Study of the acrosome reaction and the fertilizing ability of hamster epididymal cauda spermatozoa treated with antibodies against phospholipase A2 and/or lysophosphatidylcholine
“…Although male infertility because of impaired spermatogenesis has been reported for testis-specific sPLA 2 -IIA Tg mice (75), testis-specific sPLA 2 -V Tg mice are fertile. So far, no reproductive abnormality has been observed in sPLA 2 -V knock-out and Tg mice, even though sPLA 2 -V is expressed in the acrosomes of spermatogenic cells (57) and a potential role of the PLA 2 reaction product, lyso-PC, in the acrosome reaction and fertilization has been proposed (91). By contrast, whether sPLA 2 -V does play a role in defense against bacterial infection and increased atherosclerosis, which are prominent phenotypes of sPLA 2 -IIA Tg mice that may be relevant to the physiological functions of this enzyme (19,20,(22)(23)(24), is difficult to assess with sPLA 2 -V Tg mice because all die in the neonatal period.…”
In an effort to elucidate the functions of secreted phospholipase A 2 (sPLA 2 ) enzymes in vivo, we generated transgenic (Tg) mice for group V sPLA 2 (sPLA 2 -V) and group X sPLA 2 (sPLA 2 -X), which act potently on phosphatidylcholine in vitro. We found that sPLA 2 -V Tg mice died in the neonatal period because of respiratory failure. The lungs of sPLA 2 -V Tg mice exhibited atelectasis with thickened alveolar walls and narrow air spaces, accompanied by infiltration of macrophages and only modest changes in eicosanoid levels. This severe pulmonary defect in sPLA 2 -V Tg mice was attributable to marked reduction of the lung surfactant phospholipids, phosphatidylcholine and phosphatidylglycerol. Given that the expression of sPLA 2 -V is greatly elevated in human lungs with severe inflammation, our present results raise the intriguing possibility that this isozyme may contribute to ongoing surfactant hydrolysis often observed in the lungs of patients with respiratory distress syndrome. In contrast, sPLA 2 -X Tg neonates displayed minimal abnormality of the respiratory tract with normal alveolar architecture and surfactant composition. This unexpected result was likely because sPLA 2 -X protein existed as an inactive zymogen in most tissues. The active form of sPLA 2 -X was detected in tissues with inflammatory granulation in sPLA 2 -X Tg mice. These results suggest that sPLA 2 -X mostly remains inactive under physiological conditions and that its proteolytic activation occurs during inflammation or other as yet unidentified circumstances in vivo.
“…Although male infertility because of impaired spermatogenesis has been reported for testis-specific sPLA 2 -IIA Tg mice (75), testis-specific sPLA 2 -V Tg mice are fertile. So far, no reproductive abnormality has been observed in sPLA 2 -V knock-out and Tg mice, even though sPLA 2 -V is expressed in the acrosomes of spermatogenic cells (57) and a potential role of the PLA 2 reaction product, lyso-PC, in the acrosome reaction and fertilization has been proposed (91). By contrast, whether sPLA 2 -V does play a role in defense against bacterial infection and increased atherosclerosis, which are prominent phenotypes of sPLA 2 -IIA Tg mice that may be relevant to the physiological functions of this enzyme (19,20,(22)(23)(24), is difficult to assess with sPLA 2 -V Tg mice because all die in the neonatal period.…”
In an effort to elucidate the functions of secreted phospholipase A 2 (sPLA 2 ) enzymes in vivo, we generated transgenic (Tg) mice for group V sPLA 2 (sPLA 2 -V) and group X sPLA 2 (sPLA 2 -X), which act potently on phosphatidylcholine in vitro. We found that sPLA 2 -V Tg mice died in the neonatal period because of respiratory failure. The lungs of sPLA 2 -V Tg mice exhibited atelectasis with thickened alveolar walls and narrow air spaces, accompanied by infiltration of macrophages and only modest changes in eicosanoid levels. This severe pulmonary defect in sPLA 2 -V Tg mice was attributable to marked reduction of the lung surfactant phospholipids, phosphatidylcholine and phosphatidylglycerol. Given that the expression of sPLA 2 -V is greatly elevated in human lungs with severe inflammation, our present results raise the intriguing possibility that this isozyme may contribute to ongoing surfactant hydrolysis often observed in the lungs of patients with respiratory distress syndrome. In contrast, sPLA 2 -X Tg neonates displayed minimal abnormality of the respiratory tract with normal alveolar architecture and surfactant composition. This unexpected result was likely because sPLA 2 -X protein existed as an inactive zymogen in most tissues. The active form of sPLA 2 -X was detected in tissues with inflammatory granulation in sPLA 2 -X Tg mice. These results suggest that sPLA 2 -X mostly remains inactive under physiological conditions and that its proteolytic activation occurs during inflammation or other as yet unidentified circumstances in vivo.
Spermatozoa are constantly exposed to the interphase between oxidation through high amounts of reactive oxygen species (ROS) and leukocytes, and reduction by means of scavengers and antioxidants. Considering the very special functions as being the only cells with such high polarization and exerting their functions outside the body, even in a different individual, the female genital tract, the membranes of these cells are chemically composed of an extraordinary high amount of polyunsaturated fatty acids. This in turn, renders them very susceptible to oxidative stress, which is defined as an imbalance between oxidation and reduction towards the oxidative status. As a result, ROS deriving from both leukocytes and the male germ cells themselves cause a process called 'lipid peroxidation' and other damages to the sperm cell. On the other hand, a certain limited amount of ROS is essential in order to trigger vital physiological reactions in cells, including capacitation or the acrosome reaction in sperm. The treatment of patients with antioxidants to compensate the oxidative status caused by oxidative stress is highly debated as uncontrolled antioxidative treatment might derail the system towards the reduced status, which is also unphysiological and can even induce cancer. This paradox is called the 'antioxidant paradox'. Therefore, a proper andrological diagnostic work-up, including the evaluation of ROS levels and the antioxidant capacity of the semen, has to be carried out beforehand, aimed at keeping the fine balance between oxidation and scavenging of vital amounts of ROS.
“…83,84) The acrosome reaction of hamster spermatozoa and subsequent fertilization in vitro is suppressed by anti-sPLA 2 antibody, and this effect was reversed by LPC, a major PLA 2 reaction product. 85) Accumulation of LPC occurs following in vitro incubation of spermatozoa, and LPC stimulates the fertilizing ability of spermatozoa and induces the changes in the zona pellucida and the oolemma which allow sperm-egg fusion. [86][87][88] Our recent immunohistochemical study has revealed that sPLA 2 -IID, -IIE, -IIF, -V, and -X are expressed in spermatogenic cells (Murakami M., unpublished data).…”
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