The Department of Gamete Immunobiology is committed towards research on the male gamete (sperm) in particular with a view to understand the functional intricacies involved in imparting sperm its ability to move/swim towards and fertilize the oocyte. Asthenozoospermia accounts for almost 50% of the cases of male infertility. Our study investigating phosphoproteins differentially expressed in asthenozoosperm has identified the phosphoproteins relevant to sperm motility and the signature molecules likely to be altered in asthenozoospermia. Indepth studies are being conducted to delineate the role of a few of these candidate proteins. GRP78 is one such candidate protein that is being investigated for its role in sperm motility. Our studies investigating the role of reversible acetylation of alpha tubulin in sperm function have demonstrated the differential expression of acetylable alpha tubulin isoforms in the normal- and asthenozoosperm at protein and transcript level. We have shown the presence of transcript and protein of alpha tubulin specific deacetylase HDAC6 in rat sperm. This has not been reported earlier and further showed that it is catalytically active and inhibitors of HDAC6 increase acetylation and restrict sperm motility. On the basis of our observations with the human and rat sperm and the available literature we believe that HDAC6 may be required to maintain dynamic instability in sperm flagella, and that dynamic instability may be a pre-requisite for normal sperm motility and this aspect is presently being investigated. We are also working towards developing a HDAC6 overexpressing rat model with a view to understanding the role of HDAC6 in spermatogenesis. In collaboration with IIT, Mumbai we are working towards development of a microfluidic device for good quality sperm selection for Assisted Reproductive Technologies.
Another aspect of sperm motility under investigation is the precise role of outer dense fibres (ODFs) in the coordinated action of both the microtubule sliding and the elastic recoil provided by ODFs to navigate the varying viscosity and pH of the reproductive tract fluids. ODFs are disulphide containing proteins which are stabilized by cross-linking during epididymal maturation. One such protein, macrophage migratory factor (MIF) a moonlighting oxidoreductase is internalized by sperm from the epididymal fluid. Current research involves identification and characterization of such ODF binding partners from both male and female reproductive tract fluids as well as their mechanism of internalization.
The lab is also involved in elucidating the aetiology of autoimmune premature insufficiency (aPOI) which often is detected late in most women undergoing IVF. It is almost always seen in conjunction with an autoimmune disease, especially thyroid or adrenal. Being a multifactorial disorder, designing a better biomarker for early diagnosis has been difficult despite several efforts over a period of time worldwide. This entails better symptomatic relief as only recourse. Osteoporosis due to low estrogen levels and vitamin D deficiency is common in these women. Since vitamin D deficiency has been implicated in almost all autoimmune diseases, efforts are on to investigate role of vitamin D deficiency in aPOI.