ACTA ENDOCRINOLOGICA (BUC)

Objective: The goal of this research is to investigate whether melatonin, a circadian informant, is implicated in idiopathic oligospermia in men.\r\nSubjects and methods: 12 men (mean age 30.5 yr) with normal sexual function diagnosed with idiopathic oligospermia and 8 healthy men were included. In urine 6-sulfatoxymelatonin (aMT6s), a reliable index of melatonin secretion and gonadotropins, LH and FSH were assayed. In plasma LH, FSH, DHEA-S, 17-OH progesterone, testosterone, free testosterone, SHBG were measured at 08:00.\r\nResults: As expected, in the infertile group reproductive hormones were within normal limits but persisted low testosterone and high gonadotropins. Estimated bioavailable testosterone also showed a significant decrease (p=0.03). Evaluation of individual differences in circadian production of both melatonin and gonadotropins exhibited substantial changes in their secretion pattern from the phase shifts to loss of rhythm for aMT6s. The reduced amplitudes (p=0.04) of aMT6s were associated with a longer duration of melatonin secretion (p< 0.001) as estimated from onset/offset time and a reduced ratio between night- and daytime; the mean 24h amount of aMT6s tended to decrease at significant limit (p=0.05); no significant correlation between aMT6s and gonadotropins was observed compared with the control group. The amplitudes of gonadotropins were lower while their mean 24 h amount showed a moderate increase.\r\nConclusions: The present findings suggest that the significant increase in the duration of melatonin secretion may contribute to the imbalance of reproductive hormones that affect spermatogenesis; aMT6s, urinary metabolite of melatonin may be a sensitive predictor in circadian disorders of reproductive axis.

Objective. Estrogen receptor alpha (ESR1) polymorphisms (XbaI and PvuII) and vitamin D receptor (VDR) polymorphisms (FokI, BsmI, ApaI and TaqI) are the most frequently studied regarding the correlations with the infertility in males, but the results are controversial. The purpose of this study is to evaluate possible correlations between hormonal markers, VDR and ESR1 genotypes and semen analysis, in order to bring new data for a better understanding of male infertility. Subjects and Methods. 42 infertile men and 28 controls were enrolled. The polymorphisms of VDR gene (ApaI, TaqI, BsmI and FokI) and ESR1 (XbaI and PvuII) were performed by PCR-RFLP, along with hormonal markers. Results. An important correlation between PvuII polymorphism and infertility status was revealed. A significant difference between control and infertility group regarding the presence of BsmI (A>G) and ApaI (G>T) polymorphisms was observed in infertile group, prolactin and DHEA were found to correlate significantly statistic with BsmI GG genotype, whereas ApaI AA genotype correlates with prolactin and SHBG levels. Conclusions. By a multivariate analysis, we demonstrated a cumulative effect of some genetic variants in the hormonal status of infertile patients. Therefore, we show that specific genetic variants of ESR1 and VDR genes may jointly influence human spermatogenesis.

Aim. To investigate the cause of infertility in an azoospermic man and to describe the phenotype of a new 46,XX male case. Case report. We present the case of an infertile man, 33 years old, with a history of several years of infertility, diagnosed with the 46,XX male syndrome, SRY positive. The patient was diagnosed by clinical, hormonal, ultrasound and genetic criteria. Our patient was born at 39 weeks of pregnancy, from unrelated parents. The mother’s age was 22 years old and father’s age was 23 years old at the time of the conception. Both of his parents were exposed to chemical noxae before his conception. The case we report is a SRY positive 46,XX male with complete masculinization, confirmed by FISH and molecular analyses, caused by an X/Y chromosome inter-change during paternal meiosis. Conclusions. In our case, the SRY translocation, could probably be related to the paternal exposure to external factors like chemical noxae, but more data are necessary. Cytogenetic and molecular analyses are necessary for an accurate diagnosis, as well as endocrine testing and pelvis ultrasound.

Introduction. Vitamin D (VD) levels were correlated with different health conditions, including reproductive disorders in males. Vitamin D action is mediated through vitamin D receptor (VDR), which acts as a transcription factor. VDR gene promoter is embedded in a GC-rich island. The VDR gene has been shown to have several polymorphisms that affect the receptor function. Aim. To examine the relationship between Cdx- 2 polymorphism (rs17883968), the methylation status of VDR’s promoter and serum levels of 25-hydroxyvitamin D in male infertility. Patients and Methods. A total of 69 infertile men and 37 age-matched controls were enrolled in this study. Vitamin D level assessments were detected using the electrochemiluminescent method. Cdx-2 VDR polymorphism identification was performed by PCR on DNA samples from blood, followed by restriction. Methylation of VDR gene promoter was assessed by qMS-PCR using bisulfite-treated DNA from fresh sperm. Results. Vitamin D levels was found to be significantly decreased in infertile groups compared the controls (p=0.0279). The GG genotype was found in a higher percentage in controls and the AA genotype was higher in infertile group (p=0.0056). Infertile homozygote (GG) and heterozygote (GA) individuals had significantly higher vitamin D levels than AA homozygote. Methylation is higher in individuals with lower vitamin D levels and AA genotype is characterized by higher methylation values. Conclusion. The results provide new insights of Cdx-2 polymorphism is involved in vitamin D deficiency, highlighting the important role of epigenetic modification of vitamin D receptor and male infertility along with the genetic context.