The role of SPRASA in female fertility

Fertility is a complex process and infertility can have many causes. Sperm protein reactive with antisperm antibody (SPRASA)/sperm lysozyme-like protein 1 is a protein discovered as the target of autoantibodies in infertile men and previously thought to be expressed only in sperm. Using a bovine in vitro fertilization model, we have shown that SPRASA antiserum reduced sperm binding to zona-free oocytes and the development of embryos to morulae but did not affect the postfertilization cleavage rate to 2 cells or sperm motility. We demonstrated that SPRASA was expressed in ovarian follicles, corpora lutea, and oocytes by a combination of reverse transcription-polymerase chain reaction and immunohistochemistry. Female mice immunized with SPRASA had profound infertility following timed matings and those mice that did become pregnant had reduced fetal viability. The levels of antibodies reactive with SPRASA in 204 fertile and 202 infertile couples were elevated in 3 infertile but no fertile women. Together, these results indicate that SPRASA has a role in female fertility.</p

The Reduction in Circulating Melatonin Level May Contribute to the Pathogenesis of Ovarian Cancer: A Retrospective Study

Abstract Ovarian cancer is the third most common gynaecological malignancy. Changes in circadian rhythms such as bright light exposure may affect female reproductive physiology. Night shift work is associated with higher risks of developing gynaecological cancers. In addition, the season of birth is also suggested as an important environmental risk factor for developing gynaecological cancers. Melatonin may play an important role in this association as a marker of circadian rhythms. Serum from 96 women with ovarian cancer and 40 healthy women were collected and the level of melatonin was measured. In addition 277 women with ovarian cancer and 1076 controls were retrospectively collected for season of birth analysis over seven years. The serum levels of melatonin were significantly lower in women with ovarian cancer compared with healthy women (p&lt;0.05). However there was no difference in melatonin levels in perimenopausal and postmenopausal patients. In addition, there is no statistically significant difference in seasonal distribution of birth between ovarian cancer patients and the control group. The melatonin levels in ovarian cancer patients and controls were not associated with the season of birth. Our results demonstrate the lower serum levels of melatonin in ovarian cancer patients which may contribute to the pathogenesis of ovarian cancer. The incidence of ovarian cancer was not associated with the season of birth. The serum levels of melatonin do not appear to be associated with season of birth in ovarian cancer patients

Antiphospholipid antibodies increase the levels of mitochondrial DNA in placental extracellular vesicles: Alarmin-g for preeclampsia

The pathogenesis of preeclampsia remains unclear but placental factors are known to play a crucial role causing maternal endothelial cell dysfunction. One potential factor is placental micro-and nano-vesicles. Antiphospholipid antibodies (aPL) increase the risk of preeclampsia ten-fold, in part by damaging the mitochondria in the syncytiotrophoblast. Since mitochondrial DNA (mtDNA) is a danger-associated molecular pattern (DAMP/alarmin) that may activate endothelial cells, the aims of the current study were to investigate whether aPL affect the number of placental vesicles extruded, their mtDNA content and their ability to activate endothelial cells. Exposure of first trimester human placental explants to aPL affected neither the number nor size of extruded micro-and nano-vesicles (n = 5), however their levels of mtDNA were increased (n = 6). These vesicles significantly activated endothelial cells (n = 5), which was prevented by blocking toll-like receptor 9 (TLR-9), a receptor for extracellular DNA. Thus, aPL may increase the risk of preeclampsia in part by increasing the amount of mtDNA associated with placental vesicles. That mitochondrial DNA is recognised as a DAMP by TLR-9 to cause endothelial cell activation, raises the possibility that placental vesicles or TLR-9 might be a target for pharmaceutical intervention to reduce the consequences of aPL in pregnancy.Funding Agencies|University of Auckland Health Research Doctoral Scholarship; Freemasons Postgraduate Scholarship; Health Research Council of New Zealand [15/209]</p

The Role of SPRASA in Female Fertility

Fertility is a complex process and infertility can have many causes. Sperm protein reactive with antisperm antibody (SPRASA)/sperm lysozyme-like protein 1 is a protein discovered as the target of autoantibodies in infertile men and previously thought to be expressed only in sperm. Using a bovine in vitro fertilization model, we have shown that SPRASA antiserum reduced sperm binding to zona-free oocytes and the development of embryos to morulae but did not affect the postfertilization cleavage rate to 2 cells or sperm motility. We demonstrated that SPRASA was expressed in ovarian follicles, corpora lutea, and oocytes by a combination of reverse transcription-polymerase chain reaction and immunohistochemistry. Female mice immunized with SPRASA had profound infertility following timed matings and those mice that did become pregnant had reduced fetal viability. The levels of antibodies reactive with SPRASA in 204 fertile and 202 infertile couples were elevated in 3 infertile but no fertile women. Together, these results indicate that SPRASA has a role in female fertility.Full Tex