Comparative study of difference in anatomy & histopathology of placenta & umbilical cord in natural pregnancy vs. IVF pregnancy & it's impact on fetal & maternal outcome.

AIM AND OBJECTIVES: Comparison of naturally conceived pregnancy with IVFET pregnancy for feto-maternal outcome and morphology and histopathology of placenta & umbilical cord. METHODS: 100 pregnant women were divided into 2 subsets of spontaneous pregnancy group (n = 50) and the IVFET pregnancy group (n = 50).The two groups were compared for Maternal age, parity, maternal weight gain, prepregnancy maternal BMI, gestational age, birth weight of baby, placental weight, placenta and umbilical cord cross sections, insertion site of the umbilical cord, and length of the umbilical cord. INCLUSION CRITERIA: Patients registered at ANC OPD/ART centre of our institute and subsequently reporting to maternity ward/ labor room for delivery at our centre. EXCLUSION CRITERIA: The pregnancies conceived after ART outside our institute, multifetal pregnancies. Study duration: 01 year Results: Our study revealed that spontaneous pregnancy group had less antenatal co-morbidities with more number of term vaginal deliveries and less intrapartum and neonatal complications compared to IVFET pregnancy women (p < 0.05). CONCLUSIONS: Assisted reproductive technologies have an impact on placental growth and function in pregnancy. The occurrence of placental abnormalities were the most significant and pertinent finding in the IVF-ET placentas. On histopathological examination maternal vascular malperfusion and concomitant anomalies of the umbilical cord were most noticeable findings.

Interplay between symmetric arginine dimethylation and ubiquitylation regulates TDP1 proteostasis for the repair of topoisomerase I-DNA adducts.

Tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond between a DNA 3' end and a tyrosyl moiety and is implicated in the repair of trapped topoisomerase I (Top1)-DNA covalent complexes (Top1cc). Protein arginine methyltransferase 5 (PRMT5) catalyzes arginine methylation of TDP1 at the residues R361 and R586. Here, we establish mechanistic crosstalk between TDP1 arginine methylation and ubiquitylation, which is critical for TDP1 homeostasis and cellular responses to Top1 poisons. We show that R586 methylation promotes TDP1 ubiquitylation, which facilitates ubiquitin/proteasome-dependent TDP1 turnover by impeding the binding of UCHL3 (deubiquitylase enzyme) with TDP1. TDP1-R586 also promotes TDP1-XRCC1 binding and XRCC1 foci formation at Top1cc-damage sites. Intriguingly, R361 methylation enhances the 3'-phosphodiesterase activity of TDP1 in real-time fluorescence-based cleavage assays, and this was rationalized using structural modeling. Together, our findings establish arginine methylation as a co-regulator of TDP1 proteostasis and activity, which modulates the repair of trapped Top1cc.

Post-translational regulation of Tyrosyl-DNA phosphodiesterase (TDP1 and TDP2) for the repair of the trapped topoisomerase-DNA covalent complex.

DNA topoisomerases are essential enzymes that regulate DNA topology, the transmission of genetic materials, and gene expressions both in the nucleus and mitochondria. Trapped topoisomerases (Top1 and Top2) in covalent complexes with DNA (Topoisomerase cleavage complexes; Topcc) are detrimental DNA lesions that perturb active genome integrity and trigger cell death. Comprehensive research on the recently discovered enzymes TDP1 and TDP2 exemplify their spectacular role in repairing trapped Topcc as well as in a myriad of diverse DNA lesions. Posttranslational modifications (PTMs), play critical roles in regulating the optimal function of the DNA Damage Response (DDR) proteins. This review summarizes the mechanistic aspects of DNA damage induced by trapped Topcc during transcription and their role in human diseases. We have also highlighted the pivotal role of PTMs in fine-tuning the intricate and multilayered regulatory processes of TDP1 and TDP2 molecular networks for the repair of trapped Topcc.