RESUMEN
Sperm DNA damage is considered a predictive factor for the clinical outcomes of patients undergoing ART. Laboratory evidence suggests that zygotes and developing embryos have adopted specific response and repair mechanisms to repair DNA damage of paternal origin. We have conducted a systematic review in accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify and review the maternal mechanisms used to respond and repair sperm DNA damage during early embryonic development, how these mechanisms operate and their potential clinical implications. The literature search was conducted in Ovid MEDLINE and Embase databases until May 2021. Out of 6297 articles initially identified, 36 studies were found to be relevant through cross referencing and were fully extracted. The collective evidence in human and animal models indicate that the early embryo has the capacity to repair DNA damage within sperm by activating maternally driven mechanisms throughout embryonic development. However, this capacity is limited and likely declines with age. The link between age and decreased DNA repair capacity could explain decreased oocyte quality in older women, poor reproductive outcomes in idiopathic cases and patients who present high sperm DNA damage. Ultimately, further understanding mechanisms underlying the maternal repair of sperm DNA damage could lead to the development of targeted therapies to decrease sperm DNA damage, improved oocyte quality to combat incoming DNA insults or lead to development of methodologies to identify individual spermatozoa without DNA damage.
Asunto(s)
Daño del ADN , Reparación del ADN , Anciano , Animales , Daño del ADN/genética , Reparación del ADN/genética , Desarrollo Embrionario/genética , Femenino , Humanos , Masculino , Oocitos/fisiología , Embarazo , Espermatozoides/fisiologíaRESUMEN
Phase correction of FT-ICR data yields an absorption spectrum that offers a gain by up to a factor of 2 in mass resolving power (at half-maximum peak height), compared to conventional magnitude-mode display. That improvement is equivalent to doubling the applied magnetic field strength, without loss in signal-to-noise (S/N) ratio, provided that the time-domain data are padded with an equal number of zeroes before FFT. Our simple, visual, user-interactive algorithm quickly corrects for zero-order and first-order variation of phase with frequency. We find that the theoretical mass resolving power enhancement for pressure-limited absorption-mode over magnitude-mode line shape depends on the collision mechanism: factor of 1.40 for hard sphere vs 3(1/2) for Langevin (ion: induced dipole). Thus, the experimental enhancement in mass resolving power (factor of 1.43 +/- 0.09) for isotopically resolved peaks in the FT-ICR mass spectra of electrosprayed bovine carbonic anhydrase (approximately 29 kDa) directly supports the hard-sphere collision model. Optimal implementation of phasing requires the following: (a) a delay between excitation and detection of less than half of one sampling interval to avoid baseline "roll" and Gibb's oscillations; (b) accurate analog-to-digital conversion; (c) a sufficiently long acquisition period to yield several data points per absorption-mode peak width at half-maximum peak height; and (d) avoidance of FT-ICR apodization functions (e.g., Hamming and Hanning) that suppress the initial time-domain data. Pulsed single-frequency excitation (duration much less than the reciprocal of the Nyquist bandwidth) can eliminate higher than first-order variation of phase with frequency. Phased FT-ICR spectra should prove especially desirable for analysis of complex mixtures, for resolving isotopic distributions in electrosprayed multiply charged macromolecules and for characterizing ion collisions (and thus ion size and shape).
Asunto(s)
Análisis de Fourier , Espectrometría de Masas/métodos , Modelos Teóricos , Animales , Anhidrasas Carbónicas/química , Bovinos , Procesamiento de Imagen Asistido por Computador , Mioglobina/químicaRESUMEN
We present the design and preliminary results from a Fourier transform ion cyclotron resonance (ICR) mass spectrometer developed for the direct detection of UV/visible laser-induced fluorescence of trapped, mass-selected, gas-phase ions. A 3 T superconducting magnet and an open-ended multi-section cylindrical Penning trap capture and confine ions created by electron impact or laser desorption. Azimuthal quadrupolar excitation in the presence of ion/neutral collisions cools, axializes and mass selects ions as they fill the trap. A pulsed dye laser pumped by an Nd:YAG laser provides electronic energy excitation. A Brewster window and baffles on each side of the vacuum chamber reduce the scattered light from the excitation laser. Laser-induced fluorescence is collected from mirrors and lenses and directed through a quartz window and fiber-optic bundle to a photomultiplier. The ICR and optical events are controlled by a modular ICR data station and GPIB and RS-232 interfaces. An excitation spectrum is demonstrated for atomic Ba+ ions, and should extend to laser-induced fluorescence of virtually any stable positive or negative gas-phase ions of arbitrary molecular weight: molecular or quasimolecular ions, fragment ions, adduct ions, and ions formed from ion/molecule reactions.