bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/629956

No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes

G, R.·Veerasigamani, G.·Ashraf, M. C.·Singh, S.·Laheri, S.·Modi, D.
View original source ↗Export metadata ↓

Abstract

Study questionCan mitochondrial DNA (mtDNA) levels in trophectodermal cells of the blastocyst predict the blastocyst quality, ploidy status, implantation rate and clinical outcomes?\n\nSummary answermtDNA levels in trophectodermal cells of the blastocyst do not associate with the blastocyst quality, ploidy status, implantation potential and clinical outcomes, but can differentiate between aneuploid and euploid blastocysts.\n\nWhat we already knowmtDNA levels in the trophectodermal cells have been suggested to be associated with blastocyst morphology, ploidy and implantation rates, and has been proposed as biomarker to access blastocyst quality and predict clinical outcomes. However, discrepancies exist if mtDNA levels could serve as a marker for the same.\n\nStudy design and durationRetrospective analysis of mtDNA levels in trophectodermal cells obtained from blastocysts undergoing preimplantation genetic testing for aneuploidy (PGT-A) at Craft Hospital & Research Center, Kerala from January 2016-July 2017.\n\nParticipants/materials and methodsStudy included data from 287 blastocyst from (61) couples who underwent PGT-A using next generation sequencing (NGS). Levels of mtDNA in trophectodermal cells of the blastocyst were estimated by the NGS. Comparison of mtDNA levels with maternal age, blastocyst morphology, ploidy status, implantation rates, miscarriage rates and live birth rate was done.\n\nMain resultsThe levels of mtDNA in the trophectoderm of the blastocyst did not correlate with maternal age. There was no significant difference in the mtDNA levels between grade 1 and grade 2 blastocyst. Euploid blastocyst had significantly lower amounts of mtDNA levels in trophectodermal cells of the blastocyst were compared to aneuploid blastocyst. No significant differences were seen between mtDNA levels and implanting and non-implanting blastocysts or those resulted into miscarriage or live birth.\n\nLimitationsThe study is limited by a small sample size and hence type II error cannot be ruled out.\n\nWider ImplicationsThe study does not support the potential use of mtDNA levels in the trophectodermal cells as biomarker for blastocyst quality and predicting clinical outcomes needs.\n\nStudy funding/competing interest(s)There is no external funding for the study. There is no conflict of interest.

Explore related subjects

developmental biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

G, R., Veerasigamani, G., Ashraf, M. C., Singh, S., Laheri, S., Modi, D.. 2019-05-07. No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes. https://doi.org/10.1101/629956

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Prenatal THC exposure alters metabolic gene expression and KEAP1 regulation in the mouse placental labyrinth

Introduction: Prenatal cannabinoid exposure may influence fetal development through changes in placental biology, yet its effects on metabolic gene regulation remain poorly understood. We examined the effects of {Delta}9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on the mouse placental labyrinth zone. Methods: Pregnant C57BL/6JRj mice received THC (5 mg/kg), CBD (5 mg/kg), or vehicle daily by intraperitoneal injection from gestational day 5 to 17.5. Targeted NanoString profiling and pathway analysis were combined with RT-qPCR and protein measurements. Results: THC exposure reduced glutaminase (Gls), Kelch-like ECH-associated protein 1 (Keap1), and FMS-like tyrosine kinase 3 (Flt3) expression (false discovery rate = 0.0904 for each). Pathway analysis identified transcriptional changes in the nine-gene arginine-metabolism set (false discovery rate = 0.0527). No genes or pathways met the significance criteria following CBD exposure. RT-qPCR confirmed lower Keap1 expression with sexes pooled and identified lower Gls and Flt3 expression in male samples. KEAP1 protein abundance increased despite lower Keap1 mRNA, while nuclear factor erythroid 2-related factor 2 localization and heme oxygenase 1 (Hmox1) expression showed no significant differences. Discussion: These findings identify amino acid metabolic gene expression and KEAP1 regulation as complementary components of the placental response to prenatal THC exposure, connecting transcriptional changes with protein regulation within the placental exchange region.

developmental biology↗
bioRxiv2026

Mutually Repressive Transcription Factors Drive Intestinal Maturation for Weaning

In mammals, rapid neonatal growth depends on specialized intestinal enterocytes that absorb nutrients from milk. These cells exhibit distinct functions, morphologies, and gene expression programs that support neonatal nutrition before transitioning to an adult state at weaning. However, the transcriptional mechanisms that establish neonatal enterocyte identity and coordinate their maturation remain poorly understood. Here we show that the transcription factors BLIMP1 and CASZ1 form a central switch in the timing of enterocyte maturation. While BLIMP1 marks and promotes neonatal enterocytes, CASZ1 is expressed in adult enterocytes and is required for the proper timing of their emergence. Genetic analysis indicates that these neonatal and adult factors are mutually repressive, forming a genetic switch underlying weaning. This regulatory mechanism also controls glucocorticoid-induced maturation, a process relevant to both normal weaning and the clinical use of corticosteroids to promote epithelial maturation in preterm infants. We show that corticosteroids act directly on the intestinal epithelium and require CASZ1 to induce maturation. Together, these findings reveal a transcriptional mechanism that coordinates intestinal epithelial identity with the changing nutritional demands of early life and mediates the response to maturation-promoting hormones.

developmental biology↗
bioRxiv2026

Functional Data Clustering of Filopodia Dynamics

Notch signaling plays a significant role in tissue patterning. During patterning of the fruit fly dorsal thorax peripheral nervous system, basal filopodia extend the spatial range of cell-cell communication, yet it is still unclear how Notch is activated in long range signaling via filopodia interaction. Filopodia undergo dynamic length changes during their lifetime, which could supply the mechanical pulling force required for notch activation. However, their dynamics are often characterized using individual scalar values such as maximum length and extension rate which could obscure more intricate dynamics. Our hypothesis is that signaling filopodia exhibit distinct and recurrent temporal patterns which can be identified by a consideration of their complete lifetime trajectories. Our work analyzes 60 filopodia trajectories at the basal surface of the fly dorsal thorax during patterning. Length profiles were smoothed using cubic B-splines and clustered by first reducing them to their dominant functional principal component followed by the application of various clustering algorithms. We found that 94.29% of the overall trajectory variation is explained by the first four functional principal components which account for variations in maximal length, extension and retraction rate, duration of stationary phase and length fluctuation frequency. Five recurrent temporal profiles (dynamic extension modes) with varying trajectory shapes and physical attributes, were identified using trimmed K-means. These findings demonstrate that whereas the major source of structural variation in filopodia profiles remains the length, extension rate and retraction rate, nontrivial combinations of these create distinct dynamic modes of extension which provide new insight into their length profiles. Our work thus offers a quantitative framework for future research connecting filopodia dynamic extension modes to productive Notch activation.

developmental biology↗