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More concern about reproductive effects of phytoestrogens. Environmental estrogens have been under scrutiny in recent years, in both rodent models and humans, particularly with respect to potential effects on reproductive tract development and function after exposure of the fetus via the mother. On p. 798, Jefferson and co-workers focus on genistein, a natural estrogen found in plants and present in soy-based infant formula. Jefferson et al. use a mouse model to extend our understanding of critical windows of exposure to such chemicals by dosing pups directly and only during the first 5 days of life. They show that this is indeed a "critical window" of development; exposure to genistein, at levels comparable to those found in human infants fed soy-based formula, results in a variety of adverse reproductive effects in the female offspring. These include abnormal estrous cyclicity and sub-fertility/infertility that worsen with age. Taken together the spectrum of effects is consistent with the induction of premature reproductive senescence, possibly associated with depletion of oocytes earlier in life and poor oocyte quality. This paper raises concerns owing to its obvious implications regarding use of soy-based formula for human infants.
Isolation and Proteomic Analysis of Mouse Sperm Detergent-Resistant Membrane Fractions. Evidence for Dissociation of Lipid Rafts During Capacitation. Susan B. Sleight, Patricia V. Miranda, Nia- Washington Plaskett, Bernhard Maier, Jeff Lysiak, Heidi Scrable, John C. Herr, and Pablo E.Visconti. Biol Reprod 2005; 73:722–729. Published online 25 May 2005; 10.1095/biolreprod.105.041533
Shedding light into the black box of capacitation. When mammalian sperm are ejaculated, they are motile but unable to fertilize oocytes; they gain this ability while residing in the female reproductive tract during a process termed capacitation. This process involves cholesterol efflux from the sperm plasma membrane, but how this cholesterol efflux leads to a phosphorylation cascade and capacitation is not known. On p. 722, Sleight and colleagues bring modern molecular and biophysical techniques to bear on this problem. Isolation of detergent-resistant membranes (the biochemical equivalent of lipid rafts) during capacitation and subsequent proteomic analysis by tandem mass spectrometry identified lipid raft-associated proteins and the decrease in some of them, such as calveolin I (CAV1), during capacitation. This detailed analysis correlates nicely with evidence published last year in Biology of Reproduction demonstrating reorganization of lipid rafts during capacitation of human (71:1367–1373) and boar (71:253–265) sperm. Overall, the emerging picture is one of cholesterol efflux-induced dissociation of lipid-raft domains in the sperm membrane during capacitation. The next challenge will be to take this proteomic analysis to the stage of identifying the protein dynamics associated with initiating the signaling events leading to capacitation.
Mice Deficient in CHRNA7, a Subunit of the Nicotinic Acetylcholine Receptor, Produce Sperm with Impaired Motility. Christopher Bray, Jung-Ho Son, Priyadarsini Kumar, and Stanley Meizel. Biol Reprod 2005; 73:807–814. Published online 8 June 2005; 10.1095/biolreprod.105.042184
More complexity in sperm motility. Previous studies have indicated that nicotinic acetylcholine receptors are present in sperm and that the alpha 7 subunit of this receptor (CRNA7) is involved in the zona pellucida-triggered acrosome reaction. The plot thickens in a paper on page 807 of this issue, where Bray et al. report that sperm from Crna7 gene knockout (KO) mice have significantly impaired motility and reduced frequency of hyperactivation compared to sperm from wild type (WT) mice. However, no differences were seen in body or testis weight, total sperm number, sperm morphology, and sperm viability. While sperm from KO and WT mice had comparable rates of spontaneous acrosome reactions, another recent publication from this group indicates that the zona pellucida- or acetylcholine-induced acrosome reaction is impaired in sperm lacking CRNA7. Furthermore, earlier studies showed that choline acetyl transferase, which synthesizes acetyl choline, is present in sperm and that inhibitors of this enzyme inhibit sperm motility. The importance of calcium in regulating sperm activities is well known and it was shown previously that acetyl choline can induce calcium uptake. The current study adds to recent gene KO studies showing that several calcium channel proteins, some of which are found only in spermatogenic cells, are essential for normal sperm motility. Additional studies will be needed to determine where CRNA7 sits in the hierarchy of events that regulate calcium-dependent processes in sperm, including changes in motility, capacitation, and the acrosome reaction.
Related articles in Biol Reprod:
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