Proliferating cell nuclear antigen (PCNA) regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.
Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA), a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer granulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.
Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Bo
B
Xu
Juan
J
Hua
Yuanwei
Y
Zhang
Xiaohua
X
Jiang
Huan
H
Zhang
Tieliang
T
Ma
Wei
W
Zheng
Rui
R
Sun
Wei
W
Shen
Jiahao
J
Sha
Howard J
HJ
Cooke
Qinghua
Q
Shi
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009865:Oocytes / Q000166:cytology*; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism*; D010053:Ovary / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering
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