Independent Pseudogenizations and Losses of Sox15 During Amniote Diversification Following Asymmetric Ohnolog Evolution

Abstract Background: Four ohnologous genes (sox1, sox2, sox3, and sox15) were generated by two rounds of wholegenome duplication in a vertebrate ancestor. In eutherian mammals, Sox1, Sox2, and Sox3 participate in central nervous system (CNS) development. Sox15 functions in skeletal muscle regeneration, and has little functional overlap with the other three ohnologs. In contrast, Xenopus frog and zebrafish orthologs of sox15 as well as sox1-3s are expressed and function in CNS development. We previously reported that Sox15 is involved in mouse placental development as neofunctionalization, but is pseudogenized in marsupial opossum. These findings suggest that sox15 might have evolved with unusual gene fates during vertebrate evolution. However, knowledge concerning sox15 in other vertebrate lineages is scant. Our purpose was to clarify the fate and molecular evolution of sox15 during vertebrate evolution.Results: We searched for sox15 orthologs in various vertebrate lineages by homology and synteny analyses using vertebrate genome databases. Interestingly, sox15 was independently pseudogenized at least twice during species diversity in marsupial mammals. Moreover, we observed independent gene loss of sox15 at least twice during reptile evolution in squamates and crocodile-bird diversification. Codon-based phylogenetic tree and selective analyses revealed the highest dN/dS value for sox15 among the four ohnologs during jawed vertebrate evolution. The finding was supported by the high values in cartilaginous fishes, anuran amphibians, and amniotes. The high dN/dS value of sox15 may have been mainly caused by a relaxed selection. Marsupial and squamate sox15 may have evolved under more relaxed selection than those of eutherian mammals and testudine reptiles, respectively. Conclusions: The findings revealed an asymmetric evolution of sox15 among the four ohnologs during vertebrate evolution. Notably, independent pseudogenizations and losses of sox15 were observed during marsupial and reptile evolution, respectively. Both might have been caused by strong relaxed selection. The drastic gene fates of sox15, including neofunctionalization and pseudogenizations/losses during amniote diversification, might be caused by a release from evolutionary constraints. We discuss why sox15 has evolved under relaxed selection, considering the possible escapes from some constraints there could have been during its molecular evolution.

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Independent pseudogenizations and losses of sox15 during amniote diversification following asymmetric ohnolog evolution

BMC Ecology and Evolution ◽

10.1186/s12862-021-01864-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yusaku Ogita ◽

Kei Tamura ◽

Shuuji Mawaribuchi ◽

Nobuhiko Takamatsu ◽

Michihiko Ito

Keyword(s):

Sequence Similarity ◽

The Other ◽

Vertebrate Evolution ◽

Skeletal Muscle Regeneration ◽

Cns Development ◽

Placental Development ◽

Relaxed Selection ◽

Significant Sequence Similarity ◽

Anuran Amphibians ◽

Divergent Gene

Abstract Background Four ohnologous genes (sox1, sox2, sox3, and sox15) were generated by two rounds of whole-genome duplication in a vertebrate ancestor. In eutherian mammals, Sox1, Sox2, and Sox3 participate in central nervous system (CNS) development. Sox15 has a function in skeletal muscle regeneration and has little functional overlap with the other three ohnologs. In contrast, the frog Xenopus laevis and zebrafish orthologs of sox15 as well as sox1-3 function in CNS development. We previously reported that Sox15 is involved in mouse placental development as neofunctionalization, but is pseudogenized in the marsupial opossum. These findings suggest that sox15 might have evolved with divergent gene fates during vertebrate evolution. However, knowledge concerning sox15 in other vertebrate lineages than therian mammals, anuran amphibians, and teleost fish is scarce. Our purpose in this study was to clarify the fate and molecular evolution of sox15 during vertebrate evolution. Results We searched for sox15 orthologs in all vertebrate classes from agnathans to mammals by significant sequence similarity and synteny analyses using vertebrate genome databases. Interestingly, sox15 was independently pseudogenized at least twice during diversification of the marsupial mammals. Moreover, we observed independent gene loss of sox15 at least twice during reptile evolution in squamates and crocodile-bird diversification. Codon-based phylogenetic tree and selective analyses revealed an increased dN/dS ratio for sox15 compared to the other three ohnologs during jawed vertebrate evolution. Conclusions The findings revealed an asymmetric evolution of sox15 among the four ohnologs during vertebrate evolution, which was supported by the increased dN/dS values in cartilaginous fishes, anuran amphibians, and amniotes. The increased dN/dS value of sox15 may have been caused mainly by relaxed selection. Notably, independent pseudogenizations and losses of sox15 were observed during marsupial and reptile evolution, respectively. Both might have been caused by strong relaxed selection. The drastic gene fates of sox15, including neofunctionalization and pseudogenizations/losses during amniote diversification, might be caused by a release from evolutionary constraints.

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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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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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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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The Ontogeny and Function of Placental Macrophages

Frontiers in Immunology ◽

10.3389/fimmu.2021.771054 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jake R. Thomas ◽

Praveena Naidu ◽

Anna Appios ◽

Naomi McGovern

Keyword(s):

Human Placenta ◽

Outer Layer ◽

New Technologies ◽

Placental Development ◽

Fetal Health ◽

Hofbauer Cells ◽

Recent Developments ◽

Placental Macrophages ◽

And Function ◽

Insight Into

The placenta is a fetal-derived organ whose function is crucial for both maternal and fetal health. The human placenta contains a population of fetal macrophages termed Hofbauer cells. These macrophages play diverse roles, aiding in placental development, function and defence. The outer layer of the human placenta is formed by syncytiotrophoblast cells, that fuse to form the syncytium. Adhered to the syncytium at sites of damage, on the maternal side of the placenta, is a population of macrophages termed placenta associated maternal macrophages (PAMM1a). Here we discuss recent developments that have led to renewed insight into our understanding of the ontogeny, phenotype and function of placental macrophages. Finally, we discuss how the application of new technologies within placental research are helping us to further understand these cells.

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Abstract 17312: Hand1 Impairs Angiogenesis in Heart and Placenta

Circulation ◽

10.1161/circ.138.suppl_1.17312 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Jennifer A Courtney ◽

Helen N Jones

Keyword(s):

Histological Analysis ◽

Heart Defects ◽

Significant Risk ◽

Significant Risk Factor ◽

Placental Development ◽

Hypoplastic Left Heart ◽

Septal Defects ◽

And Function ◽

Left Heart Syndrome

Introduction: Congenital heart defects affect approximately 1% of live births, often requiring complex surgeries at birth. The most significant risk factor for surgery survival is birthweight. Proper placental development and function is vital for normal fetal growth. We have previously demonstrated abnormal placental development and vascularization in human CHD placentas. Hand1 has roles in heart and placental development and has been implicated in multiple types of CHD including double right outlet, hypoplastic left heart syndrome, and septal defects. We utilized the Hand1 A126fs/+ mouse to investigate the role of Hand1 in placentation and vascularization. Methods: Hand1 A126fs/+ female mice were time-mated with Nkx2.5cre or Cdh5cre males. Feto-placental units were harvested at E10.5 and E12.5 for histological analysis, vascular assessment by IHC for CD-31, and RNA expression by qPCR. Results: Nkx2.5cre/Hand1 a126fs/+ fetuses demonstrated embryonic lethality by E10.5 due to lack of placental labyrinth formation and vascularization (Figure 1). In contrast, ablation of Hand1 in vascular endothelium (Cdh5cre) did not disrupt placental labyrinth or heart at E12.5. Expression of VegFb, Ang1, Ang2, Flt1, Flk was reduced in Hand1 A126fs/+ ; Nkx2.5cre placentas compared to control littermates, but VegFa expression was increased. Conclusion: Our data demonstrate that Hand1 expression in placental trophoblast, but not endothelium, is necessary for vascularization of the labyrinth and may disrupt multiple angiogenic factors known to be expressed in trophoblast. Alterations in Hand1 may represent a mechanism for abnormal placentation in cases of CHD. Figure 1. H/E (A-C) and CD31 (D-F) images of Hand1 +/+ (A, D), Hand1 A126fs/+ ; Nkx2.5cre (B, E), and Hand1 A126fs/+ ; Cdh5cre (C, F) placentas at day E12.5. Hand1A 126fs/+ ; Nkx2.5cre placentas fail to form labyrinth and fetal vasculature, while Hand1 A126fs/+ ; Cdh5cre placentas develop normally at this timepoint.

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IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms21093302 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3302

Author(s):

Małgorzata Zimowska ◽

Karolina Archacka ◽

Edyta Brzoska ◽

Joanna Bem ◽

Areta M. Czerwinska ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Muscle Regeneration ◽

Structure And Function ◽

Skeletal Muscle Regeneration ◽

Stem Cell Markers ◽

Myogenic Factors ◽

And Function

Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.

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