• PMID: 28911169
• Gene Name: CRISP4
• Condition: Sperm fertilization capacity, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Sperm fertilization capacity, Male infertility

Obesity-Induced Infertility in Male Mice Is Associated With Disruption of Crisp4 Expression and Sperm Fertilization Capacity

Borges BC, Garcia-Galiano D, da Silveira Cruz-Machado S, Han X, Gavrilina GB, Saunders TL, Auchus RJ, Hammoud SS, Smith GD, Elias CF.

Approximately 15% of human couples of reproductive age have impaired fertility, and the male component accounts for about half of these cases. The etiology is usually unknown, but high correlation with the increase in obesity rates is documented. In this study, we show that diet-induced and genetically obese mice display copulatory behavior comparable to controls, but the number of females impregnated by obese males is remarkably low. Screening for changes in gene expression in the male reproductive tract showed decreased Crisp4 expression in testis and epididymis of obese mice. Lack of CRISP4 in the luminal membrane of epididymal cells indicated inadequate secretion. Consistent with CRISP4 action in acrosome reaction, sperm from mice fed a high-fat diet (HFD) had decreased fertilization capacity. CRISP4 treatment of sperm from HFD mice prior to in vitro fertilization improved fertilization rate. In leptin-deficient obese and infertile mice, leptin's effect to restore CRISP4 expression and function required gonadal hormones. Our findings indicate that the obesity-induced decline in sperm motility and fertilization capacity results in part from the disruption of epididymal CRISP4 expression and secretion. CI - Copyright © 2017 Endocrine Society. FAU - Borges, Beatriz C AU - Borges BC AD - Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109. FAU - Garcia-Galiano, David AU - Garcia-Galiano D AD - Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109. FAU - da Silveira Cruz-Machado, Sanseray AU - da Silveira Cruz-Machado S AD - Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109. AD - Department of Physiology, University of São Paulo, São Paulo 05508-900, SP-Brazil. FAU - Han, Xingfa AU - Han X AD - Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109. AD - Isotope Research Laboratory, Sichuan Agricultural University, Ya'an 625014, People's Republic of China. FAU - Gavrilina, Galina B AU - Gavrilina GB AD - University of Michigan Transgenic Animal Model Core, Ann Arbor, Michigan 48109. FAU - Saunders, Thomas L AU - Saunders TL AD - University of Michigan Transgenic Animal Model Core, Ann Arbor, Michigan 48109. AD - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109. FAU - Auchus, Richard J AU - Auchus RJ AD - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109. AD - Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109. FAU - Hammoud, Saher S AU - Hammoud SS AD - Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109. FAU - Smith, Gary D AU - Smith GD AD - Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109. AD - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan 48109. AD - Department of Urology, University of Michigan, Ann Arbor, Michigan 48109.