Fatemeh Dehghan Shahreza1, Mehdi Hajian2, Parvis Gharagozloo3, Joël R Drevet4, Mohammad Hossein Nasr-Esfahani2. 1. Department of Clinical Science, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran. 2. Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. 3. CellOxess LLC, Ewing, NJ, USA. 4. GReD Laboratory, Faculty of Medicine, CNRS UMR6293-INSERM U1103-Univesité Clermont Auvergne, Clermont-Ferrand, France.
Abstract
BACKGROUND: In rodents and humans, vitamin D deficiency (VDD) is associated with altered sperm structure and function (primarily decreased motility and morphological abnormalities) that are primarily attributed to VDD-induced hypocalcemia. However, it is suspected that VDD has much more drastic effects on mammalian spermatozoa. OBJECTIVES: The purpose of this study was to illustrate that VDD, depending on its severity and duration, can alter sperm nuclear integrity and can also lead to the loss of spermatozoa's ability to support embryonic development. MATERIALS AND METHODS: A mouse model of induced VDD combining the action of a vitamin D-deficient diet, UV exposure limitation, and paricalcitol injections; a vitamin D2 analog that catabolizes endogenous vitamin D by increasing the expression of CYP24A, a member of the cytochrome P450 family, has been used to create different grades of VDD. RESULTS: We show that the most significant sperm defect recorded concerns the integrity of the paternal nucleus, which is both decondensed and fragmented in moderate-to-severe VDD situations. Consistent with the known consequences of fertilization with DNA-damaged spermatozoa, we show that paternal VDD decreases the ability of spermatozoa to optimally support fertilization and embryonic development. DISCUSSION AND CONCLUSION: Given the worldwide high prevalence of VDD in humans, and although obtained in an animal model, the data presented here suggest that subfertile/infertile males may benefit from VDD testing and that attempts to correct serum vitamin D levels could be considered prior to conception, either naturally or through ART.
BACKGROUND: In rodents and humans, vitamin D deficiency (VDD) is associated with altered sperm structure and function (primarily decreased motility and morphological abnormalities) that are primarily attributed to VDD-induced hypocalcemia. However, it is suspected that VDD has much more drastic effects on mammalian spermatozoa. OBJECTIVES: The purpose of this study was to illustrate that VDD, depending on its severity and duration, can alter sperm nuclear integrity and can also lead to the loss of spermatozoa's ability to support embryonic development. MATERIALS AND METHODS: A mouse model of induced VDD combining the action of a vitamin D-deficient diet, UV exposure limitation, and paricalcitol injections; a vitamin D2 analog that catabolizes endogenous vitamin D by increasing the expression of CYP24A, a member of the cytochrome P450 family, has been used to create different grades of VDD. RESULTS: We show that the most significant sperm defect recorded concerns the integrity of the paternal nucleus, which is both decondensed and fragmented in moderate-to-severe VDD situations. Consistent with the known consequences of fertilization with DNA-damaged spermatozoa, we show that paternal VDD decreases the ability of spermatozoa to optimally support fertilization and embryonic development. DISCUSSION AND CONCLUSION: Given the worldwide high prevalence of VDD in humans, and although obtained in an animal model, the data presented here suggest that subfertile/infertile males may benefit from VDD testing and that attempts to correct serum vitamin D levels could be considered prior to conception, either naturally or through ART.