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Title: Crybb2 deficiency impairs fertility in female mice

Highlights: • Crybb2 deletion impaired female fertility. • Crybb2 deletion dramatically affected the production of reproduction-related hormones and hormone response. • Crybb2 deletion impaired follicular development and inhibited the proliferation of granulosa cells. • Crybb2 deletion promoted follicular atresia and apoptosis in granulosa cells. - 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{sup −/−}) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2{sup −/−} 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{sup −/−} 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{sup −/−} female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of femalemore » Crybb2{sup −/−} 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{sup −/−} 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.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ; ; ;  [1] ;  [6] ;  [1]
  1. Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)
  2. Aviation Medical Evaluation and Training Center of Airforce in Dalian, Dalian, Liaoning Province 116013 (China)
  3. (China)
  4. Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062 (China)
  5. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)
  6. Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)
Publication Date:
OSTI Identifier:
22416780
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 453; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; BRAIN; CELL CYCLE; CELL PROLIFERATION; COMPARATIVE EVALUATIONS; ESTROGENS; ESTROUS CYCLE; FEMALES; FERTILITY; GENES; MICE; OVARIES; PROGESTERONE; PROTEINS; REPRODUCTION; RETINA