title: Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier.
abstract: Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD) for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB) integrity may be one of the crucial underlying factors accounting for this change.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Reproductive Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Reproductive Medicine, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Reproductive Medicine, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xue
authors.affiliation: Department of Medical Laboratory Science, The Central Hospital of Zhabei District, Shanghai, China.
authors.forename: Guobao
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Reproductive Medicine, Shanghai, China; Department of Human Reproductive Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Reproductive Medicine, Shanghai, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Reproductive Medicine, Shanghai, China.
authors.forename: Zhide
authors.initials: Z
authors.lastname: Ding
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000473:pathology*; D001835:Body Weight; D002966:Clathrin / Q000378:metabolism; D059305:Diet, High-Fat; D004958:Estradiol / Q000032:analysis; D005260:Female; D005298:Fertility / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009765:Obesity / Q000209:etiology*; D062793:Occludin / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013081:Sperm Motility; D013094:Spermatozoa / Q000502:physiology; D013737:Testis / Q000098:blood supply / Q000473:pathology*; D013739:Testosterone / Q000032:analysis; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D002966:Clathrin; D008055:Lipids; D062793:Occludin; D011944:Receptors, Androgen; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D013739:Testosterone; D004958:Estradiol