Manjit K Sharma alias Gill alias Gill-Sharma
I have 3 papers published under my maiden name: M Gill. These are my PhD thesis papers. I did my PhD from Neurochemistry Dept, C.N.R.S, Strasbourg, France affiliated to Louis Pasteur University. Thereafter I returned to India and joined CSIR, as Pool officer and worked in Institute for Research in Reproduction. I joined the same institute as Assistant Research officer after one year. It comes under Indian Council of Medical Research, New Delhi. The institute has now been upgraded to a national institution and renamed as NATIONAL INSTITUTE FOR RESEARCH IN REPRODUCTIVE HEALTH, based in Mumbai, India. I have now retired as Head of NEUROENDOCRINOLOGY Dept which I joined in 1980 as Assistant Research officer. My papers are published under different names depending upon my marital status: M Gill/M.K Sharma/ Manjit Gill-Sharma.
Supervisors: Prof Paul MANDEL (PhD advisor); Dr G Mack and Dr E Kempf (co-advisors); Dr K.N Sarin (MSC advisor) and Dr H.S.Juneja (postdoc supervisor)
Phone: 09819307305
Address: A-602/WINCHESTER apts, 2nd Cross Lane,
Lokhandwala Complex, Andheri (W), Mumbai 400053, India
Supervisors: Prof Paul MANDEL (PhD advisor); Dr G Mack and Dr E Kempf (co-advisors); Dr K.N Sarin (MSC advisor) and Dr H.S.Juneja (postdoc supervisor)
Phone: 09819307305
Address: A-602/WINCHESTER apts, 2nd Cross Lane,
Lokhandwala Complex, Andheri (W), Mumbai 400053, India
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Papers by Manjit K Sharma alias Gill alias Gill-Sharma
levels of luteinizing hormone (LH) and testosterone (T) with
no effect on follicle-stimulating hormone (FSH) and prolactin (PRL). It reduces the male rat’s ability to inseminate the female (potency), as well as its siring ability (fecundity). The objective of the present study was to test whether androgen supplementation could reverse all or some of the observed effects of TAM. To obviate the effects of estrogen, the study was designed to evaluate the beneficial or deleterious effect of 5-dihydrotestosterone (DHT), a 5-reduced, nonaromatizable metabolite of T, on the reproductive functions of TAM-treated adult male rats. Adult male rats received either saline
or TAM (0.2 or 0.4 mg per day PO) for 90 days. A group of TAM treated rats was implanted with 6 mg DHT from day 50 to day 90 A third group of untreated animals was implanted with 0-, 1-, 3-, or 6-mg DHT implants for 90 days. Mating studies were done to assess the fecundity, potency, and fertility index at the end of the treatment. Weights of testes, pituitary, and accessory sex organs were recorded, and circulating levels of LH, FSH, PRL, T, and 17--estradiol were estimated. DHT did not affect the fecundity or fertility index. TAM reduced fecundity, potency, and the fertility index. DHT implants improved the fertilizing ability of the TAM-treated male rat. This study discusses and reviews the role of T and 17--estradiol in sperm-fertilizing potential in light of these observations.
or more reproductive hormones viz. LH, FSH, testosterone and reduced their
siring ability. The reduction in epididymal sperm counts was not considerable after treatment with these drugs, but conventional methods of assessment of spermatozoa quality viz. sperm chromatin structure assay (SCSA), nuclear
chromatin decondensation (NCD) assay, monobromobimane (mBBr) uptake, had shown quantifiable changes in caput sperm chromatin compaction and reduced the testicular levels of protamine 1. The present follow-up study attempts to quantify changes in caudal sperm chromatin which has undergone
compaction in the epididymis, in the altered hormonal microenvironment of rats treated with cyproterone acetate, tamoxifen citrate, fluphenazine decanoate, oestradiol valerate, at doses of 50, 5.77, 0.71, 0.28 lmol kg)1 body weight respectively given for periods of 15, 60, 60, 10 days, with a view to correlating these changes to reduction in their fertilising potential. During the androgen dependent transit of spermatozoa from caput to cauda epididymis, thiol group
oxidation and tyrosine phosphorylation of protamine occurs in maturing sperms concomitant with development of fertilising ability. The results indicate that conventional methods viz. SCSA, NCD, mBBr uptake fail to detect changes induced by hormone deficits in sperm chromatin condensation, as a result of maturation during transit from caput to cauda epididymis. Absence of protamine1 in epididymal sperm was observed in either testosterone or FSH deficient rats that correlated with reduced fertilising potential. The study suggests that changes in LH/T or FSH affect a hitherto unknown common molecular
mechanism in the testis, underlying the protamination of rat spermatozoa. In conclusion, loss of P1 occurs in adult male rats deprived of T or FSH and is a reliable detectable change in epididymal sperm indicative of chromatin condensation
defects associated with endocrine imbalance and poor fertility status.
underlying chromatin condensation remains poorly understood. In the past decade, we developed two adult male
rat models wherein functional deficits of testosterone or FSH, produced after treatments with 20 mg/Kg/d of cyproterone acetate (CPA) per os, for a period of 15 days or 3 mg/Kg/d of fluphenazine decanoate (FD) subcutaneously, for a period of 60 days, respectively, affected the rate of sperm chromatin decondensation in vitro.
These rat models have been used in the current study in order to delineate the putative roles of testosterone and
FSH in the molecular mechanism underlying remodelling of sperm chromatin.
Results: We report that deficits of both testosterone and FSH affected the turnover of polyubiquitylated histones and led to their accumulation in the testis. Functional deficits of testosterone reduced expression of MIWI, the 5-methyl cap binding RNA-binding protein (PIWIlike murine homologue of the Drosophila protein PIWI/P-element induced wimpy testis) containing a PAZ/Piwi-Argonaut-Zwille domain and levels of histone deacetylase1 (HDAC1), ubiquitin ligating enzyme (URE-B1/E3), 20S proteasome α1 concomitant with reduced expression of ubiquitin activating enzyme (ube1), conjugating enzyme (ube2d2), chromodomain Y like protein (cdyl), bromodomain testis specific protein (brdt), hdac6 (histone deacetylase6), androgen-dependent homeobox placentae embryonic protein (pem/RhoX5), histones h2b and th3 (testis-specific h3). Functional deficits of FSH reduced the expression of cdyl and brdt genes in the testis, affected turnover of ubiquitylated histones, stalled the physiological DNA repair
mechanism and culminated in spermiation of DNA damaged sperm.
Conclusions: We aver that deficits of both testosterone and FSH differentially affected the process of sperm chromatin remodelling through subtle changes in the ‘chromatin condensation transcriptome and proteome’, thereby stalling the replacement of ‘dynamic’ histones with ‘inert’ protamines, and altering the epigenetic state of condensed sperm chromatin. The inappropriately condensed chromatin affected the sperm chromatin cytoarchitecture, evident from subtle ultrastructural changes in the nuclei of immature caput epididymal sperm of
CPA- or FD-treated rats, incubated in vitro with dithiothreitol.
laboratory have shown that administration of 17-beta estradiol at a dose of 100g/kg body weight for 10 d resulted in failure of spermiation. This was accompanied by a suppression of FSH and intratesticular
testosterone with a concomitant rise in intratesticular 17- beta estradiol. The present study was undertaken to determine the cause of failure and subsequently the molecular events in spermiation. Electron microscopic and confocal studies revealed an absence of tubulobulbar complex in step 19 spermatids after estradiol treatment, highlighting the significance of these structures in spermiation. It was further observed that treatment affected the Sertoli cell cytoskeleton and Arp2/3 complex that is critical for de novo polymerization of actin during tubulobulbar complex formation. In conclusion, the present study reports the role of 17-beta estradiol in inhibiting the formation of tubulobulbar complex, which could be one of the mechanism by which environmental estrogens influence male fertility.
intratesticular estradiol. The study was based on the fact that administration of exogenous estradiol suppresses the hypothalamus pituitary gonadal axis (HPG) with a dose-dependant concomitant increase in intratesticular estrogen levels. Three doses of 17- beta estradiol, namely 20, 100 and 200 g/kg/day were administered subcutaneously to different batches of adult male rats for 10 days. The effect of the three
doses on serum hormonal profile, intratesticular testosterone (T) and estradiol (E) levels were studied. Twenty micrograms per kilograms per day of 17-beta estradiol affected the hypothalamus–pituitary axis, reducing serum gonadotropins and intratesticular testosterone; however, 100g/kg/day of 17- estradiol decreased serum FSH and intratesticular testosterone, increased intratesticular estradiol, but had no effect on serum LH. Interestingly, 200 g/kg/day of 17- beta estradiol decreased serum and intratesticular T without any effect on serum gonadotropins. This could be attributed to the positive feedback effect of estrogens on gonadotropins. In the testis, morphologically two visible effects were seen, namely ‘spermiation failure’ in all three doses attributed to the suppression of T and FSH and a ‘maintenance effect’ in the 100 g/kg/day attributed to E and/or 10% of available intratesticular T. The direct effect of an increase in intratesticular estradiol levels was observed in terms of a decrease in apoptosis in germ cell. The study, therefore, suggests that 100 g/kg/day of 17- beta estradiol could be used to study the effects of high intratesticular estradiol with a concomitant decrease in intratesticular T and serum FSH levels on spermatogenesis.
change in membrane integrity, lipid peroxidation, ATP levels and activities of glycolytic enzymes, creatine kinase and PKC.