Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

The importance of improving diet in 'Securing Scotland's Health': exploring differences in dietary intake between Scotland and England

Background: Various factors have been investigated to account for the higher premature death rates in Scotland compared to England. Higher levels of deprivation in Scotland provide a partial explanation for these differences but recent work comparing areas of the UK with similar deprivation profiles and low life expectancy has shown that this is not the only reason. One hypothesis yet to be tested adequately is differences in diet and nutrition. Objective: To conduct a comparative analysis of dietary intake between Scotland and England using pooled food purchase data from the Living Costs and Food Survey (LCFS) from 2001 to 2012 and to assess differences in equivalised income quintiles (controlling for survey year, age of household reference person, and age household reference person left full-time education). Results: Lower intakes of fruit and vegetables, oil rich fish, fibre, vitamin A, folate, vitamin C and vitamin D and higher intakes of red and processed meat, whole milk, butter, savoury snacks, confectionary, soft drinks, saturated fat and NMES (added sugar and sugar in fruit juice), sodium and alcohol were found for Scotland compared to England. Differences between Scotland and England were higher for those on lower incomes for dietary components known to be related to health outcomes. For example fruit consumption was 14g/day lower for the lowest income quintile compared to 4 g/day lower in the highest quintile for Scotland versus England. Conclusions: A poorer diet in Scotland compared to England, particularly among disadvantaged groups, is likely to be one of the reasons for excess mortality. The current evidence on the continued poor diet in Scotland, particularly in disadvantaged groups, should not be ignored. Identifying effective, culturally appropriate approaches to improve diet across the population and notably in the most deprived areas needs further investment. Funded by NHS Health Scotland. Data provided by DEFRA, ONS and the UK Data Archive.