An observational study cum research was conducted on Effectiveness of Glycemic Control in PCO pregnancy outcome as part of clinical audit.
We are collaborate with Institutions and Organizations to carry out research in the field of Human Reproductive Medicine and Assisted Reproductive Techniques. The research projects are placed and permitted by the In-House Institutional Ethics Committee before starting the scientific work.
Research work in Collaboration with Rajiv Gandhi Center for Biotechnology, Poojapura, Trivandrum : PUBLISHED ARTICLES
Authors-Meera Balakrishna Menon Krishna, Madavan Vasudevan,Sathy Madhavan Pillai and Malini Laloraya.
Earlier studies have exposed the miRNAs and mRNAs involved in Polycystic Ovarian Syndrome (PCOS), but little is known about their regulatory networks. To address this issue we have applied a comprehensive miRNA, mRNA profiling approach in peripheral blood of PCOS patients and identified 30 differential miRNAs and 3310 differential transcripts.A robust computational framework was created to integrate matched miRNA and mRNA expression profiles in PCOS using feed-forward loops.The network consisted of differential miRNAs,transcription factors(TFs), and their common predicted target genes.The key network consisted of 14 non-orphan network clusters with 50TF-gene pairs, 8TF-TF pairs 6miRNA-TF pairs and 36 miRNA-gene pairs which later dissected into 16 subclusters. GO annotations revealed that a host of signals(hormone,growth factors-EGF /PDGF, thrombopoietin, oxidative stress,vitamin/nutrition) regulate MAPK signaling altering angiogenesis,JAK-STAT signaling,apoptosis, inflammatory and immune response and steroidogenesis in PCOS women.Thus, MAPK signaling is identified as the hub which is able to control the full breadth of this metabolic syndrome. Our data pave way to concentrate efforts on MAPK targeted therapeutic strategies in PCOS.
Authors - Divya Saro Varghese, Uma Chandran,Ambili Soumya,Sathy.M.Pillai,Krishnapillai Jayakrishnan,Prabhakara.P.Reddi,Pradeep.G.Kumar.
Loss of function of TAR DNA-binding protein (TDP-43)has been implicated in neurodegenerative disorders in bith humans and animal models.TDP-43 has also been shown to be cis-acting transcriptional repressor of the acrosome vesicle gene in mice.In the present study, we investigated the expression of the TDP-43 transcript(TARDBP) and protein in germ cells from 11 fertile and 98 subfertile men to verify its potential association with poor seminograms.The expression profile of TDP-43 was characterised in immature germ cells and spermatozoa from semen from fertile and subfertile men using reverse transcription-polymerase chain reaction, western blotting and immunoflurorescence.Although germ cells from subfertile men tested negative for TARDBP, the full-length message of the same was detected in fertile men.TDP-43 was detected in spermatazoa from fertile men using western blot analysis and immunoflurorescence.The expression of this protein was negligible in spermatozoa from men with primary spermatogenic dysfunction. We conclude that a deficiency in the TDP-43 expression is associated with defective spermatogenesis and male infertility. We propose that TDP-43 could be used as a marker of male factor infertility.
Authors - Indu S, Sreeja C. Sekhar,Sathy.M.Pillai , Malini Laloraya and Pradeep G. Kumar.
BACKGROUND: DYNLT1 is a member of a gene family identified within the t-complex of the mouse, which has been linked with male germ cell development and function in the mouse and the fly. Though defects in the expression of this gene are associated with male sterility in both these models, there has been no study examining its association with spermatogenic defects in human males. METHODS:In this study, we evaluated the expression of DYNLT1 in the germ cells of fertile human males and males suffering from spermatogenic defects. We screened fertile (n=15), asthenozoospermic (n=35), teratozoospermic (n=35) and oligozoospermic (n=28) males using PCR, real-time PCR and western blot analysis. RESULTS: We observed weak to negligible expression of DYNLT1 in patients from all the three infertility syndrome groups. Immunofluorescence analysis indicated the distribution of DYNLT1 over head, mid-piece and tail segments of spermatozoa. Spermatozoa from infertile males presented total absence of DYNLT1 in the tail region in situations where detectable levels of protein were present. However, majority of the patients showed negligible levels of localization of DYNLT1 on the spermatozoa. A bioinformatic analysis consolidated the known interactions of DYNLT1 in various systems. CONCLUSIONS: Defective expression of DYNLT1 was associated with male factor infertility syndromes in our study population. We have discussed the implications of these observations in the light of the known functions of DYNLT1, which included protein trafficking, membrane vesiculation, cell cycle regulation and stem cell differentiation.
Authors - Meera.B.Krishna, Annu Joseph, Belinda Dsilva, Sathy.M.Pillai, Malini Laloraya
Polycystic Ovarain Syndrome is the common endocrinopathy among reproductive aged women.Oxidative stress mediated endocrine dysfunction is a characteristic feature of PCOS, the mechanism of which is poorly understood.Our study reports that the level of NO and H2O2 in plasma of PCOS women are reduced in comparison with age-weight matched controls.We identified that the principal enzyme, endothelial nitric oxide synthase transcript was down regulated in PCOS on real time expression analysis thereby explaining the reduction in NO levels.eNOs activation would be further hindered due to low H2O2 levels despite high SOD2/SOD3 expression as a consequence of elevated catalase expression. Our results show that simultaneous decrease in argininosuccinate lyase(ASL) as well as L-Arginine transporter (SLC7A1) with elevated Arginase 1(ARG1)-the arginine degrading enzyme, is responsible for the extremely diminished supply pool of arginine observed in PCOS patients.Increased protein arginine methyltransferase 1 (PRMT1) and reduced Dimethylarginine dimethylaminohydralose 2 (DDAH2) explain Asymmetric dimethylarginine (ADMA) accumulation further impacting eNOS activity.Thus, our results cumulatively suggest a reduced NO due to low eNOS expression , its inhibition by dwindling supply of H2 O2 and high ADMA synthesis pathway compounded by reduced arginine bioavailability.
1 year fellowship Programme in Infertility / IVF Therapy