Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice

Abstract Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study exp...

Full description

Bibliographic Details
Main Authors: Wenjing Zhang, Zhenhua Tian, Xiangyu Qi, Pengcheng Chen, Qian Yang, Qingbo Guan, Jifeng Ye, Chunxiao Yu
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-41291-2
_version_ 1797560150313140224
author Wenjing Zhang
Zhenhua Tian
Xiangyu Qi
Pengcheng Chen
Qian Yang
Qingbo Guan
Jifeng Ye
Chunxiao Yu
author_facet Wenjing Zhang
Zhenhua Tian
Xiangyu Qi
Pengcheng Chen
Qian Yang
Qingbo Guan
Jifeng Ye
Chunxiao Yu
author_sort Wenjing Zhang
collection DOAJ
description Abstract Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.
first_indexed 2024-03-10T17:55:22Z
format Article
id doaj.art-db69ff3a32c9457197a2f63a4bcdde49
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-03-10T17:55:22Z
publishDate 2023-08-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-db69ff3a32c9457197a2f63a4bcdde492023-11-20T09:13:20ZengNature PortfolioScientific Reports2045-23222023-08-0113111310.1038/s41598-023-41291-2Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male miceWenjing Zhang0Zhenhua Tian1Xiangyu Qi2Pengcheng Chen3Qian Yang4Qingbo Guan5Jifeng Ye6Chunxiao Yu7Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, Shandong UniversityAbstract Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.https://doi.org/10.1038/s41598-023-41291-2
spellingShingle Wenjing Zhang
Zhenhua Tian
Xiangyu Qi
Pengcheng Chen
Qian Yang
Qingbo Guan
Jifeng Ye
Chunxiao Yu
Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice
Scientific Reports
title Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice
title_full Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice
title_fullStr Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice
title_full_unstemmed Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice
title_short Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice
title_sort switching from high fat diet to normal diet ameliorate btb integrity and improve fertility potential in obese male mice
url https://doi.org/10.1038/s41598-023-41291-2
work_keys_str_mv AT wenjingzhang switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice
AT zhenhuatian switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice
AT xiangyuqi switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice
AT pengchengchen switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice
AT qianyang switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice
AT qingboguan switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice
AT jifengye switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice
AT chunxiaoyu switchingfromhighfatdiettonormaldietamelioratebtbintegrityandimprovefertilitypotentialinobesemalemice