Animal Models to Study Placental Development and Function throughout Normal and Dysfunctional Human Pregnancy

Here a survey of placental evolution is conducted. Placentation is a key factor for the evolution of placental mammals that had evolved an astonishing diversity. As a temporary organ that does not allow easy access, it is still not well understood. The lack of data also is a restriction for better understanding of placental development, structure, and function in the human. Animal models are essential, because experimental access to the human placenta is naturally restricted. However, there is not a single ideal model that is entirely similar to humans. It is particularly important to establish other models than the mouse, which is characterised by a short gestation period and poorly developed neonates that may provide insights only for early human pregnancy. In conclusion, current evolutionary studies have contributed essentially to providing a pool of experimental models for recent and future approaches that may also meet the requirements of a long gestation period and advanced developmental status of the newborn in the human. Suitability and limitations of taxa as alternative animal models are discussed. However, further investigations especially in wildlife taxa should be conducted in order to learn more about the full evolutionary plasticity of the placenta system.

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Modeling Human Peri-implantation Placental Development and Function

Biology of Reproduction ◽

10.1093/biolre/ioab080 ◽

2021 ◽

Author(s):

J Zhou ◽

R C West ◽

E L Ehlers ◽

T Ezashi ◽

L C Schulz ◽

...

Keyword(s):

In Vitro Models ◽

Tissue Cultures ◽

Placental Development ◽

Blastocyst Culture ◽

Human Pregnancy ◽

Immortalized Cell ◽

And Function ◽

Implantation Period ◽

Trophoblast Culture

Abstract It is very difficult to gain a better understanding of the events in human pregnancy that occur during and just after implantation because such pregnancies are not yet clinically detectable. Animal models of human placentation are inadequate. In vitro models that utilize immortalized cell lines and cells derived from trophoblast cancers have multiple limitations. Primary cell and tissue cultures often have limited lifespans and cannot be obtained from the peri-implantation period. We present here two contemporary models of human peri-implantation placental development: extended blastocyst culture and stem-cell derived trophoblast culture. We discuss current research efforts that employ these models and how such models might be used in the future to study the “black box” stage of human pregnancy.

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Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

Current Vascular Pharmacology ◽

10.2174/1570161118666200616144512 ◽

2020 ◽

Vol 19 (2) ◽

pp. 176-192

Author(s):

Samantha Bedell ◽

Janine Hutson ◽

Barbra de Vrijer ◽

Genevieve Eastabrook

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Maternal Obesity ◽

Environmental Changes ◽

Current Knowledge ◽

Therapeutic Interventions ◽

Placental Development ◽

Exchange Site ◽

And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

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Foraging with the frontal cortex: A cross-species evaluation of reward-guided behavior

Neuropsychopharmacology ◽

10.1038/s41386-021-01140-0 ◽

2021 ◽

Cited By ~ 1

Author(s):

Peter H. Rudebeck ◽

Alicia Izquierdo

Keyword(s):

Animal Models ◽

Frontal Cortex ◽

Psychiatric Disorders ◽

Similarities And Differences ◽

And Function ◽

Future Work ◽

Intense Debate

AbstractEfficient foraging is essential to survival and depends on frontal cortex in mammals. Because of its role in psychiatric disorders, frontal cortex and its contributions to reward procurement have been studied extensively in both rodents and non-human primates. How frontal cortex of these animal models compares is a source of intense debate. Here we argue that translating findings from rodents to non-human primates requires an appreciation of both the niche in which each animal forages as well as the similarities in frontal cortex anatomy and function. Consequently, we highlight similarities and differences in behavior and anatomy, before focusing on points of convergence in how parts of frontal cortex contribute to distinct aspects of foraging in rats and macaques, more specifically. In doing so, our aim is to emphasize where translation of frontal cortex function between species is clearer, where there is divergence, and where future work should focus. We finish by highlighting aspects of foraging for which have received less attention but we believe are critical to uncovering how frontal cortex promotes survival in each species.

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A Potential Role and Contribution of Androgens in Placental Development and Pregnancy

Life ◽

10.3390/life11070644 ◽

2021 ◽

Vol 11 (7) ◽

pp. 644

Author(s):

Agata M. Parsons ◽

Gerrit J. Bouma

Keyword(s):

Fetal Development ◽

Fetal Loss ◽

Membrane Receptors ◽

Placental Development ◽

Placental Function ◽

Fetal Physiology ◽

Estrogen Synthesis ◽

And Function ◽

Pregnancy Disorders

Successful pregnancy requires the establishment of a highly regulated maternal–fetal environment. This is achieved through the harmonious regulation of steroid hormones, which modulate both maternal and fetal physiology, and are critical for pregnancy maintenance. Defects in steroidogenesis and steroid signaling can lead to pregnancy disorders or even fetal loss. The placenta is a multifunctional, transitory organ which develops at the maternal–fetal interface, and supports fetal development through endocrine signaling, the transport of nutrients and gas exchange. The placenta has the ability to adapt to adverse environments, including hormonal variations, trying to support fetal development. However, if placental function is impaired, or its capacity to adapt is exceeded, fetal development will be compromised. The goal of this review is to explore the relevance of androgens and androgen signaling during pregnancy, specifically in placental development and function. Often considered a mere precursor to placental estrogen synthesis, the placenta in fact secretes androgens throughout pregnancy, and not only contains the androgen steroid nuclear receptor, but also non-genomic membrane receptors for androgens, suggesting a role of androgen signaling in placental function. Moreover, a number of pregnancy disorders, including pre-eclampsia, gestational diabetes, intrauterine growth restriction, and polycystic ovarian syndrome, are associated with abnormal androgen levels and androgen signaling. Understanding the role of androgens in the placenta will provide a greater understanding of the pathophysiology of pregnancy disorders associated with androgen elevation and its consequences.

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Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽

10.3390/mi12080884 ◽

2021 ◽

Vol 12 (8) ◽

pp. 884

Author(s):

Marta Cherubini ◽

Scott Erickson ◽

Kristina Haase

Keyword(s):

Drug Testing ◽

Cell Types ◽

In Vitro Models ◽

Placental Development ◽

Scientific Challenge ◽

Induced Pluripotent ◽

And Function ◽

And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

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Recent Advance in the Relationship between Excitatory Amino Acid Transporters and Parkinson’s Disease

Neural Plasticity ◽

10.1155/2016/8941327 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Yunlong Zhang ◽

Feng Tan ◽

Pingyi Xu ◽

Shaogang Qu

Keyword(s):

Parkinson’S Disease ◽

Amino Acid ◽

Animal Models ◽

Substantia Nigra ◽

Excitatory Amino Acid ◽

Synaptic Cleft ◽

Dopamine Neurons ◽

Amino Acid Transporters ◽

Excitatory Amino Acid Transporters ◽

And Function

Parkinson’s disease (PD) is the most common movement disorder disease in the elderly and is characterized by degeneration of dopamine neurons and formation of Lewy bodies. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). If glutamate is not removed promptly in the synaptic cleft, it will excessively stimulate the glutamate receptors and induce excitotoxic effects on the CNS. With lack of extracellular enzyme to decompose glutamate, glutamate uptake in the synaptic cleft is mainly achieved by the excitatory amino acid transporters (EAATs, also known as high-affinity glutamate transporters). Current studies have confirmed that decreased expression and function of EAATs appear in PD animal models. Moreover, single unilateral administration of EAATs inhibitor in the substantia nigra mimics several PD features and this is a solid evidence supporting that decreased EAATs contribute to the process of PD. Drugs or treatments promoting the expression and function of EAATs are shown to attenuate dopamine neurons death in the substantia nigra and striatum, ameliorate the behavior disorder, and improve cognitive abilities in PD animal models. EAATs are potential effective drug targets in treatment of PD and thus study of relationship between EAATs and PD has predominant medical significance currently.

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Abstract 228: Alterations of Cardiac Morphology and Function Caused by Cardio-Thoracic Surgery in Small Animal Models of Heart Disease

Circulation Research ◽

10.1161/res.113.suppl_1.a228 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Peter Nordbeck ◽

Leoni Bönhof ◽

Karl-Heinz Hiller ◽

Sabine Voll ◽

Paula Arias ◽

...

Keyword(s):

Body Weight ◽

Heart Disease ◽

Animal Models ◽

Right Ventricular ◽

Small Animal ◽

Cardiac Morphology ◽

Small Animal Models ◽

And Function

Background: Surgical procedures in small animal models of heart disease, such as artificial ligation of the coronary arteries for experimental myocardial infarction, can evoke alterations in cardiac morphology and function. Such alterations might induce artificial early or long term effects in vivo that might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies in small animal models of heart disease. Methods: Female Wistar rats were matched for weight and distributed to sham left coronary artery ligation or untreated control. Cardiac parameters were then investigated in vivo by high-field MRI over time after the surgical procedure, determining left and right ventricular morphology and function. Additionally, the time course of several metabolic and inflammatory blood parameters was determined. Results: Rats after sham surgery showed a lower body weight for up to 8 weeks after the intervention compared to healthy controls. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in the sham operated rats compared to the controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed prolonged metabolic and inflammatory changes after surgery not related to cardiac disease. Conclusion: There is a small distinct impact of cardio-thoracic surgical procedures on the global integrity of the organism, which in the long term also includes circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective studies and transferring the findings to conditions in patients.

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Animal Models of Down Syndrome

The Oxford Handbook of Down Syndrome and Development ◽

10.1093/oxfordhb/9780190645441.013.4 ◽

2021 ◽

Author(s):

Anna J. Moyer ◽

Roger H. Reeves

Keyword(s):

Down Syndrome ◽

Cognitive Impairment ◽

Intellectual Disability ◽

Animal Models ◽

Brain Regions ◽

Laboratory Mice ◽

Tremendous Progress ◽

New Treatments ◽

And Function ◽

Early Developmental

Is intellectual disability a treatable feature of persons with Down syndrome? Researchers have made tremendous progress in the last 30 years, from creating the first mouse model of Down syndrome to completing the first major clinical trial for cognitive impairment in people with Down syndrome. Until recently, normalizing brain development and function seemed too lofty a goal, and indeed, even proposing a candidate therapy requires answering a number of difficult questions. How does trisomy 21, a molecular diagnosis, cause the clinical phenotypes of Down syndrome? When, where, and how do trisomic genes act to disrupt normal development and which genes are involved with which outcomes? Which brain regions and behaviors are most impaired? Is there an early developmental window of time during which treatments are most effective? This article discusses how animal models such as laboratory mice can be used to understand intellectual disability and to develop new treatments for cognitive impairment.

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Epigenetics of Placental Development and Function

The Guide to Investigation of Mouse Pregnancy ◽

10.1016/b978-0-12-394445-0.00024-2 ◽

2014 ◽

pp. 285-295

Author(s):

Shuhei Ito ◽

Mitsuko Hirosawa ◽

Koji Hayakawa ◽

Shintaro Yagi ◽

Satoshi Tanaka ◽

...

Keyword(s):

Placental Development ◽

And Function

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