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Papers by William Holt
Fertility and Sterility, 2009
Objective: To analyze any possible dynamic correlation between sperm DNA fragmentation and sperm ... more Objective: To analyze any possible dynamic correlation between sperm DNA fragmentation and sperm viability. Design: The rate of viability loss and the rate of increase of the frequency of sperm cells with fragmented DNA were determined at 0, 1.5, 4.5, and 24.0 hours after thawing samples from donors with proven fertility. Setting: Academic biology and reproductive medicine centers. Patient(s): Fifteen male donors with proven fertility for a maximum of six births at the reproductive medicine center. Intervention(s): None. Main Outcome Measure(s): Sperm DNA fragmentation and viability dynamics expressed as logarithmic coefficients of change.
Journal of reproduction and fertility. Supplement
The functions necessary for normal fertilization to occur in vivo or in vitro are examined and a ... more The functions necessary for normal fertilization to occur in vivo or in vitro are examined and a rational approach to identifying the main features of a fertilizing spermatozoon are developed. It is concluded that methods for testing the quality of spermatozoa must probe the dynamic changes experienced by the spermatozoa during capacitation or under stressful incubation conditions. Recent developments in the multivariate analysis of sperm motility data are used to illustrate the success that can be achieved by this approach. Ideally, changes in sperm motility characteristics should be correlated with an assessment of capacitation status. However, until the capacitation status of any individual cell can be clearly defined this will remain problematic.
ABSTRACT In vitro production (IVP) of porcine embryos is currently suboptimal compared with IVP i... more ABSTRACT In vitro production (IVP) of porcine embryos is currently suboptimal compared with IVP in species such as mice and cattle. In vitro fertilization (IVF) usually involves the co-culture of oocytes and spermatozoa in a medium droplet. Oocyte quality is the focus of many studies. In vivo, the quality of spermatozoa is as important as the oocyte, and females have many mechanisms to select the highest quality spermatozoa for their oocytes. Oviductal proteins have been shown to affect sperm motility of subpopulations within an ejaculate. The present study was carried out to investigate normal and polyspermic fertilization rates of spermatozoa exposed to oviductal epithelial apical plasma membrane (APM) proteins, a mixture of peripheral proteins extracted by 1 M NaCl from isolated oviductal apical plasma membranes, prior to co-culture with oocytes in IVF. Porcine oocytes were aspirated from ovaries and grade I quality oocytes (cumulus–oocyte complexes with a spherical shape, visible nucleus, even-density cytoplasm, and multiple layers of cumulus cells) were selected and matured for 48 h in TCM-199 supplemented with LH (0.5 µg mL-1), FSH (0.5 µg mL-1), and EGF (10 ng mL-1). Ejaculates were washed through a Percoll gradient to obtain a concentrated pellet. Spermatozoa were diluted in capacitation–fertilization medium in the presence or absence of APM proteins (100 µg mL-1), incubated for 10 min, and then co-cultured with oocytes for 6 h in modified Tween medium B with milk powder medium (Abeydeera and Day 1997 Theriogenology 48, 537–544) supplemented with BSA (0.4%) and sodium bicarbonate (5 mM). Presumptive zygotes were cultured in NCSU23 medium for a further 48 h. The oocytes/zygotes were then fixed and stained with propidium iodide for evaluation by confocal microscopy for fertilization and cleavage (n = 1235 oocytes). Fertilization rates were compared between treatments in a chi-squared test using the Mantel-Haenszel approach. The overall fertilization rate was significantly higher (78 vs. 86%) when spermatozoa were incubated in the presence of APM proteins (P < 0.05), and in the group of fertilized oocytes, polyspermic fertilization (47 vs. 21%) was significantly reduced when spermatozoa were exposed to APM proteins (P < 0.01). However, cleavage rates were not different. These results suggest that exposure of spermatozoa to APM proteins prior to IVF increases the fertilization rate and decreases the incidence of polyspermic penetration.
Reproduction in Domestic Animals
Description based upon print version of record.
Reproduction Fertility and Development
We have developed and validated a computer-assisted sperm-motility assessment (CASA) method for u... more We have developed and validated a computer-assisted sperm-motility assessment (CASA) method for use with the emerging amphibian model Silurana tropicalis. The testicular sperm-activation method was validated by analysing activation replicate coefficients of variation, effects of tracking time settings on velocity distributions and the relative partitioning of differentially motile sperm subpopulations between matched right and left testes. Two major sperm subpopulations were identified using multivariate pattern analysis and their relative frequencies were consistent between samples from matched right and left testes and from randomly drawn subsets of six frogs sampled from the total set of 16 frogs. The power of this approach for detecting treatment effects targeting the hypothalamic–pituitary–gonadal axis was investigated by injecting a group of frogs with 100 IU human chorionic gonadotrophin (hCG) 2 h before sampling and comparing their sperm-subpopulation frequencies with non-i...
Molecular human reproduction, Jan 9, 2015
Most male mammals produce far more spermatozoa on a daily basis than is strictly necessary for re... more Most male mammals produce far more spermatozoa on a daily basis than is strictly necessary for reproduction and females have evolved mechanisms that prevent all but a small minority from reaching the vicinity of their oocytes. One potential explanation for the stringent selection is that females have developed these mechanisms as a way of avoiding polyspermy as well as exercising post-copulatory choice over the characteristics of the fertilizing spermatozoon. Relatively little is known about how these processes would operate, but here we use evidence from biochemical, molecular and genetic studies of sperm transport in support of a hypothesis proposing that the female reproductive tract can read and interpret a spermatozoon's 'molecular passport' or genetic signature. Such a signature would permit only a highly selected sperm population to reach and fertilize the oocyte. Moreover, the selection criteria might not only be concerned with successful fertilizing ability, but...
Fertility and Sterility, 2009
Objective: To analyze any possible dynamic correlation between sperm DNA fragmentation and sperm ... more Objective: To analyze any possible dynamic correlation between sperm DNA fragmentation and sperm viability. Design: The rate of viability loss and the rate of increase of the frequency of sperm cells with fragmented DNA were determined at 0, 1.5, 4.5, and 24.0 hours after thawing samples from donors with proven fertility. Setting: Academic biology and reproductive medicine centers. Patient(s): Fifteen male donors with proven fertility for a maximum of six births at the reproductive medicine center. Intervention(s): None. Main Outcome Measure(s): Sperm DNA fragmentation and viability dynamics expressed as logarithmic coefficients of change.
Journal of reproduction and fertility. Supplement
The functions necessary for normal fertilization to occur in vivo or in vitro are examined and a ... more The functions necessary for normal fertilization to occur in vivo or in vitro are examined and a rational approach to identifying the main features of a fertilizing spermatozoon are developed. It is concluded that methods for testing the quality of spermatozoa must probe the dynamic changes experienced by the spermatozoa during capacitation or under stressful incubation conditions. Recent developments in the multivariate analysis of sperm motility data are used to illustrate the success that can be achieved by this approach. Ideally, changes in sperm motility characteristics should be correlated with an assessment of capacitation status. However, until the capacitation status of any individual cell can be clearly defined this will remain problematic.
ABSTRACT In vitro production (IVP) of porcine embryos is currently suboptimal compared with IVP i... more ABSTRACT In vitro production (IVP) of porcine embryos is currently suboptimal compared with IVP in species such as mice and cattle. In vitro fertilization (IVF) usually involves the co-culture of oocytes and spermatozoa in a medium droplet. Oocyte quality is the focus of many studies. In vivo, the quality of spermatozoa is as important as the oocyte, and females have many mechanisms to select the highest quality spermatozoa for their oocytes. Oviductal proteins have been shown to affect sperm motility of subpopulations within an ejaculate. The present study was carried out to investigate normal and polyspermic fertilization rates of spermatozoa exposed to oviductal epithelial apical plasma membrane (APM) proteins, a mixture of peripheral proteins extracted by 1 M NaCl from isolated oviductal apical plasma membranes, prior to co-culture with oocytes in IVF. Porcine oocytes were aspirated from ovaries and grade I quality oocytes (cumulus–oocyte complexes with a spherical shape, visible nucleus, even-density cytoplasm, and multiple layers of cumulus cells) were selected and matured for 48 h in TCM-199 supplemented with LH (0.5 µg mL-1), FSH (0.5 µg mL-1), and EGF (10 ng mL-1). Ejaculates were washed through a Percoll gradient to obtain a concentrated pellet. Spermatozoa were diluted in capacitation–fertilization medium in the presence or absence of APM proteins (100 µg mL-1), incubated for 10 min, and then co-cultured with oocytes for 6 h in modified Tween medium B with milk powder medium (Abeydeera and Day 1997 Theriogenology 48, 537–544) supplemented with BSA (0.4%) and sodium bicarbonate (5 mM). Presumptive zygotes were cultured in NCSU23 medium for a further 48 h. The oocytes/zygotes were then fixed and stained with propidium iodide for evaluation by confocal microscopy for fertilization and cleavage (n = 1235 oocytes). Fertilization rates were compared between treatments in a chi-squared test using the Mantel-Haenszel approach. The overall fertilization rate was significantly higher (78 vs. 86%) when spermatozoa were incubated in the presence of APM proteins (P < 0.05), and in the group of fertilized oocytes, polyspermic fertilization (47 vs. 21%) was significantly reduced when spermatozoa were exposed to APM proteins (P < 0.01). However, cleavage rates were not different. These results suggest that exposure of spermatozoa to APM proteins prior to IVF increases the fertilization rate and decreases the incidence of polyspermic penetration.
Reproduction in Domestic Animals
Description based upon print version of record.
Reproduction Fertility and Development
We have developed and validated a computer-assisted sperm-motility assessment (CASA) method for u... more We have developed and validated a computer-assisted sperm-motility assessment (CASA) method for use with the emerging amphibian model Silurana tropicalis. The testicular sperm-activation method was validated by analysing activation replicate coefficients of variation, effects of tracking time settings on velocity distributions and the relative partitioning of differentially motile sperm subpopulations between matched right and left testes. Two major sperm subpopulations were identified using multivariate pattern analysis and their relative frequencies were consistent between samples from matched right and left testes and from randomly drawn subsets of six frogs sampled from the total set of 16 frogs. The power of this approach for detecting treatment effects targeting the hypothalamic–pituitary–gonadal axis was investigated by injecting a group of frogs with 100 IU human chorionic gonadotrophin (hCG) 2 h before sampling and comparing their sperm-subpopulation frequencies with non-i...
Molecular human reproduction, Jan 9, 2015
Most male mammals produce far more spermatozoa on a daily basis than is strictly necessary for re... more Most male mammals produce far more spermatozoa on a daily basis than is strictly necessary for reproduction and females have evolved mechanisms that prevent all but a small minority from reaching the vicinity of their oocytes. One potential explanation for the stringent selection is that females have developed these mechanisms as a way of avoiding polyspermy as well as exercising post-copulatory choice over the characteristics of the fertilizing spermatozoon. Relatively little is known about how these processes would operate, but here we use evidence from biochemical, molecular and genetic studies of sperm transport in support of a hypothesis proposing that the female reproductive tract can read and interpret a spermatozoon's 'molecular passport' or genetic signature. Such a signature would permit only a highly selected sperm population to reach and fertilize the oocyte. Moreover, the selection criteria might not only be concerned with successful fertilizing ability, but...