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Cell Death Dis

Title:		Seipin deficiency increases chromocenter fragmentation and disrupts acrosome formation leading to male infertility
Author(s):		El Zowalaty AE; Baumann C; Li R; Chen W; De La Fuente R; Ye X;
Address:		"1] Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA [2] Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, USA. Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA. Department of Physiology, Georgia Regents University, Augusta, GA, USA"
Journal Title:		Cell Death Dis
Year:		2015
Volume:		20150716
Issue:		7
Page Number:		e1817 -
DOI:		10.1038/cddis.2015.188
ISSN/ISBN:		2041-4889 (Electronic)
Abstract:		"The Berardinelli-Seip congenital lipodystrophy type 2 (Bscl2, seipin) gene is involved in adipogenesis. Bscl2-/- males were infertile but had normal mating behavior. Both Bscl2-/- cauda epididymis sperm count and sperm motility were ~20xless than control. Bscl2-/- seminiferous tubules had relatively normal presence of spermatogonia and spermatocytes but had reduced spermatids and sperm. Spatiotemporal expression analyses in Bscl2+/+ testes demonstrated prominent Bscl2 transcriptional activity in spermatocytes with a plateau reached around postnatal day 28. Seipin protein localization was most abundant in postmeiotic spermatids, suggesting translational repression of Bscl2 mRNA in spermatocytes. In situ end-labeling plus detected increased spermatid apoptosis in Bscl2-/- testis and annexin V detected increased percentage of positive Bscl2-/- round spermatids compared with control. Immunofluorescence of marker proteins synaptonemal complex proteins 3 and 1 (SYCP3 and SYCP1), and H3K9me3 (histone H3 trimethylated at lysine 9) in germ cell spreads detected normal meiotic chromosome pairing and homologous chromosome synapsis in Bscl2-/- spermatocytes, but significantly increased percentages of round spermatids with chromocenter fragmentation and late spermatids and sperm with chromatin vacuoles, indicating defective chromatin condensation in Bscl2-/- spermatids. Bscl2-/- late spermatids were disorganized within the seminiferous epithelium, despite normal appearance of Sertoli cells detected by vimentin immunofluorescence. Peanut agglutinin staining revealed various abnormalities of acrosomes in Bscl2-/- late spermatids, including the absence, irregular-shaped, and fragmented acrosomes, indicating defective acrosome formation in Bscl2-/- late spermatids, which may affect late spermatid orientation in the seminiferous epithelium. Mitotracker strongly stained the midpiece of control sperm but only very weakly labeled the midpiece of Bscl2-/- sperm, indicating defective mitochondrial activity that most likely contributed to reduced Bscl2-/- sperm motility. These data demonstrate novel roles of seipin in spermatid chromatin integrity, acrosome formation, and mitochondrial activity. Increased spermatid apoptosis, increased chromocenter fragmentation, defective chromatin condensation, abnormal acrosome formation, and defective mitochondrial activity contributed to decreased sperm production and defective sperm that resulted in Bscl2-/- male infertility"
Keywords:		"Acrosome/*pathology Adipogenesis/genetics Animals Apoptosis/genetics Cell Cycle Proteins Chromatin/metabolism DNA-Binding Proteins GTP-Binding Protein gamma Subunits Gene Expression Regulation, Developmental Heterotrimeric GTP-Binding Proteins/biosynthesi;"
Notes:		"MedlineEl Zowalaty, A E Baumann, C Li, R Chen, W De La Fuente, R Ye, X eng R15HD066301/HD/NICHD NIH HHS/ R01 HD042740/HD/NICHD NIH HHS/ R01 HD065939/HD/NICHD NIH HHS/ R01HD065939/HD/NICHD NIH HHS/ R15 HD066301/HD/NICHD NIH HHS/ 2R01HD042740/HD/NICHD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2015/07/17 Cell Death Dis. 2015 Jul 16; 6(7):e1817. doi: 10.1038/cddis.2015.188"