title: Crybb2 deficiency impairs fertility in female mice.
abstract: Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2(-/-)) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2(-/-) mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2(-/-) mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2(-/-) female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2(-/-) mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2(-/-) mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells.
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Aviation Medical Evaluation and Training Center of Airforce in Dalian, Dalian, Liaoning Province 116013, PR China; Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, PR China.
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Xiang
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Tao
authors.affiliation: Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: zhangjj910@163.com.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: wenjieli@pku.org.cn.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D006107:Granulosa Cells / Q000378:metabolism / Q000473:pathology; D007247:Infertility, Female / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology; D011374:Progesterone / Q000096:biosynthesis; D038206:beta-Crystallin B Chain / Q000235:genetics / Q000502:physiology*
chemical_list: D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2; D011374:Progesterone; D004958:Estradiol
keywords: Apoptosis; Beta-B2; Crystallin; Fertility; Granulosa cells