Cover Image

Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik

Excessive levels of leptin have a detrimental effect on the male reproductive system eventually leading to infertility. However, is still unclear how these effects are brought about. Several different signaling pathways are involved in mediating leptin's effects. One of these pathways is the AM...

Full description

Saved in:
Bibliographic Details
Main Author: Alam Malik, Ifrah
Format: Thesis
Language:English
Published: 2023
Subjects:
Urinary and Reproductive Organs
Reproduction. Physiology of sex
Online Access:https://ir.uitm.edu.my/id/eprint/109978/1/109978.PDF
https://ir.uitm.edu.my/id/eprint/109978/
Tags: Add Tag
No Tags, Be the first to tag this record!
id my.uitm.ir.109978
record_format eprints
institution Universiti Teknologi Mara
building Tun Abdul Razak Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Teknologi Mara
content_source UiTM Institutional Repository
url_provider http://ir.uitm.edu.my/
language English
topic Urinary and Reproductive Organs
Reproduction. Physiology of sex
spellingShingle Urinary and Reproductive Organs
Reproduction. Physiology of sex
Alam Malik, Ifrah
Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik
description Excessive levels of leptin have a detrimental effect on the male reproductive system eventually leading to infertility. However, is still unclear how these effects are brought about. Several different signaling pathways are involved in mediating leptin's effects. One of these pathways is the AMPK pathway. Therefore, to understand if the AMPK pathway is involved in mediating leptin's adverse effects, Dorsomorphin was used to inhibit the AMPK pathway and observe if that would lead to any decrease or inhibition of the effects of leptin on sperm and testicular tissue in Sprague-Dawley rats. Furthermore, leptin causes these adverse effects by inducing oxidative stress. Therefore, Profortil®, a concoction of several different antioxidants, was administered to leptin­ treated rats to observe if it could prevent the adverse effects of leptin in the male reproductive system of Sprague-Dawley rats. In study I, adult male Sprague-Dawley rats were divided into three groups: Control, which was given O.lml normal saline. Leptin, which was treated with 60µg/kg/day ofleptin, and leptin+Dorsomorphin which was concurrently treated with leptin and Dorsomorphin at 5mg/kg/day. Treatments were given for 2 weeks via the intraperitoneal route. Food intake and body weight of the rats was measured weekly. At the end of the treatment, the rats were euthanized, and testes and epididymides were collected to measure the organ weight, total sperm count, percentage of sperm with abnormal morphology, ST diameter and epithelial height, expression of connexin-43 and occludin, concentration of 8-OHdG, testosterone, inhibin B, Acetyl-CcA carboxylase and phosphorylated AMPK. In study II, adult Sprague-Dawley rats were divided into 4 groups: Control, which was given O. lrnl normal saline. Leptin, which was administered 60µg/kg/day leptin for 2 weeks. Leptin+Profortil, which was given leptin and Profortil at 50 mg/kg/day. Profortil was given initially for 1 week, followed by another two weeks concurrently with leptin. The last group received only Profortil at 50mg/kg/day for 3 weeks. Normal saline and leptin were given via the intraperitoneal route. Profortil was given by oral gavage. Food intake and body weight of the rats was measured weekly. At the end of the treatment, sperm and testes were collected to measure the organ weight, total sperm count, percentage of sperm with abnormal morphology, concentration of testosterone, CYPl 7al, CYP19al, 17β-HSD, total antioxidant capacity, 8-OHdG, SOD and catalase activity, gene expression of catalase, concentration of phosphorylated AKT and PIP3, testicular cell apoptosis and sperm DNA fragmentation. Results from study I showed that leptin administration caused a decrease in total sperm count, increase in percentage of sperm with abnormal morphology, decrease in ST epithelial height, increase in concentration of 8-0HdG and decrease in gene expression of occludin and connexin-43 in the testicular tissue. Dorsomorphin administration in the leptin-induced rats did not have any significant effect on any of the parameters that were affected by leptin administration. In study II, leptin administration caused a decrease in total sperm count, increase in fraction of sperm with abnormal morphology, increased 8-OHdG concentration, decrease in catalase activity and gene expression, decreased gene expression of connexin-43 and occludin, increased testicular cell apoptosis and sperm DNA fragmentation. Treatment with Profortil prevented the effect ofleptin on the total sperm count. However, no other effects of Profortil were observed on the rest of the leptin-induced parameters measured. The results from study I indicate that perhaps the AMPK pathway may not be involved in mediating the adverse effects of leptin on the sperm and testes in the Sprague-Dawley rats. The results from study II indicate that Profortil administration was able to alleviate some effects of leptin on the male reproductive system but not all.
format Thesis
author Alam Malik, Ifrah
author_facet Alam Malik, Ifrah
author_sort Alam Malik, Ifrah
title Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik
title_short Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik
title_full Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik
title_fullStr Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik
title_full_unstemmed Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik
title_sort leptin-induced changes in the male reproductive system: role of ampk pathway and effects of profortil / ifrah alam malik
publishDate 2023
url https://ir.uitm.edu.my/id/eprint/109978/1/109978.PDF
https://ir.uitm.edu.my/id/eprint/109978/
_version_ 1825165140184530944
spelling my.uitm.ir.1099782025-02-12T02:50:02Z https://ir.uitm.edu.my/id/eprint/109978/ Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik Alam Malik, Ifrah Urinary and Reproductive Organs Reproduction. Physiology of sex Excessive levels of leptin have a detrimental effect on the male reproductive system eventually leading to infertility. However, is still unclear how these effects are brought about. Several different signaling pathways are involved in mediating leptin's effects. One of these pathways is the AMPK pathway. Therefore, to understand if the AMPK pathway is involved in mediating leptin's adverse effects, Dorsomorphin was used to inhibit the AMPK pathway and observe if that would lead to any decrease or inhibition of the effects of leptin on sperm and testicular tissue in Sprague-Dawley rats. Furthermore, leptin causes these adverse effects by inducing oxidative stress. Therefore, Profortil®, a concoction of several different antioxidants, was administered to leptin­ treated rats to observe if it could prevent the adverse effects of leptin in the male reproductive system of Sprague-Dawley rats. In study I, adult male Sprague-Dawley rats were divided into three groups: Control, which was given O.lml normal saline. Leptin, which was treated with 60µg/kg/day ofleptin, and leptin+Dorsomorphin which was concurrently treated with leptin and Dorsomorphin at 5mg/kg/day. Treatments were given for 2 weeks via the intraperitoneal route. Food intake and body weight of the rats was measured weekly. At the end of the treatment, the rats were euthanized, and testes and epididymides were collected to measure the organ weight, total sperm count, percentage of sperm with abnormal morphology, ST diameter and epithelial height, expression of connexin-43 and occludin, concentration of 8-OHdG, testosterone, inhibin B, Acetyl-CcA carboxylase and phosphorylated AMPK. In study II, adult Sprague-Dawley rats were divided into 4 groups: Control, which was given O. lrnl normal saline. Leptin, which was administered 60µg/kg/day leptin for 2 weeks. Leptin+Profortil, which was given leptin and Profortil at 50 mg/kg/day. Profortil was given initially for 1 week, followed by another two weeks concurrently with leptin. The last group received only Profortil at 50mg/kg/day for 3 weeks. Normal saline and leptin were given via the intraperitoneal route. Profortil was given by oral gavage. Food intake and body weight of the rats was measured weekly. At the end of the treatment, sperm and testes were collected to measure the organ weight, total sperm count, percentage of sperm with abnormal morphology, concentration of testosterone, CYPl 7al, CYP19al, 17β-HSD, total antioxidant capacity, 8-OHdG, SOD and catalase activity, gene expression of catalase, concentration of phosphorylated AKT and PIP3, testicular cell apoptosis and sperm DNA fragmentation. Results from study I showed that leptin administration caused a decrease in total sperm count, increase in percentage of sperm with abnormal morphology, decrease in ST epithelial height, increase in concentration of 8-0HdG and decrease in gene expression of occludin and connexin-43 in the testicular tissue. Dorsomorphin administration in the leptin-induced rats did not have any significant effect on any of the parameters that were affected by leptin administration. In study II, leptin administration caused a decrease in total sperm count, increase in fraction of sperm with abnormal morphology, increased 8-OHdG concentration, decrease in catalase activity and gene expression, decreased gene expression of connexin-43 and occludin, increased testicular cell apoptosis and sperm DNA fragmentation. Treatment with Profortil prevented the effect ofleptin on the total sperm count. However, no other effects of Profortil were observed on the rest of the leptin-induced parameters measured. The results from study I indicate that perhaps the AMPK pathway may not be involved in mediating the adverse effects of leptin on the sperm and testes in the Sprague-Dawley rats. The results from study II indicate that Profortil administration was able to alleviate some effects of leptin on the male reproductive system but not all. 2023 Thesis NonPeerReviewed text en https://ir.uitm.edu.my/id/eprint/109978/1/109978.PDF Leptin-induced changes in the male reproductive system: role of AMPK pathway and effects of Profortil / Ifrah Alam Malik. (2023) PhD thesis, thesis, Universiti Teknologi MARA (Kampus Sg. Buloh). <http://terminalib.uitm.edu.my/109978.pdf>
score 13.239859

Similar Items