Pregnancy depends on a delicate balance of immune activation and regulation

Exploration of Immunology ◽

10.37349/ei.2021.00031 ◽

2021 ◽

Author(s):

Shigeru Saito ◽

Akitoshi Nakashima ◽

Tomoko Shima ◽

Sayaka Tsuda

Keyword(s):

Fetal Growth ◽

Immune Tolerance ◽

Immune Activation ◽

Clinical Studies ◽

Immunocompetent Cells ◽

Implantation Failure ◽

Placental Development ◽

Delicate Balance

It is well recognized that immune tolerance is important to prevent semiallografted fetuses from rejection by maternal immunocompetent cells; however, immune activation also plays an important role in placental development and fetal growth. Basic and clinical studies have shown that an imbalance between immune activation and regulation can lead to implantation failure, miscarriage, and preeclampsia. Here, the balance between immunostimulation and immunoregulation in reproduction will be reviewed.

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Diabetes and pre-eclampsia affecting pregnancy: a retrospective cross-sectional study

Journal of Investigative Medicine ◽

10.1136/jim-2017-000537 ◽

2017 ◽

Vol 66 (4) ◽

pp. 728-732 ◽

Cited By ~ 1

Author(s):

Ram R Kalagiri ◽

Niraj Vora ◽

Jessica L Wilson ◽

Syeda H Afroze ◽

Venkata N Raju ◽

...

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Cross Sectional Study ◽

Growth Restriction ◽

Sectional Study ◽

Placental Development ◽

Cross Sectional ◽

Diabetes Status ◽

Elevated Glucose ◽

Post Hoc

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan’s post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally, patients with pre-existing diabetes who developed pre-eclampsia delivered smaller babies than those with pre-existing diabetes without pre-eclampsia (1.00±0.03, P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to fetal growth restriction. This outcome validates the understanding that elevated glucose earlier in pregnancy alters placentogenesis and leads to fetal growth restriction.

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Development of Structures and Transport Functions in the Mouse Placenta

Physiology ◽

10.1152/physiol.00001.2005 ◽

2005 ◽

Vol 20 (3) ◽

pp. 180-193 ◽

Cited By ~ 302

Author(s):

Erica D. Watson ◽

James C. Cross

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Cell Biology ◽

Fetal Death ◽

Nutrient Transport ◽

Growth Restriction ◽

Molecular Pathways ◽

Placental Development ◽

Mouse Mutants ◽

Mouse Placenta

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.

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FP075SEVERE HYPERTENSION DURING RAT PREGNANCY ALTERS PLACENTAL DEVELOPMENT AND FETAL GROWTH

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv168.06 ◽

2015 ◽

Vol 30 (suppl_3) ◽

pp. iii90-iii91

Author(s):

Gabriela Barrientos ◽

Ana Uceda ◽

Jorge Toblli

Keyword(s):

Fetal Growth ◽

Placental Development

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Regulation of Placental Development and Its Impact on Fetal Growth—New Insights From Mouse Models

Frontiers in Endocrinology ◽

10.3389/fendo.2018.00570 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 54

Author(s):

Laura Woods ◽

Vicente Perez-Garcia ◽

Myriam Hemberger

Keyword(s):

Mouse Models ◽

Fetal Growth ◽

Placental Development

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Placental development during early pregnancy in sheep: vascular growth and expression of angiogenic factors in maternal placenta

Reproduction ◽

10.1530/rep-09-0548 ◽

2010 ◽

Vol 140 (1) ◽

pp. 165-174 ◽

Cited By ~ 50

Author(s):

Anna T Grazul-Bilska ◽

Pawel P Borowicz ◽

Mary Lynn Johnson ◽

Megan A Minten ◽

Jerzy J Bilski ◽

...

Keyword(s):

Growth Factor ◽

Fetal Growth ◽

Early Pregnancy ◽

Vascular Development ◽

Hypoxia Inducible Factor ◽

Angiogenic Factors ◽

Placental Development ◽

Proliferating Cells ◽

Placental Angiogenesis ◽

Tissue Area

Placental vascular development (angiogenesis) is critical for placental function and thus for normal embryonic/fetal growth and development. Specific environmental factors or use of assisted reproductive techniques may result in poor placental angiogenesis, which may contribute to embryonic losses and/or fetal growth retardation. Uterine tissues were collected on days 14, 16, 18, 20, 22, 24, 26, 28, and 30 after mating and on day 10 after estrus (nonpregnant controls) to determine vascular development and expression of several factors involved in the regulation of angiogenesis in the endometrium. Compared with controls, several measurements of endometrial vascularity increased (P<0.001) including vascular labeling index (LI; proportion of proliferating cells), the tissue area occupied by capillaries, area per capillary (capillary size), total capillary circumference per unit of tissue area, and expression of factor VIII (marker of endothelial cells), but capillary number decreased (P<0.001). Compared with controls, mRNA for placental growth factor, vascular endothelial growth factor receptors, angiopoietins (ANGPT) 1 and 2, ANGPT receptorTEK, endothelial nitric oxide synthase, and hypoxia-inducible factor 1α increased (P<0.05) during early pregnancy. Vascular LI was positively correlated (P<0.05) with several measurements of vascularity and with mRNA expression of angiogenic factors. These data indicate that endometrial angiogenesis, manifested by increased vascularity and increased expression of several factors involved in the regulation of angiogenesis, is initiated very early in pregnancy. This more complete description of early placental angiogenesis may provide the foundation for determining whether placental vascular development is altered in compromised pregnancies.

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Effects of excess thromboxane A2 on placental development and nutrient transporters in a Mus musculus model of fetal growth restriction†

Biology of Reproduction ◽

10.1093/biolre/ioy006 ◽

2018 ◽

Vol 98 (5) ◽

pp. 695-704 ◽

Cited By ~ 3

Author(s):

Karen J Gibbins ◽

Katherine N Gibson-Corley ◽

Ashley S Brown ◽

Matthew Wieben ◽

Richard C Law ◽

...

Keyword(s):

Fetal Growth ◽

Mus Musculus ◽

Fetal Growth Restriction ◽

Thromboxane A2 ◽

Growth Restriction ◽

Nutrient Transporters ◽

Placental Development

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316. MATERNAL DIETARY ARGININE SUPPLEMENTATION DURING LATE GESTATION IMPROVES REPRODUCTIVE EFFICIENCY IN PIGS

Reproduction Fertility and Development ◽

10.1071/srb10abs316 ◽

2010 ◽

Vol 22 (9) ◽

pp. 116

Author(s):

M. J. De Blasio ◽

C. T. Roberts ◽

K. Kind ◽

R. Smits ◽

M. Nottle ◽

...

Keyword(s):

Blood Flow ◽

Birth Weight ◽

Fetal Growth ◽

Umbilical Vein ◽

Late Gestation ◽

Critical Periods ◽

Placental Development ◽

Pregnant Rats ◽

Growth And Survival ◽

Arginine Supplementation

Arginine (a non-essential amino acid) and its conversion to nitric oxide (NO) can promote formation of new blood vessels and cause vasodilation. This may reduce resistance and increase blood flow to the uterus and placenta, and the delivery of nutrients for fetal growth and survival. In pregnant rats, dietary arginine deficiency causes IUGR and increases fetal death and perinatal mortality, whereas dietary arginine supplementation reverses this. Human IUGR is associated with impaired NO synthesis, and eNOS activity in umbilical vein endothelial cells, but maternal arginine supplements have produced inconclusive results. We hypothesised that maternal arginine supplementation (MAS) in the pig (a species with naturally occurring IUGR), during late gestation, when placental angiogenesis and vascularity increase, would increase birth and placental weights. Large White (LW) and Landrace (LR) gilts (n = 285) and sows (n = 326), were fed either a control or arginine supplemented (+25 g/d arginine, Nutreco Progenos premix) diet (2.5 kg/d) in late gestation (d75-term at ~114 days). Number born, born alive, still born and mummified, birth weight and d10 weight of progeny were measured. Data were analysed using Univariate ANOVA. MAS in late gestation in gilts and sows reduced the number of still born (Con: 1.17 ± 0.13 piglets/litter; Arg: 0.84 ± 0.09 piglets/litter; P = 0.046). In LW gilts, MAS increased birth weight (Con: 1.21 ± 0.05kg; Arg: 1.34 ± 0.05kg; P < 0.05), and litter birth weight (Con: 13.38 ± 0.72 kg; Arg: 15.27 ± 0.73 kg; P < 0.05). MAS also increased birth weight in LW (Con: 1.17 ± 0.06 kg; Arg: 1.30 ± 0.06 kg; P < 0.05) and LR (Con: 1.47 ± 0.05 kg; Arg: 1.60 ± 0.05 kg; P < 0.05) sows, and reduced still borns in LW sows (Con: 1.12 ± 0.14 piglets/litter; Arg: 0.77 ± 0.09 piglets/litter; P < 0.05). MAS in late gestation improves pregnancy outcomes in terms of piglet survival and birth weight, in LW and LR gilts and sows. MAS during critical periods of placental development may enhance placental-fetal blood flow and nutrient transfer, thereby improving fetal growth and survival.

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Effects of vitrification and the superovulated environment on placental function and fetal growth in an IVF mouse model

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaaa047 ◽

2020 ◽

Vol 26 (8) ◽

pp. 624-635

Author(s):

C Roeca ◽

E Silva ◽

C Barentsen ◽

T L Powell ◽

T Jansson

Keyword(s):

Mouse Model ◽

Fetal Growth ◽

Gestational Age ◽

Large For Gestational Age ◽

Placental Development ◽

Developmental Potential ◽

Placental Function ◽

Uterine Environment ◽

Embryonic Viability ◽

Human Ivf

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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