Association between 25(OH)-vitamin D and testosterone levels: Evidence from men with chronic spinal cord injury.

OBJECTIVE: As an independent linear association between 25-hydroxyvitamin D (25(OH)D) and testosterone levels is controversial, this study aimed to explore this topic in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of both androgen and vitamin D deficiency. DESIGN: Forty-nine men with chronic SCI consecutively admitted to a rehabilitation program underwent clinical/biochemical evaluations. RESULTS: Deficiency of 25(OH)D (<20 ng/mL) was found in 36 patients (73.5%). They exhibited significantly lower total testosterone and free testosterone levels, higher parathyroid hormone (PTH) and HOMA-IR, a poorer functional independence degree, and were engaged in poorer weekly leisure time physical activity (LTPA). Significant correlates of 25(OH)D levels were: total testosterone, free testosterone, PTH, functional independence degree and weekly LTPA. At the linear regression models, lower 25(OH)D levels were associated with both lower total and free testosterone after adjustment for age, smoking, alcohol consumption, comorbidities and HOMA-IR. However, after full adjustment, also including functional independence degree, BMI and LTPA, only the association of lower 25(OH)D with lower free testosterone was still significant. CONCLUSION: In men with SCI, 25(OH)D correlates with total and free testosterone and exhibits an independent linear association with free testosterone. Regardless of this independent link, hypovitaminosis D and androgen deficiency are markers of poor health, sharing common risk factors to take into account in the rehabilitative approach to patients with SCI.

Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) has been claimed as a liver phenotype of metabolic syndrome, which in turn is associated with male hypogonadism. We assessed whether an independent association between NAFLD and androgen deficiency could be revealed in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of biochemical androgen deficiency and a combination of risk factors for metabolic syndrome. DESIGN: Fifty-five consecutive men with chronic SCI admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography. RESULTS: NAFLD was diagnosed in 27 patients (49.1%). Men with NAFLD were older and exhibited significantly higher body mass index, Homeostatic model assessment of insulin resistance, triglycerides and gamma-glutamyl transpeptidase values, lower total and free testosterone levels and they were engaged in a significantly poorer weekly leisure time physical activity (LTPA). At the multiple logistic regression analysis, only total and free testosterone levels exhibited a significant independent association with NAFLD. The risk of having NAFLD increased indeed of 1% for each decrement of 1 ng/dL of total testosterone and of 3% for each decrement of 1 pg/mL of free testosterone, after adjustment for confounders. In men with total testosterone < 300 ng/dL (36.4%) the prevalence of NAFLD reached 85%: they had a risk of having NAFLD significantly higher (∼12-fold) than those with total testosterone ≥ 300 ng/dL, after adjustment for confounders. CONCLUSION: The evidence of an independent association between NAFLD and low testosterone is strongly reinforced by its demonstration in men with chronic SCI, in spite of the many confounders peculiar to this population.

Soluble products of Escherichia coli induce mitochondrial dysfunction-related sperm membrane lipid peroxidation which is prevented by lactobacilli.

Unidentified soluble factors secreted by E. coli, a frequently isolated microorganism in genitourinary infections, have been reported to inhibit mitochondrial membrane potential (ΔΨm), motility and vitality of human spermatozoa. Here we explore the mechanisms involved in the adverse impact of E. coli on sperm motility, focusing mainly on sperm mitochondrial function and possible membrane damage induced by mitochondrial-generated reactive oxygen species (ROS). Furthermore, as lactobacilli, which dominate the vaginal ecosystem of healthy women, have been shown to exert anti-oxidant protective effects on spermatozoa, we also evaluated whether soluble products from these microorganisms could protect spermatozoa against the effects of E. coli. We assessed motility (by computer-aided semen analysis), ΔΨm (with JC-1 dye by flow cytometry), mitochondrial ROS generation (with MitoSOX red dye by flow cytometry) and membrane lipid-peroxidation (with the fluorophore BODIPY C11 by flow cytometry) of sperm suspensions exposed to E. coli in the presence and in the absence of a combination of 3 selected strains of lactobacilli (L. brevis, L. salivarius, L. plantarum). A Transwell system was used to avoid direct contact between spermatozoa and microorganisms. Soluble products of E. coli induced ΔΨm loss, mitochondrial generation of ROS and membrane lipid-peroxidation, resulting in motility loss. Soluble factors of lactobacilli prevented membrane lipid-peroxidation of E. coli-exposed spermatozoa, thus preserving their motility. In conclusion, sperm motility loss by soluble products of E. coli reflects a mitochondrial dysfunction-related membrane lipid-peroxidation. Lactobacilli could protect spermatozoa in the presence of vaginal disorders, by preventing ROS-induced membrane damage.

Effect of vaginal probiotic lactobacilli on in vitro-induced sperm lipid peroxidation and its impact on sperm motility and viability.

A combination of three selected strains of lactobacilli (Lactobacillus brevis [CD2], L. salivarius [FV2], and L. plantarum [FV9]), whose effectiveness in treating bacterial vaginosis in the form of vaginal tablets has been reported recently, prevented sperm lipid peroxidation that was induced in vitro by a ferrous ion promoter, thus preserving sperm motility and viability. This finding suggests the potential of vaginal probiotic lactobacilli for protecting human spermatozoa from radical oxygen species in the presence of vaginal disorders, thereby improving the fertilization potential of the female host.

Protein tyrosine phosphorylation of the human sperm head during capacitation: immunolocalization and relationship with acquisition of sperm-fertilizing ability.

The occurrence of tyrosine phosphorylation (TP) in the sperm head during capacitation has been poorly investigated, and no data exist on the relationship of its dynamics with the acquisition of sperm fertilizing ability. This study localized TP of head proteins in human spermatozoa during capacitation and explored its relationship with acquisition of the ability to display progesterone (P)-stimulated acrosome reactions (ARs) and to penetrate zona-free hamster oocytes. By immunofluorescence, TP immunoreactivity was revealed in the acrosomal region of formaldehyde-fixed/unpermeabilized samples, whereas it was abolished in fixed/permeabilized samples, in which TP immunoreactivity was high in the principal piece. No TP immunoreactivity was detectable in unfixed spermatozoa. Head TP immunoreactivity was localized externally to the acrosome, close to the cytoplasmic membrane, as assessed by transmission electron microscopy. The increase in head TP was an early event during capacitation, occurring within 1 h in capacitating conditions. At this time, the P-stimulated ARs were also increased, whereas egg penetration was as poor as in uncapacitated spermatozoa. At 5 h of capacitation, the extent of neither head TP nor the P-induced ARs were greater than that at 1 h, whereas egg penetration had significantly increased. Seminal plasma inhibited head TP, P-induced ARs and egg penetration. None of these inhibitory effects, unlike those on tail TP, were prevented by the cAMP analogue dbcAMP (N,2-O-dibutyryladenosine 3',5'-cyclic monophosphate). In conclusion, head TP is a subsurface event occurring early during capacitation and is closely related to acquisition of the ability to display P-stimulated ARs, whereas the ability to fuse with oolemma and to decondense is a later capacitation-related event.

Retinol binding protein 4, low birth weight-related insulin resistance and hormonal contraception.

It has been recently reported that increased serum levels of retinol binding protein 4 (RBP4), a molecule secreted by adipocytes and liver, could be an early marker of insulin resistance (IR). We determined whether serum RBP4 was increased in low birth weight (LBW)-young women as a model of early-onset IR, through a historical prospective study. The study-population included 35 LBW and 35 born at term appropriate for gestational age (term AGA) young women. Metabolic evaluations included the composite-insulin sensitivity index (composite ISI). Serum RBP4 was measured with a competitive enzyme-linked immunosorbent assay (ELISA). RBP4 levels were similar in LBW and term AGA women, while composite ISI was significantly lower in the former group. With multivariate logistic regression analysis hormonal contraception (HC) use but not birth weight, diabetes in either parents and body mass index was significantly associated with higher RBP4 levels: odds ratio = 10.6; 95% confidence interval (CI) = 2.4-76.6. In spite of higher RBP4 levels in women under HC, composite ISI was similar in women with or without HC. Women under HC also exhibited significantly higher levels of sex hormone binding globulin (SHBG), triglycerides, cholesterol, and C-reactive protein (CRP), and all of them, but not composite ISI, were significantly correlated with RBP4 levels. In conclusion, RBP4 serum level was not a marker of IR but, for the first time, it is documented a sustained increase of serum RBP4 under HC. Pathophysiological and clinical significance of this novel finding requires further investigations.