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Abstract During embryo implantation, blastocyst interacts with the receptivity endometrium and the endometrial epithelium secretes nurturing fluid to support embryonic development. Interferon-λ (IFN-λ) is a novel, non-redundant regulator that participates in the fetal–maternal interaction; however, the precise molecular mechanism underlying its impact on uterine receptivity remains elusive. Here, microarray profiling revealed that 149 specific miRNAs were differentially expressed in the human endometrial cells following IFN-λ treatment. In particular, miR-124-3p expression was significantly reduced after IFN-λ treatment (p

During embryo implantation, blastocyst interacts with the receptivity endometrium and the endometrial epithelium secretes nurturing fluid to support embryonic development. Interferon-λ (IFN-λ) is a novel, non-redundant regulator that participates in the fetal–maternal interaction; however, the precise molecular mechanism underlying its impact on uterine receptivity remains elusive. Here, microarray profiling revealed that 149 specific miRNAs were differentially expressed in the human endometrial cells following IFN-λ treatment. In particular, miR-124-3p expression was significantly reduced after IFN-λ treatment (p < 0.05). An in vivo mouse pregnancy model showed that miR-124-3p overexpression notably decreased embryo implantation rate and led to an aberrant epithelial phenotype. Furthermore, miR-124-3p negatively impacted the migration and proliferation of endometrial cells, and hindered embryonic developmental competence in terms of blastocyst formation and global DNA re-methylation. Downstream analysis showed that LIF, MUC1 and BCL2 are potential target genes for miR-124-3p, which was confirmed using western blotting and immunofluorescence assays. In conclusion, IFN-λ-driven downregulation of miR-124-3p during embryo implantation modulates uterine receptivity. The dual functional role of miR-124-3p suggests a cross-talk model wherein, maternal endometrial miRNA acts as a transcriptomic modifier of the peri-implantation endometrium and embryo development. [ABSTRACT FROM AUTHOR]

Mitochondrial remodeling during the peri-implantation stage is the hallmark event essential for normal embryogenesis. Among the changes, enhanced oxidative phosphorylation is critical for supporting high energy demands of postimplantation embryos, but increases mitochondrial oxidative stress, which in turn threatens mitochondrial DNA (mtDNA) stability. However, how mitochondria protect their own histone-lacking mtDNA, during this stage remains unclear. Concurrently, the mitochondrial genome gain DNA methylation by this stage. Its spatiotemporal coincidence with enhanced mitochondrial stress led us to ask if mtDNA methylation has a role in maintaining mitochondrial genome stability. Herein, we report that mitochondrial genome undergoes de novo mtDNA methylation that can protect mtDNA against enhanced oxidative damage during the peri-implantation window. Mitochondrial genome gains extensive mtDNA methylation during transition from blastocysts to postimplantation embryos, thus establishing relatively hypermethylated mtDNA from hypomethylated state in blastocysts. Mechanistic study revealed that DNA methyltransferase 3A (DNMT3A) and DNMT3B enter mitochondria during this process and bind to mtDNA, via their unique mitochondrial targeting sequences. Importantly, loss- and gain-of-function analyses indicated that DNMT3A and DNMT3B are responsible for catalyzing de novo mtDNA methylation, in a synergistic manner. Finally, we proved, in vivo and in vitro, that increased mtDNA methylation functions to protect mitochondrial genome against mtDNA damage induced by increased mitochondrial oxidative stress. Together, we reveal mtDNA methylation dynamics and its underlying mechanism during the critical developmental window. We also provide the functional link between mitochondrial epigenetic remodeling and metabolic changes, which reveals a role for nuclear-mitochondrial crosstalk in establishing mitoepigenetics and maintaining mitochondrial homeostasis.

Abstract Background One of the most critical periods for the loss of pig embryos is the 12th day of gestation when implantation begins. Recent studies have shown that non-coding RNAs (ncRNAs) play important regulatory roles during pregnancy. Circular RNAs (circRNAs) are a kind of ubiquitously expressed ncRNAs that can directly regulate the binding proteins or regulate the expression of target genes by adsorbing micro RNAs (miRNA). Results We used the Illumina Novaseq6,000 technology to analyze the circRNA expression profile in the endometrium of three Erhualian (EH12) and three Yorkshire (YK12) pigs on day 12 of gestation. Overall, a total of 22,108 circRNAs were identified. Of these, 4051 circRNAs were specific to EH12 and 5889 circRNAs were specific to YK12, indicating a high level of breed specificity. Further analysis showed that there were 641 significant differentially expressed circRNAs (SDEcircRNAs) in EH12 compared with YK12 (FDR

Nowadays, the extremely-low-frequency electromagnetic field (ELF-EMF) is recognized as environmental pollution. The data indicate that the ELF-EMF may affect factors related to epigenetic regulation and alter important biological processes in the uterus. The impact of the ELF-EMF on apoptosis and oxidative-stress-related genes has not been documented in porcine endometrium. This raises the question of whether the exposure to the ELF-EMF can induce apoptosis and/or oxidative stress in the endometrium of pigs during the peri-implantation period. Porcine endometrial slices (100 ± 5 mg) collected (n = 5) during the peri-implantation period were treated in vitro with ELF-EMF at a frequency of 50 Hz and flux density of 8 × 104 mG for 2 h. To determine the effect of ELF-EMF on apoptosis and oxidative stress in the endometrium, CASP3, CASP7, CIDEB, GADD45G, NOS1, NOS2, NOS3, and TP53I3 mRNA transcript were analyzed using real-time PCR, and protein abundance of CASP3, CASP7 using Western blot, and eNOS using ELISA were determined. Moreover, CASP3/7 and NOS activity was analyzed using flow cytometry and colorimetry, respectively. The decreased CASP7 and increased NOS3 mRNA transcript and protein abundance in ELF-EMF-treated endometrium were observed. Moreover, CIDEB, GADD45G, and TP53I3 mRNA transcript abundance was increased. Only p ≤ 0.05 was considered a statistically significant difference. The documented alterations indicate the potential of the ELF-EMF to affect apoptosis and generate oxidative stress in the endometrium. The insight into observed consequences documents for the first time the fact that the ELF-EMF may influence endometrial cell proliferation, angiogenesis, and/or tissue receptivity during peri-implantation.

Background: One of the most critical periods for the loss of pig embryos is the 12th day of gestation when implantation begins. Recent studies have shown that non-coding RNAs (ncRNAs) play important regulatory roles during pregnancy. Circular RNAs (circRNAs) are a kind of ubiquitously expressed ncRNAs that can directly regulate the binding proteins or regulate the expression of target genes by adsorbing micro RNAs (miRNA). Results: We used the Illumina Novaseq6,000 technology to analyze the circRNA expression profile in the endometrium of three Erhualian (EH12) and three Yorkshire (YK12) pigs on day 12 of gestation. Overall, a total of 22,108 circRNAs were identified. Of these, 4051 circRNAs were specific to EH12 and 5889 circRNAs were specific to YK12, indicating a high level of breed specificity. Further analysis showed that there were 641 significant differentially expressed circRNAs (SDEcircRNAs) in EH12 compared with YK12 (FDR < 0.05). Functional enrichment of differential circRNA host genes revealed many pathways and genes associated with reproduction and regulation of embryo development. Network analysis of circRNA-miRNA interactions further supported the idea that circRNAs act as sponges for miRNAs to regulate gene expression. The prediction of differential circRNA binding proteins further explored the potential regulatory pathways of circRNAs. Analysis of SDEcircRNAs suggested a possible reason for the difference in embryo survival between the two breeds at the peri-implantation stage. Conclusions: Together, these data suggest that circRNAs are abundantly expressed in the endometrium during the peri-implantation period in pigs and are important regulators of related genes. The results of this study will help to further understand the differences in molecular pathways between the two breeds during the critical implantation period of pregnancy, and will help to provide insight into the molecular mechanisms that contribute to the establishment of pregnancy and embryo loss in pigs. [ABSTRACT FROM AUTHOR]

Mitochondrial remodeling during the peri-implantation stage is the hallmark event essential for normal embryogenesis. Among the changes, enhanced oxidative phosphorylation is critical for supporting high energy demands of postimplantation embryos, but increases mitochondrial oxidative stress, which in turn threatens mitochondrial DNA (mtDNA) stability. However, how mitochondria protect their own histone-lacking mtDNA, during this stage remains unclear. Concurrently, the mitochondrial genome gain DNA methylation by this stage. Its spatiotemporal coincidence with enhanced mitochondrial stress led us to ask if mtDNA methylation has a role in maintaining mitochondrial genome stability. Herein, we report that mitochondrial genome undergoes de novo mtDNA methylation that can protect mtDNA against enhanced oxidative damage during the peri-implantation window. Mitochondrial genome gains extensive mtDNA methylation during transition from blastocysts to postimplantation embryos, thus establishing relatively hypermethylated mtDNA from hypomethylated state in blastocysts. Mechanistic study revealed that DNA methyltransferase 3A (DNMT3A) and DNMT3B enter mitochondria during this process and bind to mtDNA, via their unique mitochondrial targeting sequences. Importantly, loss- and gain-of-function analyses indicated that DNMT3A and DNMT3B are responsible for catalyzing de novo mtDNA methylation, in a synergistic manner. Finally, we proved, in vivo and in vitro, that increased mtDNA methylation functions to protect mitochondrial genome against mtDNA damage induced by increased mitochondrial oxidative stress. Together, we reveal mtDNA methylation dynamics and its underlying mechanism during the critical developmental window. We also provide the functional link between mitochondrial epigenetic remodeling and metabolic changes, which reveals a role for nuclearmitochondrial crosstalk in establishing mitoepigenetics and maintaining mitochondrial homeostasis. [ABSTRACT FROM AUTHOR]

Mammalian preimplantation development culminates in the formation of a blastocyst which undergoes extensive gene expression regulation to successfully implant into the maternal endometrium. Zinc-finger HIT domain-containing (ZNHIT) 1 and 2 are members of a highly conserved family, yet they have been identified as subunits of distinct complexes. Here we report that knockout of either Znhit1 or Znhit2 results in embryonic lethality during peri-implantation stages. Znhit1 and Znhit2 mutant embryos have overlapping phenotypes, including reduced proportion of SOX2-positive ICM cells, a lack of Fgf4 expression and aberrant expression of NANOG and SOX17. Furthermore, we find that the similar phenotypes are caused by distinct mechanisms. Specifically, embryos lacking ZNHIT1 likely fail to incorporate sufficient H2A.Z at the promoter region of Fgf4 and other genes involved in cell projection organization resulting in impaired invasion of trophoblast cells during implantation. In contrast, Znhit2 mutant embryos display a complete lack of nuclear EFTUD2, a key component of U5 spliceosome, indicating a global splicing deficiency. Our findings unveil the indispensable yet distinct roles of ZNHIT1 and ZNHIT2 in early mammalian embryonic development., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine what patient and embryo characteristics are correlated with the developmental potential of the peri-implantation embryo.Design: Retrospective study.Setting: Research laboratory.Patients: Six hundred fifty-one cryopreserved human blastocysts donated for research with informed patient consent.Interventions: Not applicable.Main Outcome Measures: Blastocyst attachment to fibronectin-coated plates, trophectoderm outgrowth area, epiblast cell number, total cell number, human chorionic gonadotropin secretion.Results: Patients' body mass index, age, follicle-stimulating hormone: luteinizing hormone ratio on menstrual cycle day 3, antral follicle count on menstrual cycle day 3, antimüllerian hormone level on menstrual cycle day 3, and blastocyst morphological grade were correlated with peri-implantation development outcomes. After controlling for good-quality morphological grades, blastocysts from patients of advanced maternal age developed fewer epiblast cells than blastocysts from younger patients.Conclusions: Extended embryo culture during the peri-implantation period mirrors several disparities in fertility treatment outcome that we see clinically, including those from patients with advanced maternal age, high body mass index, and low ovarian reserve and from embryos with lower-quality morphological grades. This model system may be useful by providing an alternative or more sensitive endpoint assessment in studying patient, clinical, or laboratory factors that may influence preimplantation embryo developmental potential. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world, leading to large-scale population infection. Angiotensin-converting enzyme 2 (ACE2) is the receptor of both severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, it is still controversial whether vertical transmission exists. In order to investigate the potential risk of SARS-CoV-2 vertical transmission, we explored ACE2 and TMPRSS2 (encoding transmembrane protease serine 2) expression patterns in peri-implantation embryos and the maternal–fetal interface using previously published single-cell transcriptome data. The results showed that day 6 (D6) trophectoderm (TE) cells in peri-implantation embryos, as well as syncytiotrophoblast (STB) at 8 weeks of gestation (STB_8W) and extravillous trophoblast (EVT) cells at 24 weeks of gestation (EVT_24W) in the maternal–fetal interface, strongly co-expressed ACE2 and TMPRSS2, indicating a SARS-CoV-2 infection susceptibility. The ACE2 positive-expressing cells in the three cell types mentioned above were found to share common characteristics, which were involved in autophagy and immune-related processes. ACE2 showed no gender bias in post-implantation embryos but showed a significant gender difference in D6_TE, D6 primitive endoderm (PE) cells, and ACE2 positive-expressing STBs. These findings suggest that there may be different SARS-CoV-2 infection susceptibilities of D6 embryos of different genders and during the gestation of different genders. Our results reveal potential SARS-CoV-2 infection risks during embryo transfer, peri-implantation embryo development, and gestation.

This study compared the gene expression of extraembryonic membranes (EEM) from in vitro produced (IVP) and in vivo (AI) derived pregnancies. A piece of conceptus (day 18) or chorioallantois (day 32) was used for DNA and RNA isolation and sex determination. Male and female ratios were analyzed by Chi-square. A total of three samples per sex and group (AI and IVP, days 18 and 32) were used for transcriptome analysis. Differentially expressed genes (DEGs) were determined using edgeR-robust. A false discovery rate (FDR)

Nowadays, the extremely-low-frequency electromagnetic field (ELF-EMF) is recognized as environmental pollution. The data indicate that the ELF-EMF may affect factors related to epigenetic regulation and alter important biological processes in the uterus. The impact of the ELF-EMF on apoptosis and oxidative-stress-related genes has not been documented in porcine endometrium. This raises the question of whether the exposure to the ELF-EMF can induce apoptosis and/or oxidative stress in the endometrium of pigs during the peri-implantation period. Porcine endometrial slices (100 ± 5 mg) collected ( n = 5) during the peri-implantation period were treated in vitro with ELF-EMF at a frequency of 50 Hz and flux density of 8 × 10 4 mG for 2 h. To determine the effect of ELF-EMF on apoptosis and oxidative stress in the endometrium, CASP3 , CASP7 , CIDEB , GADD45G , NOS1 , NOS2 , NOS3 , and TP53I3 mRNA transcript were analyzed using real-time PCR, and protein abundance of CASP3, CASP7 using Western blot, and eNOS using ELISA were determined. Moreover, CASP3/7 and NOS activity was analyzed using flow cytometry and colorimetry, respectively. The decreased CASP7 and increased NOS3 mRNA transcript and protein abundance in ELF-EMF-treated endometrium were observed. Moreover, CIDEB , GADD45G , and TP53I3 mRNA transcript abundance was increased. Only p ≤ 0.05 was considered a statistically significant difference. The documented alterations indicate the potential of the ELF-EMF to affect apoptosis and generate oxidative stress in the endometrium. The insight into observed consequences documents for the first time the fact that the ELF-EMF may influence endometrial cell proliferation, angiogenesis, and/or tissue receptivity during peri-implantation., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Embryos, originating from fertilized eggs, undergo continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Chromatin regulators, including transcription factors (TFs), play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was identified as crucial in initiating early cell fate decisions. However, Tfap2c transcripts persist in both the inner cell mass and trophectoderm of blastocysts, prompting inquiry into Tfap2c's function in post-lineage establishment. In this study, we delineate the dynamics of TFAP2C during the mouse peri-implantation stage and elucidate its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we propose that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, these results highlight the plasticity of the chromatin environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The peri-implantation window of mammalian development is the crucial window for primordial germ cell (PGC) specification. Whereas pre-implantation dynamics are relatively conserved between species, the implantation window marks a stage of developmental divergence between key model organisms, and thus potential variance in the cell and molecular mechanisms for PGC specification. In humans, PGC specification is very difficult to study in vivo. To address this, the combined use of human and nonhuman primate embryos, and stem cell-based embryo models are essential for determining the origin of PGCs, as are comparative analyses to the equivalent stages of mouse development. Understanding the origin of PGCs in the peri-implantation embryo is crucial not only foraccurate modeling of this essential process using stem cells, but also in determining the role of global epigenetic reprogramming upon which sex-specific differentiation into gametes relies. [ABSTRACT FROM AUTHOR]

The main objective of this study was to assess PAG2 mRNA expression in maternal blood cells at the peri-implantation period in water buffalo; moreover, we wanted to evaluate the earliest time in which PAG-2 could be detected in maternal blood. Thirty-two lactating buffaloes artificially inseminated (AI) were utilized. Blood was collected at Days 0, 14, 18, 28, 40 after AI (AI = day 0). Pregnancy was diagnosed by ultrasound at Days 28 and 40 post AI. Out of 32 buffaloes, 14 were pregnant (P group) and 18 were not pregnant (NP group). The plasma PAG-2 threshold of 1.0 ng/mL in the P group was reached at day 40 post AI. PAG2 mRNA expression differed between the P and NP groups, and was either evaluated in Peripheral Blood Mononuclear Cells (PBMC) or Polymorphonuclear Leukocytes (PMN), starting from day 14. However, both the estimated marginal means and multiple comparisons showed that PAG2 mRNA expression was higher in PMN than PBMC. In the present study, PAG-2 appeared in the blood (40 Days post AI), and an early expression of PAG2 mRNA at Day 14 post AI was also observed. Although further research is undoubtedly required, PAG2 mRNA in peripheral blood leukocytes could be using to better understand the role that PAGs play during pregnancy in buffalo. [ABSTRACT FROM AUTHOR]

Adrenomedullin (ADM) as a highly conserved peptide hormone has been reported to increase significantly in the uterine lumen during the peri-implantation period of pregnancy in pigs, but its functional roles in growth and development of porcine conceptus (embryonic/fetus and its extra-embryonic membranes) as well as underlying mechanisms remain largely unknown. Therefore, we conducted in vitro experiments using our established porcine trophectoderm cell line (pTr1) isolated from day-12 porcine conceptuses to test the hypothesis that porcine ADM stimulates cell proliferation, migration and adhesion via AKT-TSC2-MTOR cell signaling pathway in pTr1 cells. The pTr1 cells were cultured in DMEM/F12 medium with 10% fetal bovine serum (FBS), 50 U/mL penicillin, 50 µg/mL streptomycin, 0.1 mM each for nutritionally nonessential amino acids, 1 mM sodium pyruvate, 2 mM glutamine, and 4 µg/mL insulin. Opti-MEM supplied with 2.5% (vol/vol) charcoal-stripped FBS was used for siRNAmediated knockdown targeting non-treated control (siNTC) or specific genes including ADM (siADM) and its shared receptor component calcitonin-receptorlike receptor (CALCRL; siCALCRL). Cells were starved in FBS- and insulin-free medium for 24 hours before treatment. For proliferation assay, cell numbers were determined by staining with Janus-Green B after 48 h incubation. For migration assay, cells were treated with ADM after straight scratch in 6-well plates, and area of cell migration was calculated after 12 h treatment. For adhesion assay, cells were trypsinized in T-25 flasks and allowed for seeding in 96-well plates with density of 2×105 cells/0.2 mL/well, and the numbers of attached cells were determined after 12 h incubation. Western blot analyses were used to determine the expressions of target proteins at total and phosphorylated level. Porcine ADM at 10-7 M stimulated (P < 0.05) pTr1 cell proliferation, migration and adhesion by 1.4%-, 1.5%- and 1.2%-folds, respectively. These ADM-induced effects were abrogated (P < 0.05) by siADM and siCALCRL, as well as by rapamycin, the inhibitor of mechanistic target of rapamycin (MTOR). Using siRNA-mediated knockdown of CALCRL coupled with Western blot analyses, ADM signaling transduction was determined in which ADM binds to CALCRL to increase phosphorylation of MTOR, its downstream effectors (4EBP1, P70S6K, and S6), and upstream regulators (AKT and TSC2). Collectively, these results suggest that porcine ADM in histotroph act on its receptor component CALCRL to activate AKT-TSC2-MTOR, particularly MTORC1 signaling cascade, leading to elongation, migration and attachment of conceptuses. This research was supported by Agriculture and Food Research Initiative Competitive Grant no. 2022-67015-36491 from the USDA National Institute of Food and Agriculture. [ABSTRACT FROM AUTHOR]

The main objective of this study was to assess PAG2 mRNA expression in maternal blood cells at the peri-implantation period in water buffalo; moreover, we wanted to evaluate the earliest time in which PAG-2 could be detected in maternal blood. Thirty-two lactating buffaloes artificially inseminated (AI) were utilized. Blood was collected at Days 0, 14, 18, 28, 40 after AI (AI = day 0). Pregnancy was diagnosed by ultrasound at Days 28 and 40 post AI. Out of 32 buffaloes, 14 were pregnant (P group) and 18 were not pregnant (NP group). The plasma PAG-2 threshold of 1.0 ng/mL in the P group was reached at day 40 post AI. PAG2 mRNA expression differed between the P and NP groups, and was either evaluated in Peripheral Blood Mononuclear Cells (PBMC) or Polymorphonuclear Leukocytes (PMN), starting from day 14. However, both the estimated marginal means and multiple comparisons showed that PAG2 mRNA expression was higher in PMN than PBMC. In the present study, PAG-2 appeared in the blood (40 Days post AI), and an early expression of PAG2 mRNA at Day 14 post AI was also observed. Although further research is undoubtedly required, PAG2 mRNA in peripheral blood leukocytes could be using to better understand the role that PAGs play during pregnancy in buffalo.

β-catenin (CTNNB1) is integral to cell adhesion and to the canonical Wnt signaling pathway. The effects of maternal and zygotic CTNNB1 on embryogenesis have each been separately assessed, whereas the effect of its total absence has not. As the 'traditional' conditional Ctnnb1 knockout alleles give rise to truncated CTNNB1 fragments, we designed a new knockout allele incapable of CTNNB1 production. Mouse embryos lacking intact maternal/zygotic CTNNB1 from two knockout strains were examined in detail. Preimplantation embryos are formed, yet abnormalities in their size and shape were found throughout pre- and early postimplantation development. In the absence of the zona pellucida, embryos lacking CTNNB1 undergo fission and these separated blastomeres can become small trophoblastic vesicles, which in turn induce decidual reactions. Comparing the severity of this defective adhesion phenotype in embryos bearing the null allele with those carrying the 'traditional' knockout allele suggests a hypomorphic effect of the truncated CTNNB1 protein fragment, an important observation with possible impact on previous and future studies. [ABSTRACT FROM AUTHOR]

The peri-implantation period from blastula to gastrula is one of the crucial stages of human embryo and stem cell development. During development, human embryos undergo many crucial events, such as embryonic lineage differentiation and development, structural self-assembly, pluripotency state transition, cell communication between lineages, and crosstalk between the embryo and uterus. Abnormalities in these developmental events will result in implantation failure or pregnancy loss. However, because of ethical and technical limits, the developmental dynamics of human peri-implantation embryos and the underlying mechanisms of abnormal development remain in a "black box." In this review, we summarize recent progress made toward our understanding of human peri-implantation embryogenesis based on extended in vitro cultured embryos and stem cell-based embryoids. These findings lay an important foundation for understanding early life, promoting research into human stem cells and their application, and preventing and treating infertility. We also propose key scientific issues regarding peri-implantation embryogenesis and provide an outlook on future study directions. Finally, we sum up China's contribution to the field and future opportunities., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Aggressive embryo and receptive endometrium are necessary for successful implantation. On this time endometrium transformates to receptive state, which permits embryonic implantation. Studies about embryonic implantation and endometrial receptivity are always a hot spot in the field of reproductive medicine. Objective: To investigate the expression pattern of Meis1 during peri-implantation in mice endometrium. Materials and Methods: Mice for experiment were raised in SPF environment. The mice were mated with a female/male ratio of 2:1. The female mice with detected plugs were regarded as pregnant day 1 (pd1). Endometrial tissues were collected respectively on pd1, pd2, pd4, pd5 and pd6. Immunohistochemistry was used to detect the location of Meisl in mice endometrium. The expression level of mRNA and protein of Meisl were further detected using Quantitative PCR and Western blotting, respectively. Results: We found that Meis1 is located in the cytoplasm and membrane of endometrial glandual epithelium cells and the nucleus of endometrial stromal and decidual cells. Both Quantitative RT-PCR and western blotting showed that Meis1 expressed regularly in mice endometrium. Meisl mRNA expressed weakly on pd1, then significantly increased on pd4 (p=0.018), and achieved to a peak on pd5 (p=0.0012), it showed a decrease trend on pd6. Meis1 protein expressed weakly on pd1 and pd2, then significantly increased on pd4 and pd5 (p=0.0019), it showed a decrease trend on pd6 Conclusion: Meis1 is dynamically expressed in mice endometrium during peri-implantation. The time that Meisl expression reaches its peak value is coincident with the implantation window, which implied that Meis1 is closely related with embryonic implantation. [ABSTRACT FROM AUTHOR]

Embryonic mortality and intrauterine growth retardation (IUGR) are induced by exposure of rodents to xenobiotic agents during the pregastrulation period of development. We examined the time course of the effects of methyl methanesulfonate (MMS), an alkylating agent, on conceptus development in order to clarify the relative roles of the embryo and the placenta in their induction. Pregnant rats were treated orally with a single dose of MMS (200 mg/kg) in the morning of gestation day (GD) 6 (peri-implantation stage). Embryonic mortality was increased on GD12 and thereafter by MMS treatment, with newly dead embryos showing placental hypoplasia at GD12. Embryo or fetal weight was also smaller for MMS-treated dams than for control dams from GD14 to GD20. The labyrinth zone and junctional zone (JZ) of the placenta were thinner in MMS-treated rats from GD12 to GD17 and from GD12 to GD20 (except for GD17), respectively. Furthermore, MMS-treated dams showed a smaller number of glycogen cells in the JZ on GD14. In contrast, the placental glycogen concentration was higher and the expression of glucose transporter 1 in the JZ remained at GD20. These results indicate that exposure of pregnant rats to MMS at the peri-implantation stage of embryogenesis affects placental development and growth. The placental impairment induced by MMS was likely responsible for the embryonic death observed 6 days after exposure of dams to this agent as well as for the IUGR of surviving embryos or fetuses throughout the gestation period. [ABSTRACT FROM AUTHOR]

Objective: To characterize the hourly profiles of hCG secretion in blood during conceptive cycles that ended in successful pregnancy. Design: Prospective study. Setting: University fertility clinic and research laboratories. Patient(s): Healthy spontaneously ovulating women with regular menses, no history of infertility, and either no male partner or an azospermic partner. Intervention(s): Frequent blood samples were collected daily from 11 spontaneously ovulating women during 11 cycles of artifical insemination with donor semen. The concentrations of hCG, LH, and FSH were measured in the blood by immunoassay. Main Outcome Measure(s): The concentration of hCG in the frequent blood samples and the rate that the concentration of hCG changed during the period of frequent sampling. Result(s): For the conceptive cycles resulting in successful pregnancies analyzed, hourly hCG concentrations were observed to increase in a consistent nonpulsatile manner. Conclusion(s): These data provide the first characterization of the hourly secretion profile of hCG in early pregnancy as well as provide further evidence that individual daily blood samples are sufficient for the accurate assessment of pregnancy. [Copyright &y& Elsevier]

Objective To investigate changes in utero-ovarian blood flow during the peri-implantation period and their significance in successful embryo implantation. Methods A prospective longitudinal study was conducted in 317 women undergoing in-vitro fertilization-embryo transfer (IVF-ET) treatment. All of them had at least one good-quality embryo for transfer on the second or third day after oocyte retrieval. Measurement of endometrial thickness and color flow imaging with pulsed waveform analysis of uterine and ovarian arteries were performed before ET and 5–6 days after ET. Results There were no significant differences in the age of patients, duration of infertility or number of embryos transferred between women who became pregnant (n = 91) and those who did not (n = 226). There was no difference in mean endometrial thickness between the two groups before ET, while a thicker endometrium was found in women who had conceived compared with those who had not 5–6 days after ET (P = 0.02). Mean uterine arterial resistance index (RI) and pulsatility index (PI) values were significantly lower in the pregnant than in the non-pregnant group before ET (P = 0.04 and P = 0.003, respectively), but no significant differences were found between the two groups 5–6 days after ET. In contrast, the mean ovarian arterial RI and P1 values were similar between the two groups before ET, yet the pregnant group showed significantly lower RI and PI values compared with the non-pregnant group 5–6 days after ET (P = 0.002 and P = 0.01, respectively). A significantly higher peak systolic velocity (PSV) of intraovarian vessels was also noted in the pregnant group 5–6 days after ET. [ABSTRACT FROM AUTHOR]

Human development has been studied for over a century, but the molecular mechanisms underlying human embryogenesis remain largely unknown due to technical difficulties and ethical issues. Accordingly, mice have been used as a model for mammalian development and studied extensively to infer human biology based on the conservation of fundamental processes between the two species. As research has progressed, however, species-specific differences in characteristics between rodents and primates have become apparent. Non-human primates (NHPs) have also been used for biomedical research, and are now attracting attention as a model for human development. Here, we summarize primate species from the evolutionary and genomic points of view. Then we review the current issues and progress in gene modification technology for NHPs. Finally, we discuss recent studies on the early embryogenesis of primates and future perspectives., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world, leading to large-scale population infection. Angiotensin-converting enzyme 2 (ACE2) is the receptor of both severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, it is still controversial whether vertical transmission exists. In order to investigate the potential risk of SARS-CoV-2 vertical transmission, we explored ACE2 and TMPRSS2 (encoding transmembrane protease serine 2) expression patterns in peri-implantation embryos and the maternal-fetal interface using previously published single-cell transcriptome data. The results showed that day 6 (D6) trophectoderm (TE) cells in peri-implantation embryos, as well as syncytiotrophoblast (STB) at 8 weeks of gestation (STB&#95;8W) and extravillous trophoblast (EVT) cells at 24 weeks of gestation (EVT&#95;24W) in the maternal-fetal interface, strongly co-expressed ACE2 and TMPRSS2 , indicating a SARS-CoV-2 infection susceptibility. The ACE2 positive-expressing cells in the three cell types mentioned above were found to share common characteristics, which were involved in autophagy and immune-related processes. ACE2 showed no gender bias in post-implantation embryos but showed a significant gender difference in D6&#95;TE, D6 primitive endoderm (PE) cells, and ACE2 positive-expressing STBs. These findings suggest that there may be different SARS-CoV-2 infection susceptibilities of D6 embryos of different genders and during the gestation of different genders. Our results reveal potential SARS-CoV-2 infection risks during embryo transfer, peri-implantation embryo development, and gestation., (© 2020 THE AUTHORS.)

Fibroblast growth factor 2 (FGF2) is a mitogen that induces proliferation, differentiation, and migration of cells, as well as angiogenesis and carcinogenesis via autocrine or paracrine actions. Fibroblast growth factor 2 expression is abundant in porcine conceptuses and endometrium during the estrous cycle and peri-implantation period of pregnancy. However, its intracellular actions in uterine epithelial cells have not been reported. The results of this study indicated abundant expression of FGFR1 and FGFR2 predominantly in uterine luminal and glandular epithelia during early pregnancy and that their expression decreased with increasing parity of the sows. Treatment of porcine uterine luminal epithelial (pLE) cells with FGF2 increased proliferation and DNA replication based on increases in proliferating cell nuclear antigen (PCNA) and initiation of G1/S phase progression. In addition, FGF2 increases phosphorylation of AKT, P70S6K, S6, ERK1/2, JNK, P38, and P90RSK in a time-dependent manner, and increases in their expression was suppressed by Wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), U0126 (an ERK1/2 inhibitor), SP600125 (a JNK inhibitor), and SB203580 (a P38 inhibitor) based on western blot analyses. Also, the abundance of cytoplasmic p-AKT protein was decreased by Wortmannin and U0126, and p-ERK1/2 protein was reduced only by U0126. Furthermore, inhibition of each signal transduction protein reduced the ability of FGF2 to stimulate proliferation and migration of pLE cells. Collectively, these results indicate that activation of FGFR1 and FGFR2 by uterine- and endometrial-derived FGF2 stimulates PI3K/AKT and mitogen-activated protein kinase pathways for development of the porcine uterus and improvement of litter size., (© The Authors 2016. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.)

Background: Aggressive embryo and receptive endometrium are necessary for successful implantation. On this time endometrium transformates to receptive state, which permits embryonic implantation. Studies about embryonic implantation and endometrial receptivity are always a hot spot in the field of reproductive medicine., Objective: To investigate the expression pattern of Meis1 during peri-implantation in mice endometrium., Materials and Methods: Mice for experiment were raised in SPF environment. The mice were mated with a female/male ratio of 2:1. The female mice with detected plugs were regarded as pregnant day 1 (pd1). Endometrial tissues were collected respectively on pd1, pd2, pd4, pd5 and pd6. Immunohistochemistry was used to detect the location of Meis1 in mice endometrium. The expression level of mRNA and protein of Meis1 were further detected using Quantitative PCR and Western blotting, respectively., Results: We found that Meis1 is located in the cytoplasm and membrane of endometrial glandual epithelium cells and the nucleus of endometrial stromal and decidual cells. Both Quantitative RT-PCR and western blotting showed that Meis1 expressed regularly in mice endometrium. Meis1 mRNA expressed weakly on pd1, then significantly increased on pd4 (p=0.018), and achieved to a peak on pd5 (p=0.0012), it showed a decrease trend on pd6. Meis1 protein expressed weakly on pd1 and pd2, then significantly increased on pd4 and pd5 (p=0.0019), it showed a decrease trend on pd6 CONCLUSION: Meis1 is dynamically expressed in mice endometrium during peri-implantation. The time that Meis1 expression reaches its peak value is coincident with the implantation window, which implied that Meis1 is closely related with embryonic implantation.