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Gestational-onset Hypothyroidism Affects Genes Controlling Epididymal Sperm Maturation in F1 Progeny Rats


Affiliations
1 Department of Medical Physiology, College of Medicine, Texas A & M Health Science Center, Bryan Campus, Texas – 77807, USA ., India
2 Department of ORAL Head and Neck Surgery, The University of Oklahoma Health Sciences Center, RP800, Research Parkway Suite 432, Oklahoma City – 73104, Oklahoma, USA ., India
3 Department of Endocrinology, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, India ., India
4 Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A and M Health Science Center, Reynolds Medical Building, College Station, Texas – 77843, USA ., India
5 One Bungtown Road, James Building, Cold Spring Harbor Laboratories, New York – 11724, USA ., India
     

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Purpose: Hypothyroidism is associated with infertility. We have reported that gestational-onset hypothyroidism impairs post-testicular sperm maturation in F1 progeny rats, whereas the underlying mechanism remains obscure. In this study, we tested the hypothesis “transient gestational-onset hypothyroidism affects post-testicular sperm maturation by inducing oxidative stress and modifying the expression of specific genes controlling epididymal function in F1 progeny rats”. Methods: Hypothyroidism was induced by providing 0.05% methimazole in drinking water to pregnant rats during specific periods of foetal differentiation of testis and epididymis. On the postnatal day 120, epididymes were dissected out and used for various analyses. Sperm parameters and activities of antioxidants and pro-oxidants were assayed using standard protocols. qRT-PCR and western blot were carried out to assess the expression of epididymal functional genes and their respective proteins. Results: Gestational-onset hypothyroidism produced decrease of sperm motility and membrane integrity, and increase of abnormal sperm morphologies. While the concentration of reduced glutathione and specific activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase decreased, levels of pro-oxidants hydrogen peroxide and lipid peroxidation increased. Expression levels of androgen and thyroid hormone receptors α/β, aquaporin 9, and glutathione peroxidise 5 decreased, whereas estrogen receptors α/β increased in rats with gestational-onset hypothyroidism. Conclusion: Our results support our hypothesis and we conclude that gestationalonset hypothyroidism impairs post-testicular sperm maturation due to oxidative stress and modified expression of nuclear hormone receptors and aquaporin 9 in the epididymis of F1 progeny.

Keywords

Androgen Receptor, Antioxidants, Aquaporin 9, Estrogen Receptors, Thyroid Hormone Receptor
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  • Gestational-onset Hypothyroidism Affects Genes Controlling Epididymal Sperm Maturation in F1 Progeny Rats

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Authors

Navaneethabalakrishnan Shobana
Department of Medical Physiology, College of Medicine, Texas A & M Health Science Center, Bryan Campus, Texas – 77807, USA ., India
Sadhasivam Balaji
Department of ORAL Head and Neck Surgery, The University of Oklahoma Health Sciences Center, RP800, Research Parkway Suite 432, Oklahoma City – 73104, Oklahoma, USA ., India
Navaneethabalakrishnan Shobana
Department of Endocrinology, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, India ., India
Navaneethabalakrishnan Shobana
Department of Medical Physiology, College of Medicine, Texas A & M Health Science Center, Bryan Campus, Texas – 77807, USA ., India
Ajit Kumar Navin
Department of Endocrinology, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, India ., India
Ajit Kumar Navin
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A and M Health Science Center, Reynolds Medical Building, College Station, Texas – 77843, USA ., India
Jaganathan Anbalagan
Department of Endocrinology, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, India ., India
Jaganathan Anbalagan
One Bungtown Road, James Building, Cold Spring Harbor Laboratories, New York – 11724, USA ., India
Bhaskaran Ravi Sankar
Department of Endocrinology, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, India ., India
Ramachandran Ilangovan
Department of Endocrinology, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, India ., India
Mariajoseph Michael Aruldhas
Department of Endocrinology, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600113, India ., India

Abstract


Purpose: Hypothyroidism is associated with infertility. We have reported that gestational-onset hypothyroidism impairs post-testicular sperm maturation in F1 progeny rats, whereas the underlying mechanism remains obscure. In this study, we tested the hypothesis “transient gestational-onset hypothyroidism affects post-testicular sperm maturation by inducing oxidative stress and modifying the expression of specific genes controlling epididymal function in F1 progeny rats”. Methods: Hypothyroidism was induced by providing 0.05% methimazole in drinking water to pregnant rats during specific periods of foetal differentiation of testis and epididymis. On the postnatal day 120, epididymes were dissected out and used for various analyses. Sperm parameters and activities of antioxidants and pro-oxidants were assayed using standard protocols. qRT-PCR and western blot were carried out to assess the expression of epididymal functional genes and their respective proteins. Results: Gestational-onset hypothyroidism produced decrease of sperm motility and membrane integrity, and increase of abnormal sperm morphologies. While the concentration of reduced glutathione and specific activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase decreased, levels of pro-oxidants hydrogen peroxide and lipid peroxidation increased. Expression levels of androgen and thyroid hormone receptors α/β, aquaporin 9, and glutathione peroxidise 5 decreased, whereas estrogen receptors α/β increased in rats with gestational-onset hypothyroidism. Conclusion: Our results support our hypothesis and we conclude that gestationalonset hypothyroidism impairs post-testicular sperm maturation due to oxidative stress and modified expression of nuclear hormone receptors and aquaporin 9 in the epididymis of F1 progeny.

Keywords


Androgen Receptor, Antioxidants, Aquaporin 9, Estrogen Receptors, Thyroid Hormone Receptor

References