVF/ICSI-treatment. At
baseline, screening on nutrition and lifestyle behaviors was performed.
These nutrition and lifestyle behaviors were translated into a dietary
risk score (DRS) comprising intake of folic acid, fruit and vegetables
and a lifestyle risk score (LRS) comprising smoking and alcohol use.
Both scores range from 0 to 9, a higher score denotes more inadequate
nutrition and lifestyle. In contrast to the control group, the intervention
group received personal online coaching based on intake of folic acid,
fruit and vegetables, smoking and alcohol use, and pregnancy status. A
linear regression model, based on difference-in-difference principle, was
used to measure differences in improvements in DRS and LRS between
the intervention and control group.
RESULTS: Overall compliance after 24 weeks of coaching was on
average 70% in the intervention- and 80% in the control group. After
adjustment for baseline risk scores, women (n=298) and men (n=103)
in the intervention group showed a significantly stronger decrease of the
DRS (β=0.453; 95%CI, 0.363-0.542 and β=0.232; 95%CI, 0.106-0.358,
respectively) and LRS (β=0.444; 95%CI, 0.339-0.549, β=0.233; 95%CI,
0.134-0.333, respectively) compared with women (n=309) and men
(n=111) in the control group. Serum folate and plasma homocysteine
concentrations are herewith largely in line.
CONCLUSION: The high compliance and effectiveness of mHealth
coaching in adopting adequate nutrition and lifestyle behavior in IVF/ICSI
couples emphasizes also it's possible clinical implications of contributing
to an increased chance of achieving pregnancy.
*Figure(s) will be available online.

Friday Posters

Adrenomedullin (ADM) is an Inhibitor of Insulin Synthesis in Human
Pancreatic β-Cells and Elevated ADM May Promote Development of
Gestational Diabetes Mellitus. Yuanlin Dong*, Manu Banadakoppa,
Meena Balakrishnan, Chandrasekhar Yallampalli. Baylor College of
Medicine/Texas Childrens Hospital, Houston, TX, United States.
INTRODUCTION: Defective adaptation of β-cells may play a
role in pathophysiology of Gestational diabetes mellitus (GDM) and
the molecular basis remains unclear. In this study, we explored if
adrenomedullin (ADM) is involved in defective β-cells adaptation by
assessing if ADM levels are elevated in GDM subjects and if ADM inhibits
insulin secretion by β-cells.
METHODS: MR-proADM, a stable gene product from ADM precursor,
levels were measured in plasma of pregnant women with normal glucose
tolerance (NGT) or GDM (n=10). The pancreatic β-Lox5 cell line, derived
from human β cells was transduced with homeodomain transcription
factor PDX-1 encoding lentiviral vector, and grown to form islet-like
aggregates. Aggregates were treated with ADM with or without its
antagonist ADM22-52 and insulin secretion and mRNA for ADM and
its receptors were measured.
RESULTS: Plasma MR-proADM levels were elevated in GDM relative
to NGT (Fig. 1, p=0.004). Aggregated pancreatic β-Lox5 cells express
mRNA for both ADM and its receptor components calcitonin receptor-like
receptor (CRLR) and receptor activity-modifying protein 2 (RAMP2).
ADM dose-dependently inhibits both insulin mRNA and secretion in
β-Lox5 cells (Fig. 2), and these inhibitions were reversed by ADM22-52
(p<0.05) and by cAMP-dependent PKA inhibitor and Erk inhibitor, but
not by PI-3K inhibitor.
CONCLUSION: ADM regulates insulin secretion in human pancreatic β
cells and the elevated plasma ADM levels in GDM subjects could inhibit
insulin synthesis and contribute to the pathogenesis of GDM.
*Figure(s) will be available online.

Reproductive Sciences Vol. 25, Supplement 1, March 2018
http://www.smarterpregnancy.co.uk
Table of Contents for the Digital Edition of SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018
