Submited on: 06 May 2013 05:52:25 PM GMT
Published on: 07 May 2013 08:38:04 AM GMT
 
Review
Posted by Prof. Kulvinder K Kaur on 13 May 2013 08:35:41 AM GMT

  • What are the main claims of the paper and how important are they?

    This is an extension of the work of the authors in experimentally induced hypothyroidism using PTU which they have been working on and proved oxidative stress leading to germ cell depletion by both transient and persistent hypothyroidism-here they have used TUNEL method to demonstrate increased germ cell apoptosis in both transient and persistent hypothyroidism as compared to their controversial increased germ cells in transient hypothyroidism cases in earlier studies and shoewed here in both cases thjere was increased germ cell apoptosis whiich ultimately leads to impaired fertility in adulthood and the mechanism of apoptosis is by anoikis a novel mechanism proposed by Frisch et al where apoptosis is triggered by the loss of appropriate integrin mediated cell-matrix contact causing cell survival to be anchorage dependent.Although the work has importance in treatment of human infertility treatment with thyroid disorders the authors need to correct the syntax with relation to line 13 where they have mentioned thyroid hormone is associated with abnormal sexual function and fertility-rather than either hyper or hypo or abnormal thyroid function and need to correct line we also  marked changes in germ cell numbers in line 33 of 2nd paragraph of introduction.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    Basically author himself published in 2012 on this subject 1)Sahoo DK,Anita R Compromised rat testicular antioxidant defence system by hypothyroidism before puberty.I J of Endocrinology 2012;Aer ID-637825,11 Pages2)Gilleron J,Nebout M,Scarabeelli L,Senegas-Balas F,Palmero S,Segretain D,Pointis G.A potential novel mechanism involving connexin 43 gap junction for control of sertoli cell proliferation by thyroid hormones.J Cell Physiol 2006;209(1):153-161.3)Anbalagan J,Sashi MA,Venkatesh G,Stanlety JA,Neelamohan R,Aruldhas MM.Mechanism underlying transient gestation -onset hypothyroidism-induced impairment of posttesticular sperm maturation in rat.Fert Steril 2010;93(8):2491-2497.4) 4) Maran RR,Aeuldhas MM-Adverse effects of neonatal hypothyroidism on wistar spermatogenesis-Endocr Res 2002;28(3):141-154.5)Aruldhas MM,Ramalingam N,Jaganathan A,John Sashi AM,Stanley JANagappan ASVasavan J,Kannan A,Seshadri VN Gestational and neonatal -onset hypothyroidism alters androgen receptor in rat prostate gland s at adsulthood.Perostate 2010;70(7):689-700.while this group of Aruldhas MM has been working using methimazole the author has been working using PTU like JanniniEA et al6)Ulisse S,Rucci N,Piersanti D,Carosa E,Graziano FM,Pavan A,Ceddia P,Arizzi M,Muzi P,Cironi L,Gnessi L,D;Armiento M,Jannini EA.Regulation by thyroid hormone of the expression of basement membrane components in rat prepubertal sertoli cells.Endocrinology 1998;139(2):741-747.


  • Are the claims properly placed in the context of the previous literature?

    Yes


  • Do the results support the claims? If not, what other evidence is required?

    Yes


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    The author has not provided data regarding oxidative changes -only tried to do hormonal studies and apoptosis by staining and the TUNEL studies hence should not use abbreviations for enzymes like SOD,CAT ,GR and provide details of abbreviations for all antioxidative enzymes or for lipid peroxidation than usung same as for his previous paper.


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    Firstly the author shoyld improve the introduction lines which gets misinterpreted in line 11 &2nd paragraph add    we also observed marked changes in germ cell numbers before marked and correct thyroid hormone is associated with abnormal sexual function and infertility and add the details of all enzymes mentioned like glutathione reductase,catalase,superoxide dysmutase,reduced gltathione etc rather than just mentioning the abbreviations and details of whether these enzymes were tested during TUNEL testing also.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    No-it is just an extension of work and similar work and lot of reviews available on role of thyroid in testicular function


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    Besides the effect of thyroid hormones on antioxidant in testis and causing oxidative stress in various organs like brain ,heartmmuscle,liver other important roles of thyroid maybe in affecting AMH, AR, connexin 43 levels which mayhave important effect oin sertoli cell proliferation and maturation  and regulate sertoli cell development by regulating thyroid hormone receptor alpha 1 and also importantly Janninis geoup showed that thyroid hormone mainly T3 treatment increased staining of laminin and entactin while reduced grade IV collagen in sertoli cells and showing the anoikis mechanism is by this mechnism by abffecting extracellular matrix and also it regulates glut 1&8 receptors for regulating ,metabolism as shown by Jannini et al.


  • Other Comments:

    None

  • Competing interests:
    None
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:

    None

  • Experience and credentials in the specific area of science:

    Yes I have been practicing reproductive endocrinology and infertility for over 25 years

  • How to cite:  Kaur K K.Review[Review of the article 'Increased germ cell apoptosis during testicular development and maturation by experimentally induced transient and persistent hypothyroidism ' by Sahoo D].WebmedCentral 2013;4(5):WMCRW002726
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I am very much thankful to Prof. Kaur for critically evaluating the paper “Sahoo DK. Increased germ cell apoptosis during testicular development and maturation by experimentally induced transient and persistent hypothyroidism. WebmedCentral ENDOCRINOLOGY 2013;4(5):WMC004235”. I really appreciate you for your helpful suggestions and I am including these in the paper In Introduction section “Hypo- and hyperthyroid states are associated with abnormal sexual function and infertility (Maqsood 1950; Chowdhury et al. 1984; Gerhard et al. 1991; Cooke and Meisami 1991; Palmero et al. 1994; Jannini et al. 1995; Sahoo et al. 2005; 2007; 2008a; 2008b; Sahoo, 2011; Sahoo and Roy 2012).” “Marked changes in germ cell population, Sertoli cell counts and seminiferous tubule diameter were noticed in persistent and transient hypothyroid rat testis (Sahoo et al. 2008b).” Abbreviations LPx: Lipid Peroxidation SOD: Superoxide dismutase CAT: Catalase GPx: Glutathione peroxidase GR: Glutathione reductase GSH: Reduced glutathione I would like to state that all the antioxidant parameters and oxidative stress parameters were evaluated and the data are similar to the data already published in the following paper (sahoo et al., 2008) and hence are not included in this paper. Reference Sahoo DK, Roy A, Bhanja S, Chainy GBN, 2008: Hypothyroidism impairs antioxidant defence system and testicular physiology during development and maturation. Gen Comp Endocrinol 156, 63-70. I agree with Prof. Kaur that this work is an extension of our previous studies (Sahoo and Roy, 2012 and Sahoo et al., 2008; Sahoo et al., 2006). I understand that there are number of papers available related to oxidative stress in different tissues and in various condition, however, this research paper is focused only on testicular germ cell apoptosis related to hypothyroid induced oxidative stress.
Responded by Dr. Dipak K Sahoo on 19 May 2013 01:44:05 AM

  • What are the main claims of the paper and how important are they?

    The investigator has developed an experimental animal model by administering  6-n-propyl-2-thiouracil (PTU) to induce transient and persistent hypothyroidism. The paper is supported by experimental evidence showing apoptosis by employing tunnel assay. This is important field of reserach and a great challenge to findout the effect of changes in thyroid hormone and mechanism of its effect.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    Yes the claims are novel and supported by experimetal results. 


  • Are the claims properly placed in the context of the previous literature?

    Yes.


  • Do the results support the claims? If not, what other evidence is required?

    Yes the experimental result support the claim that administration of PTU  induce apoptosis in germ cells. It would have been more convincing and stronger if he can add changes in gene and protein expression datas related to apoptosis.


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    NA


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    Yes the methodology section is well written.


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    The paper is great. Here are few suggestions to improve the paper.

     

    1. Examination of changes in genes and protein level related to apoptosis, cell death and oxidative stress pathways with the administration of PTU at different time points.

    2. staining with key apoptotic markers like caspase-3, poly(ADP-ribose) polymerase (PARP) .

    3. USe of Ko mice, specific inhibitors to block specific  pathways  can further dissect the mechanism of germ cell apoptosis with chnages in thyroid hormone.


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    This paper is outstanding for following reaosn

     

    a. very well written with proper citation of previous literature

    b. The methodology and figure legends are written well .

     

     


  • Other Comments:

    Overall this is a good paper.

  • Competing interests:
    None
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    Yes
  • References:

    Molecular characterization of a Brugia malayi transglutaminase E Devarajan, PK Mishra, S Thirugnanam, K Mehta, R Chandrashekar, K Perumal Parasitology research 93 (2), 145-150

  • Experience and credentials in the specific area of science:

    Molecular characterization of a Brugia malayi transglutaminase E Devarajan, PK Mishra, S Thirugnanam, K Mehta, R Chandrashekar, K Perumal Parasitology research 93 (2), 145-150

  • How to cite:  Mishra P K.Increased Germ Cell Apoptosis During Testicular Development and Maturation by Experimentally Induced Transient and Persistent Hypothyroidism[Review of the article 'Increased germ cell apoptosis during testicular development and maturation by experimentally induced transient and persistent hypothyroidism ' by Sahoo D].WebmedCentral 2013;4(5):WMCRW002719
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I really appreciate Dr. Mishra for critically evaluating the paper “Increased Germ Cell Apoptosis During Testicular Development and Maturation by Experimentally Induced Transient and Persistent Hypothyroidism” and providing thoughtful feedbacks and suggestions. I agree with Dr. Mishra that changes in gene and protein expression data related to apoptosis would be more convincing our present findings. In the future study, we will focus on different key apoptotic markers like caspase-3, poly (ADP-ribose) polymerase (PARP) at different time points of experimentally induced hypothyroidism. We will also look onto the changes in genes and protein level related to apoptosis, cell death and oxidative stress pathways with the administration of PTU at different time points and we will study the mechanism of germ cell apoptosis with changes in thyroid hormone by using Ko mice. Thank you very much Dr. Mishra.
Responded by Dr. Dipak K Sahoo on 19 May 2013 01:47:22 AM