Restoring Impaired Fertility Through Diet: Observations of Switching From High-Fat Diet During Puberty to Normal Diet in Adulthood Among Obese Male Mice

Abstract

BackgroundObesity is associated with a decrease in testicular function, yet the effects and mechanisms relative to different stages of sexual development remain unclear. The aim of this study is to determine whether high-fat diet-induced obesity impairs male fertility during puberty and in adulthood, and to ascertain its underlying mechanisms. This study aims to further reveal whether restoring to a normal diet can improve impaired fertility.MethodsMale mice were divided into 6 groups: the group N and H exposed to a normal diet or high-fat diet during puberty. The group NN or NH were further maintained a normal diet or exposed to high-fat diet in adulthood, the group HH or HN were further maintained high-fat diet or switched to normal diet in adulthood. Metabolic parameters, fertility parameters, testicular function parameters, TUNEL staining and testicular function-related proteins were evaluated, respectively.ResultsThe fertility of the mice in the high-fat diet group was impaired, which validated by declines in pregnancy rates and litter weight loss. Further analysis demonstrated the increased level of oxidative stress, the increased number of spermatogenic cell apoptosis and decreased number of sperm and decreased acrosome integrity. The expression of steroidogenic acute regulatory (StAR) and spermatogenesis related proteins (WT-1) decreased. Fertility among the HN group recovered, accompanied by the recovery of metabolism, fertility and testicular function parameters, StAR and WT-1 expression.ConclusionsThe findings suggest that high-fat diet-induced obesity impairs male fertility during puberty and in adulthood. The loss of acrosome integrity, the increase of oxidative stress, the increase of cells apoptosis and the down-regulation of StAR and WT-1 may be the underlying mechanisms. Switching from high-fat diets during puberty to normal diets in adulthood can improve male fertility.

Obesity, sexual maturation and male reproduction

“…Although obesity alters hormone levels, direct effects on testicular morphophysiology and spermatogenesis also occur (KORT et al, 2006;HAMMOUD et al, 2008;DAVIDSON ET AL., 2015;LEISEGANG et al, 2021;QI et al, 2022). Atrophy of the seminiferous epithelium and changes in the integrity and increased permeability of the hematotesticular barrier were evidenced in mice fed a high-fat diet for 10 weeks (FAN et al, 2015).…”

The time-dependent adverse effects of a high-fat diet on sperm parameters

“…The testes were rapidly preserved in liquid nitrogen for Oil Red O staining and protein analysis, or in modified Davidson's fluid (mDF) for morphological analysis. 21,22…”

“…The serum levels of glucose (GLU), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were evaluated using Mindray Automatic biochemical analyzer BS-830 (Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China). 21,22…”

“…Subsequently, 10 µL of diluted sperm suspension (1:20) was transferred to a sperm counting plate of the computer-assisted semen analyzer (CASA) IVOS II (Hamilton-Thorne Bioscience, Beverly, USA) for the automated analysis. 22 This analysis included sperm concentration and progressive and nonprogressive motility, as well as characterizing movement as rapid, moderate or static. Sperm velocity was also assessed, including average path velocity (VAP), linear velocity (VSL) and curvilinear velocity (VCL).…”

“…Sections were deparaffinized, rehydrated, stained with hematoxylin and eosin (H&E), and then scanned with the Aperio VERSA light microscopy scanning system (Leica Biosystems, Richmond, USA). 22 Damage to seminiferous tubules and spermatogenesis were evaluated according to the Cosentino's scoring system: 1. Normal testicular architecture with an orderly arrangement of germinal cells; 2.…”