bims-mamemb 2026-08-30 papers

Reprod Biomed Online. 2026 May 02. pii: S1472-6483(26)00286-5. [Epub ahead of print]53(5): 105745

Do blastocysts which form on day 4 have an altered pregnancy potential? A narrative review.

Mollie McGrane-Ewen, Rachael C Gregoire, Roger G Sturmey, Daniel R Brison, Peter T Ruane.

The clinical pregnancy rate for assisted reproductive technology (ART) has remained static for several years. Although the reasons for this are multifactorial, reliable selection of the single optimal embryo for transfer remains a challenge. Embryo selection currently relies on visual assessment, with judgements based on cellular morphology and timing of developmental milestones. Accepted ART practice considers that embryos should reach blastocyst stage on day 5 post oocyte insemination, and this is assumed to be the optimal day on which to utilize the embryo. However, the advent of time-lapse imaging has revealed a variable frequency of blastocyst formation, ranging from day 4 to day 7. Despite current practice not involving routine assessment on day 4, emerging evidence suggests that embryos which reach blastocyst stage and are utilized on day 4 may have an improved chance of pregnancy. Reducing time in vitro could also have benefits for ongoing pregnancy and offspring health. This review provides a clinical perspective on the relationship between the day of blastocyst formation and pregnancy outcomes. Reflecting on this evidence will allow clinical professionals to consider both monitoring and utilizing blastocysts on day 4 in order to improve pregnancy success outcomes after ART.

Keywords: Assisted reproduction; Embryo; Frozen embryo transfer; Metabolism

DOI: https://doi.org/10.1016/j.rbmo.2026.105745

Int J Mol Sci. 2026 Aug 08. pii: 7115. [Epub ahead of print]27(16):

Altered Embryonic SIRT6 and SIRT7 Expression Is Associated with Impaired Developmental Competence and Oocyte-Dependent Embryo Quality in Embryos Derived from Subfertile Males.

Alicja Kowalczyk, Mercedes Camiña García, José Ángel Hernández Malagón, Jose Pedro Araujo, Ivona Žura Žaja, Marko Pećin, Dražen Đuričić, Elżbieta Gałęska, Zbigniew Dobrzański, Marko Samardžija.

Paternal contributions to preimplantation embryo development are increasingly recognized as an important component of reproductive success, but the associations between male reproductive phenotype, early embryonic competence, and embryo molecular characteristics remain insufficiently defined. Using bovine in vitro embryo production as a translational large-mammalian model, this study evaluated whether paternal reproductive phenotype and oocyte origin were associated with embryo developmental performance and embryonic sirtuin expression. Oocytes obtained from mature cows or heifers were fertilized with semen from bulls differing in reproductive status, including bulls characterized by libido disturbances and irregular semen collection. Fertilization, cleavage, blastocyst formation, and hatching were assessed, while embryonic SIRT2, SIRT3, SIRT6, and SIRT7 expression was quantified by immunofluorescence. Early developmental endpoints were relatively preserved, whereas differences were more evident at later stages of preimplantation development. Cow-derived oocytes were associated with higher hatching rates than heifer-derived oocytes. Embryos generated using semen from bulls with an impaired reproductive phenotype showed lower developmental competence and lower SIRT6 and SIRT7 expression. SIRT6 expression showed the strongest positive correlation with hatching, and positive correlations were also observed among the analyzed sirtuins. These findings indicate that paternal reproductive phenotype and oocyte origin are associated with bovine embryo developmental competence and embryonic sirtuin profiles. Embryonic SIRT6 and SIRT7 expression may represent candidate molecular indicators of embryo competence; however, causal relationships cannot be inferred from the present study design.

Keywords: animal model; embryonic developmental competence; embryos; oocyte source; paternal effects; sirtuins

DOI: https://doi.org/10.3390/ijms27167115

Taiwan J Obstet Gynecol. 2026 Sep;pii: S1028-4559(26)00217-2. [Epub ahead of print]65(5): 918-925

An innovative non-pump gravity-driven dynamic microfluidic chip improves mouse embryo development.

Yao-Yuan Hsieh, Tsung-Tao Huang, Song-Po Pan, Jen-Hsiang Hsieh, Chi-Chen Chang, Yen-Pei Lu, Yu-Hsuan Wang, Tzu-Chieh Kao.

OBJECTIVE: Various microfluidic techniques are currently used in assisted reproductive technology. In this study, we designed an innovative nonpump microfluidic culture platform to enhance in vitro embryo culture. We evaluated its feasibility and compared its performance with that of traditional microdrop culture systems.
MATERIALS AND METHODS: We developed microfluidic chips through a series of procedures, including fabrication of an SU-8 master mold, casting of polydimethylsiloxane (PDMS) on the mold, and integration of the microfluidic device. Mouse embryos were randomly assigned to three groups: (1) a traditional static drop group, (2) static microfluidic controls, and (3) a dynamic microfluid chip group. A gravity platform with a 15° tilt angle was used to drive the culture medium through the microchannels. The cytotoxicity of the chip materials was examined using the MTT assay, and embryo development was compared among the groups.
RESULTS: MTT assay results confirmed the nontoxicity of the PDMS chip materials. The proportions of two-cell embryos that developed to the 4-8-cell, morula, and early blastocyst stages were comparable among the three groups. By contrast, embryos cultured in the dynamic microfluidic chip exhibited higher rates of development to the expanding and hatching blastocyst stages. Specifically, the percentages of embryos reaching the 4-8-cell, morula, early blastocyst, expanding blastocyst, and hatching blastocyst stages were 92.4%, 85.4%, 71.2%, 52.5%, and 45.7%, respectively, in the traditional static drop group; 93.5%, 84.5%, 69.2%, 52.2%, and 45.7%, respectively, in the static microfluidic group; and 93.8%, 86.5%, 74.5%, 67.2%, and 60.4% in the dynamic microfluidic group, respectively.
CONCLUSION: The combined microfluidic and nonpump tilting culture system provides dynamic stimulation and automatic waste removal, which are not achievable with traditional static culture systems. The use of gravity instead of a motor-driven system enhances convenience and feasibility, improving the quality of in vitro embryo culture.

Keywords: Culture chip; Microchannel; Microfluidics; PDMS; Polydimethylsiloxane

DOI: https://doi.org/10.1016/j.tjog.2025.02.009

Reproduction. 2026 Aug 26. pii: xaag105. [Epub ahead of print]

Beneficial effects of melatonin on mouse preimplantation embryo development and implantation potential: Possible involvement of clathrin-mediated endocytosis.

Yue Li, Zhiqi Wang.

Melatonin is a pleiotropic hormone with essential roles in mammalian reproduction. Our previous study demonstrated that melatonin promotes human oocyte maturation and early embryo development through enhancement of clathrin-mediated endocytosis (CME). In the present study, we investigated whether a similar melatonin-associated regulatory relationship is also observed during mouse preimplantation embryo development and implantation. Following concentration optimization, mouse zygotes were cultured with 10-9 M melatonin, 20 μM dynasore (a pharmacological inhibitor of dynamin-dependent endocytosis), or their combination. Melatonin supplementation significantly increased blastocyst formation and subsequent implantation potential. Conversely, dynasore treatment reduced blastocyst developmental progression and markedly impaired implantation potential. Importantly, melatonin supplementation significantly improved the implantation potential of dynasore-treated embryos. These findings demonstrate that melatonin promotes mouse preimplantation embryo development and implantation potential, and suggest that CME-related processes may contribute to these beneficial effects. Together with our previous findings in human oocytes and early embryos, the present study provides evidence supporting a shared melatonin-associated regulatory relationship between human and mouse reproductive systems. Given that suboptimal embryo implantation remains a major limitation in assisted reproductive technology, our findings suggest that melatonin supplementation warrants further investigation as a potential strategy for optimizing in vitro embryo culture conditions and improving implantation outcomes.

Keywords: Clathrin-mediated endocytosis; Embryo development and implantation; Melatonin; Mouse

DOI: https://doi.org/10.1093/reprod/xaag105

Nat Cell Biol. 2026 Aug 25.

Elevated contractility drives implantation failure in mouse embryos from aged females.

Kate E Cavanaugh, M J Franco-Oñate, Nicole Horsley, Dilan Gokyer, Tomiris Atazhanova, Diana J Laird, Patrick W Oakes, Joan K Riley, Francesca E Duncan, MaryEllen Pavone, Matteo Molé, Ricard Alert, Orion D Weiner.

Women in their mid-30s experience a marked decline in fertility. The origin of these fertility defects resides in the implantation capacity of the embryo itself, but the mechanistic basis of this impairment is not well understood. Here we identify a core mechanical defect in embryos from aged females that impairs their implantation competence. Using mouse models, we find that reproductive ageing drives excessive contractility in the trophectoderm, the outer epithelial lineage that enables implantation. This hypercontractility increases blastocyst tissue surface tension and viscosity, which hinders spreading during implantation. Elevated contractility is both necessary and sufficient for age-associated implantation failure. We identify non-invasive imaging signatures that infer embryo mechanics and predict implantation success for embryos of both young and aged females. Analyses of human embryos and in vitro fertilization clinical datasets reveal conserved age-associated mechanical alterations that correlate with implantation potential. Our work implicates embryo mechanics as a key regulator of reproductive longevity.

DOI: https://doi.org/10.1038/s41556-026-02052-1