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PubMed2026

Cumulus cells enhance oocyte genomic quality control by promoting DNA damage-induced meiotic arrest.

Cumulus cells are known to maintain oocyte arrest at prophase I through gap junction-mediated cAMP signalling, but their role after meiotic resumption remains unclear. Here, we show that cumulus cells enhance oocyte genomic quality control by sensitizing mouse oocytes to DNA damage-induced meiotic arrest. Time-lapse imaging of SiR-tubulin-labelled spindles revealed that oocytes from cumulus-oocyte complexes (COCs) matured faster than denuded oocytes (DOs). Upon mild DNA damage induced by low-dose etoposide, COC oocytes arrested at metaphase I, whereas DOs completed maturation despite similar levels of DNA lesions. This arrest required spindle assembly checkpoint (SAC) activity, as reversine rescued polar body extrusion and BubR1 and Mad2 were elevated in COCs but not DOs. Disruption of gap junctions or inhibition of mTOR signalling abolished the checkpoint response. Notably, cumulus cells did not enhance oocyte response to minor spindle perturbations. These findings reveal a previously unrecognized role of cumulus cells in mediating DNA damage-induced SAC activation, providing post-GVBD genomic surveillance beyond prophase I arrest.

Animals↗

PubMed2026

IVM rescue: Effect of growth hormone supplementation combined to autologous cumulus co-culture on GV oocyte maturation and competency.

OBJECTIVE: IVM rescue is based on the in vitro maturation of mainly Germinal Vesicle (GV) oocytes collected from stimulated cycles. The objective was to investigate the effects of growth hormone (GH) and autologous cumulus cells co culture (CC) on oocyte meiosis resumption and maturation after 32 h post cumulus denudation, in order to obtain additional embryos for the couple as a rescue system to increase the changes of cumulative pregnancy. MATERIAL AND METHODS: Our study concerned 300 patients who underwent ICSI cycles, during which a total of 1940 cumulus-complex-oocytes were retrieved, giving 1260 metaphase II stage (MII), 200 at the metaphase I stage, and 480 at the Germinal Vesicle (GV) stage. Mature oocytes were microinjected on the same day of retrieval. Immature GV oocytes were divided into four groups, with the first undergoing in vitro maturation (IVM) without cumulus cells (group 1) and the second undergoing IVM with CC (group 2), the third undergoing IVM without CC and with GH (group 3), the fourth undergoing IVM with CC and with GH (group 4). After 32 h of IVM, the matured oocytes, underwent microinjection, followed by embryonic development monitoring. RESULTS: When comparing the IVM outcomes, we observed a significant increase in oocyte maturation, fertilization rates and the percentage of 8-cell embryos on day 3 across the different study groups (p < 0.001) (Figs. 2-5). Furthermore, all study groups (1-4) exhibited notably blastulation rates, with group 3 demonstrating the most promising clinical outcomes. A preliminary pregnancy rate of approximately 20% was recorded in group 3, suggesting a potential improvement in the developmental competence of oocytes matured under specific conditions. CONCLUSION: The IVM rescue of germinal vesicle oocyte could serve as an additional strategy to increase the chance getting extra embryos to patients. Autologous cumulus cells co-culture combined to GH supplementation to IVM media, appear to play a crucial role to enhance successful meiosis resumption, oocyte maturation and competency to support embryos development when the injected spermatozoa is not carrier of severe genome and epigenomic decays.

Humans↗

PubMed2026

Limitations of serial cloning in mammals: unresolved donor-cell genomic integrity challenges broad claims of cloning limits.

Wakayama et al. describe an extraordinary 20-year serial cloning study in mice, concluding that serial cloning in mammals is ultimately limited by the accumulation of genetic anomalies. However, their whole-genome sequencing (WGS) analysis characterized selected cloned animals but did not include matched genomic profiling of the corresponding cumulus cell (CC)-donor mice, the source CC populations, or developmental stages. Because each reconstructed embryo originated from a single CC nucleus and re-cloned animals were used to advance the lineage, pre-existing somatic variation could have entered the lineage and subsequently been propagated. Consequently, variants detected in later generations cannot be assigned definitively to pre-existing donor-cell mosaicism, donor-cell handling, somatic cell nuclear transfer manipulation, or early embryogenesis. Thus, the observed decline cannot be attributed exclusively to genetic lesions arising during repeated cloning, but the unresolved genomic status of the lineage-founding donor cells remains a plausible but unproven contributor. The study therefore demonstrates the transmission and propagation of genetic lesions through serial cloning more directly than it establishes that all initiating lesions arose because of repeated cloning. Paired genomic profiling of donor-cell populations, embryos, and offspring would help resolve the origins of accumulated genetic lesions and determine whether donor-cell screening could extend serial cloning.

Animals↗

PubMed2026

IL17 signaling promotes oocyte developmental competence acquisition during maturation.

BACKGROUND: Defects in the acquisition of oocyte developmental competence during the maturation process causes subfertility or infertility in animals and humans. Understanding the regulatory mechanisms of oocyte maturation is essential for reproductive biology and medicine. Follicular fluid (FF) is an important microenvironment governing oocyte maturation. METHODS: A tandem mass tags (TMT)-based comparative FF proteomic analysis was employed to identify FF proteins that are potentially crucial for oocyte maturation. A very large number of pig and mouse oocytes (approximately 20,000) and embryos (over 13,000, including somatic cell nuclear transfer, parthenogenetic activation, and in vitro fertilization embryos) were used to investigate the effects of identified FF proteins on in vitro oocyte maturation and subsequent in vitro and in vivo embryo development. RNA sequencing, quantitative PCR, enzyme-linked immunosorbent assays, and immunofluorescence were used to study the expression patterns and action mechanisms of identified FF proteins in oocytes. In addition, intra-oocyte levels of glutathione and reactive oxygen species were measured to assess redox homeostasis. RESULTS: Interleukin 17D (IL17D) was identified as an important FF protein and it is significantly upregulated in porcine FF during oocyte maturation. IL17D promotes oocyte maturation by enhancing bidirectional communication between oocytes and cumulus cells, via upregulating CX43 expression and transzonal projections, which helps to maintain oocyte redox homeostasis and nuclear-cytoplasmic synchrony. IL17D treatment of oocytes enhances subsequent in vitro and in vivo full-term embryo development by modulating lipid metabolism and histone modification reprogramming. IL17D exerts its function via activating IL17 signaling through binding to CD93. Two other IL17 family members, IL17A and IL17F, also enhance oocyte maturation quality. IL17D displays a conserved expression pattern and function in pig and mouse oocytes. CONCLUSIONS: This study reveals the critical roles of IL17D in regulating oocyte developmental competence acquisition during maturation by activating IL17 signaling. The findings provide valuable insights into the molecular mechanisms underlining oocyte developmental potential acquisition and may help to develop methods for efficient production of oocytes for assisted reproduction.

Animals↗