Role of the uterine glands in the early embryonic death of mammals using a natural model: the plains viscacha Lagostomus maximus (Rodentia, Chinchillidae)

The histology of the endometrium has traditionally been established by observation of two-dimensional (2D) pathological sections. However, because human endometrial glands exhibit coiling and branching morphology, it is extremely difficult to obtain an entire image of the glands by 2D observation. In recent years, the development of three-dimensional (3D) reconstruction of serial pathological sections by computer and whole-mount imaging technology using tissue clearing methods with high-resolution fluorescence microscopy has enabled us to observe the 3D histoarchitecture of tissues. As a result, 3D imaging has revealed that human endometrial glands form a plexus network in the basalis, similar to the rhizome of grass, whereas mouse uterine glands are single branched tubular glands. This review summarizes the relevant literature on the 3D structure of mouse and human endometrium and discusses the significance of the rhizome structure in the human endometrium and the expected role of understanding the 3D tissue structure in future applications to systems biology.

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Uterine epithelial LIF receptors contribute to implantation chamber formation in blastocyst attachment

Endocrinology ◽

10.1210/endocr/bqab169 ◽

2021 ◽

Author(s):

Yamato Fukui ◽

Yasushi Hirota ◽

Tomoko Saito-Fujita ◽

Shizu Aikawa ◽

Takehiro Hiraoka ◽

...

Keyword(s):

Hormone Receptor ◽

Leukemia Inhibitory Factor ◽

Ovarian Hormones ◽

Signal Transducer ◽

Blastocyst Implantation ◽

Implantation Process ◽

Uterine Glands ◽

Transcription 3

Abstract Recent studies have demonstrated that the formation of an implantation chamber composed of a uterine crypt, an implantation-competent blastocyst, and uterine glands is a critical step in blastocyst implantation in mice. Leukemia inhibitory factor (LIF) activates signal transducer and activator of transcription 3 (STAT3) precursors via uterine LIF receptors (LIFRs), allowing successful blastocyst implantation. Our recent study revealed that the role of epithelial STAT3 is different from that of stromal STAT3. However, both are essential for blastocyst attachment, suggesting the different roles of epithelial and stromal LIFR in blastocyst implantation. However, how epithelial and stromal LIFR regulate the blastocyst implantation process remains unclear. To investigate the roles of LIFR in the uterine epithelium and stroma, we generated Lifr-floxed/lactoferrin (Ltf)-iCre (Lifr eKO) and Lifr-floxed/anti-Mullerian hormone receptor type 2 (Amhr2)-Cre (Lifr sKO) mice with deleted epithelial and stromal LIFR, respectively. Surprisingly, fertility and blastocyst implantation in the Lifr sKO mice were normal despite stromal STAT3 inactivation. In contrast, blastocyst attachment failed, and no implantation chambers were formed in the Lifr eKO mice with epithelial inactivation of STAT3. In addition, normal responsiveness to ovarian hormones was observed in the peri-implantation uteri of the Lifr eKO mice. These results indicate that the epithelial LIFR-STAT3 pathway initiates the formation of implantation chambers, leading to complete blastocyst attachment, and that stromal STAT3 regulates blastocyst attachment without stromal LIFR control. Thus, uterine epithelial LIFR is critical to implantation chamber formation and blastocyst attachment.

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Effects of 5-Fluorodeoxyuridine and Related Halogenated Pyrimidines on the Sand-Dollar Embryo

The Journal of Cell Biology ◽

10.1083/jcb.7.1.61 ◽

1960 ◽

Vol 7 (1) ◽

pp. 61-71 ◽

Cited By ~ 26

Author(s):

David A. Karnofsky ◽

Ross S. Basch

Keyword(s):

Embryonic Development ◽

Random Pattern ◽

Protective Agent ◽

Sand Dollar ◽

Blastula Stage ◽

Bacterial Dna ◽

Fluorinated Pyrimidines ◽

Minimal Lethal Concentration ◽

Embryonic Death

The embryo of the sand-dollar (Echinarachnius parma) was exposed to various concentrations of fluorinated pyrimidines immediately after fertilization. FUDR (5-fluorodeoxyuridine) was most active, and a concentration of 2 to 4 mγ/10 cc. (0.8 to 1.6 x 10-6 m.eq./liter) blocked development at the early blastula stage. Larger doses interrupted development at the same stage. This effect was prevented by thymidine (TDR) and thymine (T); and these pyrimidines protected against many times the minimal lethal concentration of FUDR. TDR was active as a protective agent if added just before early blastula formation. The other fluorinated pyrimidines, 5-fluorouracil (FU), 5-fluorouridine (FUR), 5-fluorocytidine (FCR), 5-fluorodeoxycytidine (FCDR), and 5-fluoroorotic acid (FO), were also studied. These drugs produced effects on embryonic development similar to those seen with FUDR. The effective concentrations, however, varied greatly. T and TDR provided protection against these drugs, but in most cases they were not so effective as against FUDR. 5-Bromodeoxyurdine (BrUDR), beginning at the early blastula stage, caused a random pattern of embryonic death up to the pluteus stage. This drug has been shown to be incorporated into bacterial DNA. BrUDR protected embryos against the early lethal effects of FUDR presumably acting as a thymidine substitute, but the embryos died subsequently in a pattern similar to that seen with BrUDR alone. FUDR and BrUDR appear to inhibit the formation and alter the structure of DNA, respectively, distinctive effects whch may provide a means for studying the role of DNA in embryonic development.

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The role of in bovine early embryonic death. II. Persistence of the organism in the uterus following intrauterine exposure

Theriogenology ◽

10.1016/0093-691x(86)90008-7 ◽

1986 ◽

Vol 26 (6) ◽

pp. 795-801 ◽

Cited By ~ 4

Author(s):

J.B. Kaneene ◽

C.D. Gibson ◽

P.H. Coe ◽

D.A. Morrow

Keyword(s):

Intrauterine Exposure ◽

Embryonic Death

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Prenatal development in Lagostomus maximus (Rodentia, Chinchillidae): A unique case among eutherian mammals of physiological embryonic death

Journal of Morphology ◽

10.1002/jmor.21341 ◽

2021 ◽

Vol 282 (5) ◽

pp. 720-732

Author(s):

Francisco Acuña ◽

Claudio G. Barbeito ◽

Enrique L. Portiansky ◽

María A. Miglino ◽

Mirta A. Flamini

Keyword(s):

Prenatal Development ◽

Unique Case ◽

Lagostomus Maximus ◽

Embryonic Death

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Severe dysregulation of TNF expression leads to multiple inflammatory diseases and embryonic death

10.1101/2020.05.28.120501 ◽

2020 ◽

Author(s):

Elise Clayer ◽

Destiny Dalseno ◽

Andrew Kueh ◽

Derek Lacey ◽

Minhsuang Tsai ◽

...

Keyword(s):

Transcriptional Regulation ◽

Inflammatory Diseases ◽

Regulatory Element ◽

Translational Efficiency ◽

Rapid Induction ◽

Regulation Mechanisms ◽

Post Transcriptional Regulation ◽

First Time ◽

Embryonic Death

AbstractPost-transcriptional regulation mechanisms regulate mRNA stability or translational efficiency via ribosomes and recent evidence indicates that it is a major determinant of the accurate levels of cytokine mRNAs. While transcriptional regulation of Tnf has been well studied and found to be important for the rapid induction of Tnf mRNA and regulation of the acute phase of inflammation, study of its post-transcriptional regulation has been largely limited to the role of the AU-rich element (ARE), and to a lesser extent, that of the constitutive decay element (CDE). We have identified a new regulatory element (NRE) in the 3’ untranslated region (3’UTR) of Tnf, and demonstrate that ARE, CDE and NRE cooperate to efficiently down regulate Tnf expression and prevent autoimmune inflammatory diseases. We also show for the first time that excessive TNF may lead to embryonic death.

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ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.764154 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li Duan ◽

Xiao Xu ◽

Limei Xu ◽

Caining Wen ◽

Kan Ouyang ◽

...

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Gene Knockouts ◽

Matrix Metabolism ◽

Or Gene ◽

Genetic Compensation ◽

Embryonic Death

Proteolytic targeting chimeras (PROTACs) is a rapid and reversible chemical knockout method. Compared with traditional gene-editing tools, it can avoid potential genetic compensation, misunderstandings caused by spontaneous mutations, or gene knockouts that lead to embryonic death. To study the role of estrogen receptor alpha (ERα) in the occurrence and progression of menopausal arthritis, we report a chemical knockout strategy in which stable peptide-based (PROTACs) against ERα to inhibit their function. This chemical knockdown strategy can effectively and quickly inhibit ERα protein in vivo and in vitro. In the rat menopausal arthritis model, this study showed that inhibiting estrogen function by degrading ERα can significantly interfere with cartilage matrix metabolism and cause menopausal arthritis by up-regulating matrix metalloproteinase (MMP-13). The results of this study indicate that ERα is a crucial estrogen receptor for maintaining cartilage metabolism. Inhibition of ERα function by PROTACs can promote the progression of osteoarthritis.

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Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation

10.1101/548511 ◽

2019 ◽

Author(s):

Jean-François Darrigrand ◽

Mariana Valente ◽

Pauline Martinez ◽

Glenda Comai ◽

Maxime Petit ◽

...

Keyword(s):

Neural Crest ◽

Bone Morphogenetic Proteins ◽

3D Imaging ◽

Neural Crest Cells ◽

Outflow Tract ◽

Bmp Signaling ◽

Pulmonary Artery Obstruction ◽

Artery Obstruction ◽

Embryonic Death

SummaryEstablishment of separated pulmonary and systemic circulations in vertebrates relies on the key role of neural crest cells (NCC) for the septation of the embryonic cardiac outflow tract (OFT). Absence of NCCs induces OFT septation defects, analogous to a loss of Bone Morphogenetic Proteins (BMPs) activity, though it remains unclear how BMPs control cardiac NCC differentiation and behaviour. To address this question, we monitored cardiac NCC state upon gain in BMP signaling, caused by the deletion of Dullard, using 3D-imaging and single cell transcriptomics. Specific loss of Dullard in the NCC results in premature OFT septation, pulmonary artery obstruction and embryonic death. This is caused by uncontrolled NCC convergence towards the endocardium and asymmetrical myocardial differentiation, promoted by elevated levels of the guiding cue Sema3c and decreased levels in mesenchymal trait markers. Furthermore, we unraveled the molecular basis of the zipper-like OFT septation where graded Sema3c expression follow a gradient of BMP activation in NCC along the OFT length.

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