PMID:17933795

Citation	Yoshida, N, Amanai, M, Fukui, T, Kajikawa, E, Brahmajosyula, M, Iwahori, A, Nakano, Y, Shoji, S, Diebold, J, Hessel, H, Huss, R and Perry, AC (2007) Broad, ectopic expression of the sperm protein PLCZ1 induces parthenogenesis and ovarian tumours in mice. Development 134:3941-52
Abstract	Mammalian metaphase II (mII) exit and embryogenesis are induced at fertilisation by a signal thought to come from the sperm protein, phospholipase C-zeta (PLCZ1). Meiotic progression can also be triggered without sperm, as in parthenogenesis, although the classic mouse in vivo parthenogenetic model, LT/Sv, fails in meiosis I owing to an unknown molecular etiology. Here, we dissect PLCZ1 specificity and function in vivo and address its ability to interfere with maternal meiotic exit. Wild-type mouse Plcz1 expression was restricted to post-pubertal testes and the brains of both sexes, with region-specifying elements mapping to a 4.1 kb Plcz1 promoter fragment. When broad ectopic PLCZ1 expression was forced in independent transgenic lines, they initially appeared healthy. Their oocytes underwent unperturbed meiotic maturation to mII but subsequently exhibited autonomous intracellular free calcium oscillations, second polar body extrusion, pronucleus formation and parthenogenetic development. Transfer of transgenic cumulus cell nuclei into wild-type oocytes induced activation and development, demonstrating a direct effect of PLCZ1 analogous to fertilisation. Whereas Plcz1 transgenic males remained largely asymptomatic, females developed abdominal swellings caused by benign ovarian teratomas that were under-represented for paternally- and placentally-expressed transcripts. Plcz1 was not overexpressed in the ovaries of LT/Sv or in human germline ovarian tumours. The narrow spectrum of PLCZ1 activity indicates that it is modulated by tissue-restricted accessory factors. This work characterises a novel model in which parthenogenesis and tumourigenesis follow full meiotic maturation and are linked to fertilisation by PLCZ1.
Links	PubMed Online version:10.1242/dev.007930
Keywords	Animals; Base Sequence; Cell Transformation, Neoplastic; Cells, Cultured; Female; Gene Expression Regulation; Humans; Male; Meiosis; Mice; Mice, Transgenic; Molecular Sequence Data; Myeloid-Lymphoid Leukemia Protein/metabolism; Oocytes/cytology; Oocytes/metabolism; Ovarian Neoplasms/genetics; Ovarian Neoplasms/metabolism; Ovarian Neoplasms/pathology; Parthenogenesis; Phosphoinositide Phospholipase C/chemistry; Phosphoinositide Phospholipase C/genetics; Phosphoinositide Phospholipase C/metabolism; Sensitivity and Specificity; Spermatozoa/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PLCZ1		GO:0071695: anatomical structure maturation	ECO:0000314:		P		Figure 2 shows that PLCZ1 does not interfere with meiotic progression and that most oocytes establish mII with rPLCZ1.	complete CACAO 6442

References

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