Biology subjects

Modi, D.

Publications and source records attributed to Modi, D..

2 recordsLinked to original sources

bioRxiv2019

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

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.

developmental biology↗

bioRxiv2019

Ontogeny and expression profiles of steroid hormone receptors in a mouse model of endometriosis

Endometriosis is a chronic incurable disorder of unknown etiology affecting a large proportion of women in reproductive age. In order to understand the pathogenesis and preclinical testing of drugs,animal models that recapitulate the key features of the disorder are highly desirous. Herein, we describe the ontogeny of the ectopic endometrial lesion in a mouse model where uterine tissue was ligated to the intestinal mesentery and the animals were followed up from day 5 to day 60 post-surgery. Out of 60 animals that underwent surgery, 58 developed endometriosis using this strategy. Most lesions were pale, fluid filled while red lesions were seen in ~10% of animals. Histologically, in most animals there was one large cystic gland with well differentiated epithelium, in 13% of animals there was mixed phenotype (well and poorly differentiated). There was extensive stromal compaction and increased number of macrophages in ectopic lesions. During the course of endometriosis, there was an increase in number of PCNA positive epithelial and stromal cells. The epithelial cells at all the time point were cytokeratin positive and the stroma was vimentin positive. However, at day 30 and 60, the stromal cells were also cytokeratin positive. The mRNA levels of estrogen receptors Esr1 and Gper1 were reduced while those of Esr2 were elevated as compared to normal endometrium, the levels of progesterone receptor (Pgr) were found to be downregulated in ectopic lesions as compared to control. However, these differences were not statistically significant due to high biological variability. Low abundance of Cyp19a1 transcripts (aromatase gene) were only detected in the ectopic endometrium. Immunohistochemically, the expression of ER and ER{beta} was significantly reduced only in stromal cells; the epithelial cell staining was maintained. GPER1 and PR immunoreactivity was significantly low in both epithelial and stromal cells. The immunostaining of all the steroid receptors was highly heterogeneous in the ectopic tissues with some areas of sections had stained intensely while others had negligible staining. We propose that temporal and spatial difference in the expression of steroid hormone receptors during the course of endometriosis development coupled with micro-heterogeneity may alter the effectiveness of steroid hormone analogues resulting in variable outcomes and often failure of therapy.

pathology↗