Active vitamin D deficiency mediated by extracellular calcium and phosphorus results in male infertility in young mice

2015 ◽  
Vol 308 (1) ◽  
pp. E51-E62 ◽  
Author(s):  
Weiwei Sun ◽  
Lulu Chen ◽  
Wei Zhang ◽  
Rong Wang ◽  
David Goltzman ◽  
...  
Keyword(s):  
Vitamin D ◽  
Male Infertility ◽  
Sperm Count ◽  
Normal Diet ◽  
Extracellular Calcium ◽  
Spermatogenic Cells ◽  
Wild Type ◽  
Hypergonadotropic Hypogonadism ◽  
Active Vitamin ◽  
Calcium And Phosphorus

We used mice with targeted deletion of 25-hydroxyvitamin D-1 α-hydroxylase [1α(OH)ase−/−] to investigate whether 1,25(OH)2D3 deficiency results in male infertility mediated by 1,25(OH)2D3 or extracellular calcium and phosphorus. Male 1α(OH)ase−/− and their wild-type littermates fed either a normal diet or a rescue diet from weaning were mated at 6–14 wk of age with female wild-type mice on the same diet. The fertility efficiency of females was analyzed, and the reproductive phenotypes of males were evaluated by histopathological and molecular techniques. Hypocalcemic and hypophosphatemic male 1α(OH)ase−/− mice on a normal diet developed infertility characterized by hypergonadotropic hypogonadism, with downregulation of testicular calcium channels, lower intracellular calcium levels, decreased sperm count and motility, and histological abnormalities of the testes. The proliferation of spermatogenic cells was decreased with downregulation of cyclin E and CDK2 and upregulation of p53 and p21 expression, whereas apoptosis of spermatogenic cells was increased with upregulation of Bax and p-caspase 3 expression and downregulation of Bcl-xl expression. When serum calcium and phosphorus were normalized by the rescue diet, the defective reproductive phenotype in the male 1α(OH)ase−/− mice, including the hypergonadotropic hypogonadism, decreased sperm count and motility, histological abnormalities of testis, and defective spermatogenesis, was reversed. These results indicate that the infertility seen in male 1,25(OH)2D3-deficient mice is not a direct effect of active vitamin D deficiency on the reproductive system but is an indirect effect mediated by extracellular calcium and phosphorus.

scholarly journals Vitamin D Is an Important Factor in Estrogen Biosynthesis of Both Female and Male Gonads*

Endocrinology ◽  
2000 ◽  
Vol 141 (4) ◽  
pp. 1317-1324 ◽  
Author(s):  
Keiko Kinuta ◽  
Hiroyuki Tanaka ◽  
Tadashi Moriwake ◽  
Kunihiko Aya ◽  
Shigeaki Kato ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sperm Count ◽  
Calcium Supplementation ◽  
Elevated Serum ◽  
Aromatase Activity ◽  
Wild Type ◽  
Gene Expressions ◽  
Estrogen Synthesis ◽  
Histological Abnormality ◽  
Estrogen Biosynthesis

Abstract In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor α and β were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.

scholarly journals Skin Inflammation and Testicular Function: Dermatitis Causes Male Infertility via Skin-Derived Cytokines

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 293
Author(s):  
Ai Umaoka ◽  
Hiroki Takeuchi ◽  
Kento Mizutani ◽  
Naohiro Seo ◽  
Yoshiaki Matsushima ◽  
...  
Keyword(s):  
Mouse Model ◽  
Male Infertility ◽  
Inflammatory Cytokines ◽  
Sperm Count ◽  
Skin Inflammation ◽  
Testicular Function ◽  
Testis Size ◽  
Sperm Viability ◽  
Wild Type ◽  
The Relationship

The medical comorbidities including skin diseases are associated with male infertility. The most common cause of male infertility is the inability of testes to produce sperm; however, the influence of persistent dermatitis on testicular function has not been elucidated so far. We investigated the relationship between skin inflammation and impaired sperm production using a spontaneous dermatitis mouse model. We examined the breeding records of dermatitis mice and their wild-type littermates. Sperm count, motility, and viability were analyzed by direct microscopic observation and flow cytometry. In addition, testis and epididymis were histologically examined. Finally, sperm viability was evaluated in another dermatitis mouse model and in wild-type mice in which inflammatory cytokines were intraperitoneally administered. Compared to wild-type littermate mice, the number of children born was lower in mice with dermatitis. The body weight and testis size were decreased age-dependently. In the skin disease group, the sperm count and movement ratio were clearly decreased, and reduced sperm viability was observed. Histological examination revealed the detachment of Sertoli cells and reduced spermatogenesis. The fibrosis of epididymal stroma was severe, and it might affect defective sperm maturation in the epididymis. In addition, this phenomena was reproduced by a hapten applied dermatitis mouse model and the intraperitoneal administration of inflammatory cytokines. Once the skin is inflamed, inflammatory cytokines are produced and released, which may affect testicular and sperm function. Additional studies are needed to determine the relationship between male infertility and severe dermatitis in human.

scholarly journals No Role of Osteocytic Osteolysis in the Development and Recovery of the Bone Phenotype Induced by Severe Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 7989
Author(s):  
Barbara M. Misof ◽  
Stéphane Blouin ◽  
Jochen G. Hofstaetter ◽  
Paul Roschger ◽  
Jochen Zwerina ◽  
...  
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Bone Mineralization ◽  
Normal Diet ◽  
Wild Type ◽  
Mineral Homeostasis ◽  
Osteocyte Lacunae ◽  
Osteocytic Osteolysis ◽  
Electron Imaging

Osteocytic osteolysis/perilacunar remodeling is thought to contribute to the maintenance of mineral homeostasis. Here, we utilized a reversible, adult-onset model of secondary hyperparathyroidism to study femoral bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging. Male mice with a non-functioning vitamin D receptor (VDRΔ/Δ) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD). Thereafter, VDRΔ/Δ mice received either the CD, a normal diet (ND), or the RD. At baseline, BMDD and OLS characteristics were similar in VDRΔ/Δ and wild-type mice. The CD induced large cortical pores, osteomalacia, and a reduced epiphyseal average degree of mineralization in the VDRΔ/Δ mice relative to the baseline (−9.5%, p < 0.05 after two months and −10.3%, p < 0.01 after five months of the CD). Switching VDRΔ/Δ mice on the CD back to the RD fully restored BMDD to baseline values. However, OLS remained unchanged in all groups of mice, independent of diet. We conclude that adult VDRΔ/Δ animals on an RD lack any skeletal abnormalities, suggesting that VDR signaling is dispensable for normal bone mineralization as long as mineral homeostasis is normal. Our findings also indicate that VDRΔ/Δ mice attempt to correct a calcium challenge by enhanced osteoclastic resorption rather than by osteocytic osteolysis.

Vitamin D Deficiency and Intoxication - A concern either way

JMS SKIMS ◽  
2011 ◽  
Vol 14 (2) ◽  
pp. 40-42
Author(s):  
Muzafar Maqsood Wani ◽  
Imtiaz Ahmed Wani
Keyword(s):  
Vitamin D ◽  
Cell Growth ◽  
Bone Turnover ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Deficiency ◽  
Bone Mineralization ◽  
Normal Blood ◽  
Blood Levels ◽  
Calcium And Phosphorus ◽  
Biologic Function

Major biologic function of activated vitamin D is to maintain normal blood levels of calcium and phosphorus, thus regulating bone mineralization. Research suggests that vitamin D may help in immunomodulation, regulating cell growth and 1,4 differentiation as well as some diverse unspecified functions. Overt vitamin D deficiency leads to hypocalcaemia, secondary hyperparathyroidism and increased bone turnover, which in prolonged and severe cases may cause rickets in children and osteomalacia in elderly.... JMS 2011;14(2):40-42

The Protective Effect of Metformin against Oxandrolone-Induced Infertility in Male Rats

2020 ◽  
Vol 26 ◽  
Author(s):  
Abdulqader Fadhil Abed ◽  
Yazun Bashir Jarrar ◽  
Hamzeh J Al-Ameer ◽  
Wajdy Al-Awaida ◽  
Su-Jun Lee
Keyword(s):  
Gene Expression ◽  
Male Infertility ◽  
Protective Effect ◽  
Histological Examination ◽  
Sperm Count ◽  
Serum Testosterone ◽  
Male Rats ◽  
P Value ◽  
Protective Effects ◽  
Rt Pcr

Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05). Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.

Distinct Modulation of Wild-Type and Selective Gene Mutated Vitamin D Receptor by Essential Poly Unsaturated Fatty Acids

2021 ◽  
Vol 21 ◽  
Author(s):  
Hari Balaji ◽  
Selvaraj Ayyamperuma ◽  
Niladri Saha ◽  
Shyam Sundar Pottabathula ◽  
Jubie Selvaraj ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Vitamin D ◽  
Ligand Binding ◽  
Vitamin D Deficiency ◽  
Binding Affinity ◽  
Unsaturated Fatty Acids ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Binding Energies ◽  
Wild Type

: Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor’s (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of evidence report that selective long chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to transcriptional activation. We therefore hypothesize that selective PUFAs would modulate the dynamics and kinetics of VDRs, irrespective bioactive of vitamin-D binding. The spatial arrangements of the selected PUFAs in VDR active site were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR (PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.

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