Albumin used in human IVF contain different levels of lipids and modify embryo and fetal growth in a mouse model

Abstract In studies of human IVF, as compared to frozen embryo transfer (ET), fresh ET is associated with smaller infants and higher risk of small for gestational age infants. Recent observations suggest that ET using vitrified embryos is associated with higher pregnancy and live birth rates compared to fresh ET, but increased rates of large for gestational age infants. The mechanisms underlying these associations are largely unknown, and available evidence suggests that the influence of IVF, vitrification and the superovulated (SO) uterine environment on placental function and fetal growth is complex. This warrants further investigation given the prevalent practice in human IVF of both fresh ET into a SO uterine environment, and vitrification with ET into a more physiologic uterine environment. Using a mouse model that closely resembles human IVF, we investigated if vitrification of IVF embryos better preserves placental function and results in better pregnancy outcomes as compared to fresh ET because of transfer into a more physiologic endometrium. We found that the SO environment, independent of vitrification status, reduced implantation rates, inhibited placental mechanistic target of rapamycin signaling and induced placental stress signaling, resulting in fetal growth restriction (1.080 ± 0.05 g estrous fresh (n = 17 litters), 1.176 ± 0.05 g estrous vitrified (n = 12), 0.771 ± 0.06 g SO fresh (n = 15), 0.895 ± 0.08 g SO vitrified (n = 10), P < 0.0001). In addition, our study suggests that vitrification impairs the developmental potential of IVF blastocysts that resulted in a significantly smaller litter size (2.6 ± 2.3 fresh estrous vs 2.5 ± 2.4 fresh SO vs 1.6 ± 1.7 estrous vitrified vs 1.7 ± 1.8 SO vitrified, P = 0.019), with no effect on fetal growth or placental function at term. Our findings suggest that vitrification may negatively impact early embryonic viability, while the SO maternal uterine environment impairs both placental development and fetal growth in IVF.

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Impaired fetal organ development is linked to altered placental morphology and function in a systemic hsFLT1-transgenic preeclampsia/fetal growth restriction mouse model: the placenta as a modulator of offspring health?

Placenta ◽

10.1016/j.placenta.2021.07.085 ◽

2021 ◽

Vol 112 ◽

pp. e26

Author(s):

Rebekka Vogtmann ◽

Meray Serdar ◽

Monia Dewan ◽

Gemma Comas-Armangué ◽

Mian Bao ◽

...

Keyword(s):

Mouse Model ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Growth Restriction ◽

Organ Development ◽

Fetal Organ ◽

And Function ◽

Offspring Health

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Understanding the placental mechanisms underpinning increased fetal growth in a mouse model of FGR following sildenafil citrate treatment: Insight from network analyses

Placenta ◽

10.1016/j.placenta.2015.07.214 ◽

2015 ◽

Vol 36 (9) ◽

pp. A9-A10

Author(s):

Adam Stevens ◽

Richard Unwin ◽

Nitin Rustogi ◽

Andrew Dowsey ◽

Garth Cooper ◽

...

Keyword(s):

Mouse Model ◽

Fetal Growth ◽

Sildenafil Citrate ◽

Network Analyses

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Bisphenol-A (BPA) exposure on the day of implantation alters uterine epigenome disrupting fetal growth: a mouse model

Fertility and Sterility ◽

10.1016/j.fertnstert.2016.07.043 ◽

2016 ◽

Vol 106 (3) ◽

pp. e12

Author(s):

I. Robertshaw ◽

J.M. Sroga ◽

M.A. Thomas

Keyword(s):

Mouse Model ◽

Bisphenol A ◽

Fetal Growth

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Cigarette exposure induces changes in maternal vascular function in a pregnant mouse model

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00274.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. R1249-R1256 ◽

Cited By ~ 9

Author(s):

Robin E. Gandley ◽

Arun Jeyabalan ◽

Ketaki Desai ◽

Stacy McGonigal ◽

Jennifer Rohland ◽

...

Keyword(s):

Mouse Model ◽

Cigarette Smoke ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Smoke Exposure ◽

Renal Arteries ◽

Growth Restriction ◽

Whole Body ◽

Cigarette Smoke Exposure ◽

Pregnant Mice

Smoking is associated with multiple adverse pregnancy outcomes, including fetal growth restriction. The objective of this study was to determine whether cigarette smoke exposure during pregnancy in a mouse model affects the functional properties of maternal uterine, mesenteric, and renal arteries as a possible mechanism for growth restriction. C57Bl/CJ mice were exposed to whole body sidestream smoke for 4 h/day. Smoke particle exposure was increased from day 4 of gestation until late pregnancy ( day 16–19), with mean total suspended particle levels of 63 mg/m3, representative of moderate-to-heavy smoking in humans. Uterine, mesenteric, and renal arteries from late-pregnant and virgin mice were isolated and studied in a pressure-arteriograph system ( n = 23). Plasma cotinine was measured by ELISA. Fetal weights were significantly reduced in smoke-exposed compared with control fetuses (0.88 ± 0.1 vs. 1.0 ± 0.08 g, P < 0.02), while litter sizes were not different. Endothelium-mediated relaxation responses to methacholine were significantly impaired in both the uterine and mesenteric vasculature of pregnant mice exposed to cigarette smoke during gestation. This difference was not apparent in isolated renal arteries from pregnant mice exposed to cigarette smoke; however, relaxation was significantly reduced in renal arteries from smoke-exposed virgin mice. In conclusion, we found that passive cigarette smoke exposure is associated with impaired vascular relaxation of uterine and mesenteric arteries in pregnant mice. Functional maternal vascular perturbations during pregnancy, specifically impaired peripheral and uterine vasodilation, may contribute to a mechanism by which smoking results in fetal growth restriction.

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Placental and fetal characteristics of the Ohia mouse line recapitulate outcomes in human hypoplastic left heart syndrome

10.1101/2020.08.17.252387 ◽

2020 ◽

Author(s):

Rebecca L Wilson ◽

Weston Troja ◽

Jennifer Courtney ◽

Helen N Jones

Keyword(s):

Mouse Model ◽

Mrna Expression ◽

Hypoplastic Left Heart Syndrome ◽

Fetal Growth ◽

Fetal Weight ◽

Left Heart ◽

Heterozygous Genotype ◽

Placental Development ◽

Hypoplastic Left Heart ◽

Left Heart Syndrome

AbstractCongenital heart defects (CHDs) are one of the most common birth defects worldwide. The morbidity and mortality associated with these defects is compounded by increased frequency of fetal growth abnormalities in the newborns. Inappropriate placental development and function has been implicated as a contributing factor to poor fetal growth in pregnancies complicated by CHDs however, the exact mechanisms are poorly understood. In the Ohia mouse model of hypoplastic left heart syndrome (HLHS), the double homozygous genotype had previously been shown to be embryonically lethal at mid-pregnancy; a time in which optimal establishment of the placenta is crucial to fetal survival. We aimed to characterize placental and fetal growth and development in the double heterozygous genotype to determine whether the genetic mutations associated with HLHS in the Ohia mouse also affect the placenta. The frequency of fetuses with reduced weight near term was shifted in the double heterozygous genotype compared to wildtype fetuses. This shift in fetal weight distribution was associated with reduced fetal capillary density in the placentas of the double heterozygotes as well as a reduction in placental mRNA expression of angiogenic factors placenta growth factor (Pgf) and fms-like tyrosine kinase-1 (Flt1) suggesting abhorrent placental angiogenesis. Positive correlations were observed between fetal weight and placenta mRNA expression of several nutrient transporters in the double heterozygous genotype but not observed in the wildtype. This data shows changes to placental angiogenesis and nutrient transport that are likely to contribute to inadequate fetal growth in the Ohia mouse model. Such differences are similar to findings in studies of human placentas from pregnancies with a fetus with HLHS and highlights the importance of this mouse model in continuing to understand the link between placental development and CHDs such as HLHS.New and NoteworthyWe used the Ohia mouse line, which is characterized with a hypoplastic left heart syndrome (HLHS)-like phenotype to investigate the contribution of placental development and function to fetal growth abnormalities associated with congenital heart defects (CHDs). We demonstrate an increase in the frequency of fetuses with lower fetal weight in the double heterozygous genotype which is associated with abnormalities to the placental microstructure, reduced placental fetal capillary density and placental mRNA expression of angiogenic factors Pgf and Flt1. These results are supported by similar studies of human placentas from HLHS pregnancies and highlights the usefulness of this model in furthering our understanding of abnormal fetal growth in CHDs.

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