Ameliorative effect of combined low dose of Pioglitazone and omega‐3 on spermatogenesis and steroidogenesis in diabetic rats

Background Chronic hyperglycemia is linked to either subfertility or infertility among diabetic males. Pioglitazone is one of the thiazolidinediones (TZDs) drugs that are selective peroxisome proliferator‐activated receptor (PPAR‐γ agonists used for treating type 2 diabetes mellitus (T2DM). Aim This...

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Veröffentlicht in:Journal of cellular biochemistry 2020-02, Vol.121 (2), p.1524-1540
Hauptverfasser: Hasan, Mai M., El‐Shal, Amal S., Mackawy, Amal M. H., Ibrahim, Ebtesam M., Abdelghany, Eman M. M. A., Saeed, Abeer A., El‐Gendy, Jehan
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container_end_page 1540
container_issue 2
container_start_page 1524
container_title Journal of cellular biochemistry
container_volume 121
creator Hasan, Mai M.
El‐Shal, Amal S.
Mackawy, Amal M. H.
Ibrahim, Ebtesam M.
Abdelghany, Eman M. M. A.
Saeed, Abeer A.
El‐Gendy, Jehan
description Background Chronic hyperglycemia is linked to either subfertility or infertility among diabetic males. Pioglitazone is one of the thiazolidinediones (TZDs) drugs that are selective peroxisome proliferator‐activated receptor (PPAR‐γ agonists used for treating type 2 diabetes mellitus (T2DM). Aim This study aims to explore the possible effect of low Pioglitazone dose and omega (ω‐3) on rat male reproductive function. Furthermore, we evaluated the add‐on effect of combined use of low Pioglitazone dose of and ω‐3 on reproductive functions in adult male T2DM rats. Methods Fifty adult male rats were included and subdivided into control and four test subgroups. T2DM was induced in test groups and subdivided into non‐treated T2DM, ω‐3 treated, 0.6 mg/kg Pioglitazone treated, and combined treated group (orally by gavage). Following 16 weeks, final body weight, testicular weight, fasting plasma glucose, and serum testosterone levels were measured. Semen analysis, testicular testosterone, malondialdehyde (MDA) concentrations, superoxide dismutase (SOD) activity, immunohistochemistry staining for apoptosis marker B‐cell lymphoma protein 2 (Bcl‐2), proliferation marker as proliferating cell nuclear antigen (PCNA), estrogen receptor α (ERα), androgen receptor (AR) were determined. Caspase‐3, nuclear factor‐kappa B (NF‐kB), glucose transporter 3 (GLUT3), 17β‐hydroxysteroid dehydrogenases (17β‐HSD) PPARγ, and PPARα genes expression were analyzed by real‐time polymerase chain reaction (RT‐PCR). Results Our findings revealed that treatment with low dose of Pioglitazone or ω‐3 significantly lowered fasting plasma glucose and MDA levels, ameliorated diabetes effects on histological damage, improved antioxidant activity (SOD), significantly improved anti‐apoptosis BCL‐2 and proliferation (PCNA), remarkably elevated ERα, AR, 17β‐HSD PPARγ, and PPARα expression with significant reduction in caspase‐3, NF‐kB genes expression and improved semen quality as well. Combined use of low dose of and ω‐3 has better effects on all measured parameters. Conclusion Small Pioglitazone dose and ω‐3 possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; while combined use of both has an add‐on effect. Combined use of low dose of and omega‐3 has better effects on all measured parameters. Thus, small dose of and omega‐3 fatty acids possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; notably use of both has an add‐on
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H. ; Ibrahim, Ebtesam M. ; Abdelghany, Eman M. M. A. ; Saeed, Abeer A. ; El‐Gendy, Jehan</creator><creatorcontrib>Hasan, Mai M. ; El‐Shal, Amal S. ; Mackawy, Amal M. H. ; Ibrahim, Ebtesam M. ; Abdelghany, Eman M. M. A. ; Saeed, Abeer A. ; El‐Gendy, Jehan</creatorcontrib><description>Background Chronic hyperglycemia is linked to either subfertility or infertility among diabetic males. Pioglitazone is one of the thiazolidinediones (TZDs) drugs that are selective peroxisome proliferator‐activated receptor (PPAR‐γ agonists used for treating type 2 diabetes mellitus (T2DM). Aim This study aims to explore the possible effect of low Pioglitazone dose and omega (ω‐3) on rat male reproductive function. Furthermore, we evaluated the add‐on effect of combined use of low Pioglitazone dose of and ω‐3 on reproductive functions in adult male T2DM rats. Methods Fifty adult male rats were included and subdivided into control and four test subgroups. T2DM was induced in test groups and subdivided into non‐treated T2DM, ω‐3 treated, 0.6 mg/kg Pioglitazone treated, and combined treated group (orally by gavage). Following 16 weeks, final body weight, testicular weight, fasting plasma glucose, and serum testosterone levels were measured. Semen analysis, testicular testosterone, malondialdehyde (MDA) concentrations, superoxide dismutase (SOD) activity, immunohistochemistry staining for apoptosis marker B‐cell lymphoma protein 2 (Bcl‐2), proliferation marker as proliferating cell nuclear antigen (PCNA), estrogen receptor α (ERα), androgen receptor (AR) were determined. Caspase‐3, nuclear factor‐kappa B (NF‐kB), glucose transporter 3 (GLUT3), 17β‐hydroxysteroid dehydrogenases (17β‐HSD) PPARγ, and PPARα genes expression were analyzed by real‐time polymerase chain reaction (RT‐PCR). Results Our findings revealed that treatment with low dose of Pioglitazone or ω‐3 significantly lowered fasting plasma glucose and MDA levels, ameliorated diabetes effects on histological damage, improved antioxidant activity (SOD), significantly improved anti‐apoptosis BCL‐2 and proliferation (PCNA), remarkably elevated ERα, AR, 17β‐HSD PPARγ, and PPARα expression with significant reduction in caspase‐3, NF‐kB genes expression and improved semen quality as well. Combined use of low dose of and ω‐3 has better effects on all measured parameters. Conclusion Small Pioglitazone dose and ω‐3 possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; while combined use of both has an add‐on effect. Combined use of low dose of and omega‐3 has better effects on all measured parameters. Thus, small dose of and omega‐3 fatty acids possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; notably use of both has an add‐on effect.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.29388</identifier><identifier>PMID: 31709631</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Androgen receptors ; Animals ; Antigens ; Antioxidants ; Apoptosis ; Beta cells ; Body weight ; Caspase ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Experimental - complications ; Diabetes Mellitus, Experimental - pathology ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - pathology ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Estrogens ; Fasting ; Fatty Acids, Omega-3 - administration &amp; dosage ; Fatty Acids, Omega-3 - pharmacology ; Fertility ; Gene expression ; Genes ; Glucose ; Glucose transporter ; Hyperglycemia ; Hypoglycemic Agents - pharmacology ; Immunohistochemistry ; Infertility ; Infertility, Male - drug therapy ; Infertility, Male - etiology ; Infertility, Male - metabolism ; Infertility, Male - pathology ; Lymphoma ; Male ; Males ; Malondialdehyde ; Markers ; omega‐3 ; Peroxisome proliferator-activated receptors ; Pioglitazone ; Pioglitazone - administration &amp; dosage ; Pioglitazone - pharmacology ; Polymerase chain reaction ; PPAR ; PPAR alpha ; Proliferating cell nuclear antigen ; rat male fertility ; Rats ; real‐time polymerase chain reaction ; Semen ; Semen Analysis ; Spermatogenesis ; Steroidogenesis ; Subgroups ; Superoxide dismutase ; Testes ; Testis - drug effects ; Testis - metabolism ; Testis - pathology ; Testosterone ; Testosterone - metabolism ; Thiazolidinediones</subject><ispartof>Journal of cellular biochemistry, 2020-02, Vol.121 (2), p.1524-1540</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3538-a6f1c918e48f2535cb1972cc840e8ae55ec2d9da28cae5d884bd6676681ead643</citedby><cites>FETCH-LOGICAL-c3538-a6f1c918e48f2535cb1972cc840e8ae55ec2d9da28cae5d884bd6676681ead643</cites><orcidid>0000-0003-2167-8841</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.29388$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.29388$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31709631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hasan, Mai M.</creatorcontrib><creatorcontrib>El‐Shal, Amal S.</creatorcontrib><creatorcontrib>Mackawy, Amal M. H.</creatorcontrib><creatorcontrib>Ibrahim, Ebtesam M.</creatorcontrib><creatorcontrib>Abdelghany, Eman M. M. A.</creatorcontrib><creatorcontrib>Saeed, Abeer A.</creatorcontrib><creatorcontrib>El‐Gendy, Jehan</creatorcontrib><title>Ameliorative effect of combined low dose of Pioglitazone and omega‐3 on spermatogenesis and steroidogenesis in diabetic rats</title><title>Journal of cellular biochemistry</title><addtitle>J Cell Biochem</addtitle><description>Background Chronic hyperglycemia is linked to either subfertility or infertility among diabetic males. Pioglitazone is one of the thiazolidinediones (TZDs) drugs that are selective peroxisome proliferator‐activated receptor (PPAR‐γ agonists used for treating type 2 diabetes mellitus (T2DM). Aim This study aims to explore the possible effect of low Pioglitazone dose and omega (ω‐3) on rat male reproductive function. Furthermore, we evaluated the add‐on effect of combined use of low Pioglitazone dose of and ω‐3 on reproductive functions in adult male T2DM rats. Methods Fifty adult male rats were included and subdivided into control and four test subgroups. T2DM was induced in test groups and subdivided into non‐treated T2DM, ω‐3 treated, 0.6 mg/kg Pioglitazone treated, and combined treated group (orally by gavage). Following 16 weeks, final body weight, testicular weight, fasting plasma glucose, and serum testosterone levels were measured. Semen analysis, testicular testosterone, malondialdehyde (MDA) concentrations, superoxide dismutase (SOD) activity, immunohistochemistry staining for apoptosis marker B‐cell lymphoma protein 2 (Bcl‐2), proliferation marker as proliferating cell nuclear antigen (PCNA), estrogen receptor α (ERα), androgen receptor (AR) were determined. Caspase‐3, nuclear factor‐kappa B (NF‐kB), glucose transporter 3 (GLUT3), 17β‐hydroxysteroid dehydrogenases (17β‐HSD) PPARγ, and PPARα genes expression were analyzed by real‐time polymerase chain reaction (RT‐PCR). Results Our findings revealed that treatment with low dose of Pioglitazone or ω‐3 significantly lowered fasting plasma glucose and MDA levels, ameliorated diabetes effects on histological damage, improved antioxidant activity (SOD), significantly improved anti‐apoptosis BCL‐2 and proliferation (PCNA), remarkably elevated ERα, AR, 17β‐HSD PPARγ, and PPARα expression with significant reduction in caspase‐3, NF‐kB genes expression and improved semen quality as well. Combined use of low dose of and ω‐3 has better effects on all measured parameters. Conclusion Small Pioglitazone dose and ω‐3 possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; while combined use of both has an add‐on effect. Combined use of low dose of and omega‐3 has better effects on all measured parameters. Thus, small dose of and omega‐3 fatty acids possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; notably use of both has an add‐on effect.</description><subject>Androgen receptors</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Beta cells</subject><subject>Body weight</subject><subject>Caspase</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Therapy, Combination</subject><subject>Estrogens</subject><subject>Fasting</subject><subject>Fatty Acids, Omega-3 - administration &amp; dosage</subject><subject>Fatty Acids, Omega-3 - pharmacology</subject><subject>Fertility</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Glucose</subject><subject>Glucose transporter</subject><subject>Hyperglycemia</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Immunohistochemistry</subject><subject>Infertility</subject><subject>Infertility, Male - drug therapy</subject><subject>Infertility, Male - etiology</subject><subject>Infertility, Male - metabolism</subject><subject>Infertility, Male - pathology</subject><subject>Lymphoma</subject><subject>Male</subject><subject>Males</subject><subject>Malondialdehyde</subject><subject>Markers</subject><subject>omega‐3</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Pioglitazone</subject><subject>Pioglitazone - administration &amp; dosage</subject><subject>Pioglitazone - pharmacology</subject><subject>Polymerase chain reaction</subject><subject>PPAR</subject><subject>PPAR alpha</subject><subject>Proliferating cell nuclear antigen</subject><subject>rat male fertility</subject><subject>Rats</subject><subject>real‐time polymerase chain reaction</subject><subject>Semen</subject><subject>Semen Analysis</subject><subject>Spermatogenesis</subject><subject>Steroidogenesis</subject><subject>Subgroups</subject><subject>Superoxide dismutase</subject><subject>Testes</subject><subject>Testis - drug effects</subject><subject>Testis - metabolism</subject><subject>Testis - pathology</subject><subject>Testosterone</subject><subject>Testosterone - metabolism</subject><subject>Thiazolidinediones</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10ctKxDAUBuAgio6XhS8gATe6qObSpslSB68IutB1SZPTIUPbjElH0YX4CD6jT2J01IXgKuTw8SecH6FtSg4oIexwauoDpriUS2hEiSqzXOT5MhqRkpOMccrW0HqMU0KIUpytojVOS6IEpyP0ctRB63zQg3sADE0DZsC-wcZ3tevB4tY_YusjfA5vnJ-0btDPvgese4t9BxP9_vrGse9xnEHo9OAn0EN08QvEAYJ39nfmemydrmFwBqc34yZaaXQbYev73EB3pye34_Ps6vrsYnx0lRlecJlp0VCjqIRcNqzghampKpkxMicgNRQFGGaV1UyadLNS5rUVohRCUtBW5HwD7S1yZ8HfzyEOVeeigbbVPfh5rNKSuCgEVUWiu3_o1M9Dn36XFCu5TFskSe0vlAk-xgBNNQuu0-GpoqT6LKVKpVRfpSS78504rzuwv_KnhQQOF-DRtfD0f1J1OT5eRH4Ag7SYJA</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Hasan, Mai M.</creator><creator>El‐Shal, Amal S.</creator><creator>Mackawy, Amal M. H.</creator><creator>Ibrahim, Ebtesam M.</creator><creator>Abdelghany, Eman M. M. A.</creator><creator>Saeed, Abeer A.</creator><creator>El‐Gendy, Jehan</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2167-8841</orcidid></search><sort><creationdate>202002</creationdate><title>Ameliorative effect of combined low dose of Pioglitazone and omega‐3 on spermatogenesis and steroidogenesis in diabetic rats</title><author>Hasan, Mai M. ; El‐Shal, Amal S. ; Mackawy, Amal M. H. ; Ibrahim, Ebtesam M. ; Abdelghany, Eman M. M. A. ; Saeed, Abeer A. ; El‐Gendy, Jehan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-a6f1c918e48f2535cb1972cc840e8ae55ec2d9da28cae5d884bd6676681ead643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Androgen receptors</topic><topic>Animals</topic><topic>Antigens</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Beta cells</topic><topic>Body weight</topic><topic>Caspase</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Therapy, Combination</topic><topic>Estrogens</topic><topic>Fasting</topic><topic>Fatty Acids, Omega-3 - administration &amp; dosage</topic><topic>Fatty Acids, Omega-3 - pharmacology</topic><topic>Fertility</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Glucose</topic><topic>Glucose transporter</topic><topic>Hyperglycemia</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Immunohistochemistry</topic><topic>Infertility</topic><topic>Infertility, Male - drug therapy</topic><topic>Infertility, Male - etiology</topic><topic>Infertility, Male - metabolism</topic><topic>Infertility, Male - pathology</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Males</topic><topic>Malondialdehyde</topic><topic>Markers</topic><topic>omega‐3</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Pioglitazone</topic><topic>Pioglitazone - administration &amp; dosage</topic><topic>Pioglitazone - pharmacology</topic><topic>Polymerase chain reaction</topic><topic>PPAR</topic><topic>PPAR alpha</topic><topic>Proliferating cell nuclear antigen</topic><topic>rat male fertility</topic><topic>Rats</topic><topic>real‐time polymerase chain reaction</topic><topic>Semen</topic><topic>Semen Analysis</topic><topic>Spermatogenesis</topic><topic>Steroidogenesis</topic><topic>Subgroups</topic><topic>Superoxide dismutase</topic><topic>Testes</topic><topic>Testis - drug effects</topic><topic>Testis - metabolism</topic><topic>Testis - pathology</topic><topic>Testosterone</topic><topic>Testosterone - metabolism</topic><topic>Thiazolidinediones</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hasan, Mai M.</creatorcontrib><creatorcontrib>El‐Shal, Amal S.</creatorcontrib><creatorcontrib>Mackawy, Amal M. H.</creatorcontrib><creatorcontrib>Ibrahim, Ebtesam M.</creatorcontrib><creatorcontrib>Abdelghany, Eman M. M. A.</creatorcontrib><creatorcontrib>Saeed, Abeer A.</creatorcontrib><creatorcontrib>El‐Gendy, Jehan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hasan, Mai M.</au><au>El‐Shal, Amal S.</au><au>Mackawy, Amal M. H.</au><au>Ibrahim, Ebtesam M.</au><au>Abdelghany, Eman M. M. A.</au><au>Saeed, Abeer A.</au><au>El‐Gendy, Jehan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ameliorative effect of combined low dose of Pioglitazone and omega‐3 on spermatogenesis and steroidogenesis in diabetic rats</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J Cell Biochem</addtitle><date>2020-02</date><risdate>2020</risdate><volume>121</volume><issue>2</issue><spage>1524</spage><epage>1540</epage><pages>1524-1540</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>Background Chronic hyperglycemia is linked to either subfertility or infertility among diabetic males. Pioglitazone is one of the thiazolidinediones (TZDs) drugs that are selective peroxisome proliferator‐activated receptor (PPAR‐γ agonists used for treating type 2 diabetes mellitus (T2DM). Aim This study aims to explore the possible effect of low Pioglitazone dose and omega (ω‐3) on rat male reproductive function. Furthermore, we evaluated the add‐on effect of combined use of low Pioglitazone dose of and ω‐3 on reproductive functions in adult male T2DM rats. Methods Fifty adult male rats were included and subdivided into control and four test subgroups. T2DM was induced in test groups and subdivided into non‐treated T2DM, ω‐3 treated, 0.6 mg/kg Pioglitazone treated, and combined treated group (orally by gavage). Following 16 weeks, final body weight, testicular weight, fasting plasma glucose, and serum testosterone levels were measured. Semen analysis, testicular testosterone, malondialdehyde (MDA) concentrations, superoxide dismutase (SOD) activity, immunohistochemistry staining for apoptosis marker B‐cell lymphoma protein 2 (Bcl‐2), proliferation marker as proliferating cell nuclear antigen (PCNA), estrogen receptor α (ERα), androgen receptor (AR) were determined. Caspase‐3, nuclear factor‐kappa B (NF‐kB), glucose transporter 3 (GLUT3), 17β‐hydroxysteroid dehydrogenases (17β‐HSD) PPARγ, and PPARα genes expression were analyzed by real‐time polymerase chain reaction (RT‐PCR). Results Our findings revealed that treatment with low dose of Pioglitazone or ω‐3 significantly lowered fasting plasma glucose and MDA levels, ameliorated diabetes effects on histological damage, improved antioxidant activity (SOD), significantly improved anti‐apoptosis BCL‐2 and proliferation (PCNA), remarkably elevated ERα, AR, 17β‐HSD PPARγ, and PPARα expression with significant reduction in caspase‐3, NF‐kB genes expression and improved semen quality as well. Combined use of low dose of and ω‐3 has better effects on all measured parameters. Conclusion Small Pioglitazone dose and ω‐3 possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; while combined use of both has an add‐on effect. Combined use of low dose of and omega‐3 has better effects on all measured parameters. Thus, small dose of and omega‐3 fatty acids possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; notably use of both has an add‐on effect.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31709631</pmid><doi>10.1002/jcb.29388</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-2167-8841</orcidid></addata></record>
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1097-4644
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source MEDLINE; Access via Wiley Online Library
subjects Androgen receptors
Animals
Antigens
Antioxidants
Apoptosis
Beta cells
Body weight
Caspase
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - pathology
Dose-Response Relationship, Drug
Drug Therapy, Combination
Estrogens
Fasting
Fatty Acids, Omega-3 - administration & dosage
Fatty Acids, Omega-3 - pharmacology
Fertility
Gene expression
Genes
Glucose
Glucose transporter
Hyperglycemia
Hypoglycemic Agents - pharmacology
Immunohistochemistry
Infertility
Infertility, Male - drug therapy
Infertility, Male - etiology
Infertility, Male - metabolism
Infertility, Male - pathology
Lymphoma
Male
Males
Malondialdehyde
Markers
omega‐3
Peroxisome proliferator-activated receptors
Pioglitazone
Pioglitazone - administration & dosage
Pioglitazone - pharmacology
Polymerase chain reaction
PPAR
PPAR alpha
Proliferating cell nuclear antigen
rat male fertility
Rats
real‐time polymerase chain reaction
Semen
Semen Analysis
Spermatogenesis
Steroidogenesis
Subgroups
Superoxide dismutase
Testes
Testis - drug effects
Testis - metabolism
Testis - pathology
Testosterone
Testosterone - metabolism
Thiazolidinediones
title Ameliorative effect of combined low dose of Pioglitazone and omega‐3 on spermatogenesis and steroidogenesis in diabetic rats
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