Loss of the Na(+)/H(+) exchanger NHE8 causes male infertility in mice by disrupting acrosome formation

Mammalian sperm feature a specialized secretory organelle on the anterior part of the sperm nucleus, the acrosome, which is essential for male fertility. It is formed by a fusion of Golgi-derived vesicles. We show here that the predominantly Golgi-resident Na+/H+ exchanger NHE8 localizes to the developing acrosome of spermatids. Similar to wild-type mice, Nhe8-/- mice generated Golgi-derived vesicles positive for acrosomal markers and attached to nuclei, but these vesicles failed to form large acrosomal granules and the acrosomal cap. Spermatozoa from Nhe8-/- mice completely lacked acrosomes, were round-headed, exhibited abnormal mitochondrial distribution and displayed decreased motility, resulting in selective male infertility. Of note, similar features are also found in globozoospermia, one of the causes of male infertility in humans. Germ cell-specific, but not Sertoli cell-specific Nhe8 disruption recapitulated the globozoospermia phenotype, demonstrating that NHE8's role in spermiogenesis is germ cell-intrinsic. Our work has uncovered a crucial role of NHE8 in acrosome biogenesis and suggests that some forms of human globozoospermia might be caused by a loss of function of this Na+/H+ exchanger. It points to NHE8 as a candidate gene for human globozoospermia and a possible drug target for male contraception

Downward shift of infrared conductivity spectral weight at the DDW transition: role of anisotropy

We consider the motion of conductivity spectral weight at a finite-temperature phase transition at which $d_{x^2-y^2}$ density-wave (DDW) order develops. We show that there is a shift of spectral weight to higher frequencies if the quasiparticle lifetime is assumed to be isotropic, but a shift to lower frequencies if the quasiparticle lifetime is assumed to be anisotropic. We suggest that this is consistent with recent experiments on the pseudogap phase of the cuprate superconductors and, therefore, conclude that the observation of a downward shift in the spectral weight at the pseudogap temperature does not militate against the DDW theory of the pseudogap.Comment: 8 pages, 7 figures. Added reference

LRRC8/VRAC anion channels are required for late stages of spermatid development in mice

Spermatogenesis is a highly complex developmental process that occurs primarily in seminiferous tubules of the testes and requires additional maturation steps in the epididymis and beyond. Mutations in many different genes can lead to defective spermatozoa and hence to male infertility. Some of these genes encode for ion channels and transporters that play roles in various processes such as cellular ion homeostasis, signal transduction, sperm motility, and the acrosome reaction. Here we show that germ cell-specific, but not Sertoli cell-specific, disruption of Lrrc8a leads to abnormal sperm and male infertility in mice. LRRC8A (leucine-rich repeat containing 8 A) is the only obligatory subunit of heteromeric volume-regulated VRAC anion channels. Its ablation severely compromises cell volume regulation by completely abolishing the transport of anions and osmolytes through VRAC. Consistent with impaired volume regulation, the cytoplasm of late spermatids appeared swollen. These cells failed to properly reduce their cytoplasm during further development into spermatozoa and later displayed severely disorganized mitochondrial sheaths in the midpiece region as well as angulated or coiled flagella. These changes, which progressed in severity on the way to the epididymis, resulted in dramatically reduced sperm motility. Our work shows that VRAC, probably through its role in cell volume regulation, is required in a cell-autonomous manner for proper sperm development and explains the male infertility of Lrrc8a(-/-) mice and the spontaneous mouse mutant ébouriffé

Marginal Fermi liquid analysis of 300 K reflectance of Bi2Sr2CaCu2O8+x

We use 300 K reflectance data to investigate the normal-state electrodynamics of the high temperature superconductor Bi$_{2}$Sr$_{2}$CaCu$_{2}$O$_{8+\delta}$ over a wide range of doping levels. The data show that at this temperature the free carriers are coupled to a continuous spectrum of fluctuations. Assuming the Marginal Fermi Liquid (MFL) form as a first approximation for the fluctuation spectrum, the doping-dependent coupling constant $\lambda (p)$ can be estimated directly from the slope of the reflectance spectrum. We find that $\lambda (p)$ decreases smoothly with the hole doping level, from underdoped samples with $p=0.103$ ($T_c = 67$ K) where $\lambda (p)= 0.93$ to overdoped samples with $p=0.226$, ($T_c= 60$ K) where $\lambda(p)= 0.53$. An analysis of the intercept and curvature of the reflectance spectrum shows deviations from the MFL spectrum symmetrically placed at the optimal doping point $p=0.16$. The Kubo formula for the conductivity gives a better fit to the experiments with the MFL spectrum up to 2000 cm$^{-1}$ and with an additional Drude component or an additional Lorentz component up to 7000 cm$^{-1}$. By comparing three different model fits we conclude that the MFL channel is necessary for a good fit to the reflectance data. Finally, we note that the monotonic variation of the reflectance slope with doping provides us with an independent measure of the doping level for the Bi-2212 system.Comment: 11 pages, 11 figure

Optical Response for the d-density wave model

We have calculated the optical conductivity and the Raman response for the d-density wave model, proposed as a possible explanation for the pseudogap seen in high Tc cuprates. The total optical spectral weight remains approximately constant on opening of the pseudogap for fixed temperature. This occurs because there is a transfer of weight from the Drude peak to interband transitions across the pseudogap. The interband peak in the optical conductivity is prominent but becomes progressively reduced with increasing temperature, with impurity scattering, which distributes it over a larger energy range, and with ineleastic scattering which can also shift its position, making it difficult to have a direct determination of the value of the pseudogap. Corresponding structure is seen in the optical scattering rate, but not necessarily at the same energies as in the conductivity.Comment: 14 pages, 15 figures, final revised version published in PR

Magnetic resonance at 41 meV and charge dynamics in YBa_2Cu_3O_6.95

We report an Eliashberg analysis of the electron dynamics in YBa_2Cu_3O_6.95. The magnetic resonance at 41 meV couples to charge carriers and defines the characteristic shape in energy of the scattering rate \tau^{-1}(T,\omega) which allows us to construct the charge-spin spectral density I^2\chi(\omega,T) at temperature T. The T dependence of the weight under the resonance peak in I^2\chi(\omega,T) agrees with experiment as does that of the London penetration depth and of the microwave conductivity. Als, at T=0 condensation energy, the fractional oscillator strength in the condensate, and the ratio of gap to critical temperature agree well with the data.Comment: 7 Pages, 3 Figures, accepted for publication in Europhysics Letter

Sum rules and electrodynamics of high-Tc cuprates in the pseudogap state

We explore connections between the electronic density of states (DOS) in a conducting system and the frequency dependence of the scattering rate $1/\tau(\omega)$ inferred from infrared spectroscopy. We show that changes in the DOS upon the development of energy gaps can be reliably tracked through the examination of the $1/\tau(\omega)$ spectra using the sum rules discussed in the text. Applying this analysis to the charge dynamics in high-$T_c$ cuprates we found radically different trends in the evolution of the DOS in the pseudogap state and in the superconducting state.Comment: 4 pages, 3 figure

Evolution of Magnetic and Superconducting Fluctuations with Doping of High-Tc Superconductors (An electronic Raman scattering study)

For YBa_2Cu_3O_{6+\delta} and Bi_2Sr_2CaCu_2O_8 superconductors, electronic Raman scattering from high- and low-energy excitations has been studied in relation to the hole doping level, temperature, and energy of the incident photons. For underdoped superconductors, it is concluded that short range antiferromagnetic (AF) correlations persist with hole doping and doped single holes are incoherent in the AF environment. Above the superconducting (SC) transition temperature T_c the system exhibits a sharp Raman resonance of B_1g symmetry and about 75 meV energy and a pseudogap for electron-hole excitations below 75 meV, a manifestation of a partially coherent state forming from doped incoherent quasi-particles. The occupancy of the coherent state increases with cooling until phase ordering at T_c produces a global SC state.Comment: 5 pages, 4 EPS figures; SNS'97 Proceedings to appear in J. Phys. Chem. Solid