The Role of Bone Morphogenetic Protein 4 in Ovarian Function and Diseases

Author(s):  
Dongyong Yang ◽  
Xiao Yang ◽  
Fangfang Dai ◽  
Yanqing Wang ◽  
Yi Yang ◽  
...  
Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2807-2815 ◽  
Author(s):  
Heather E. McMahon ◽  
Osamu Hashimoto ◽  
Pamela L. Mellon ◽  
Shunichi Shimasaki

Whereas mutations in the bmp15 gene cause infertility in ewes and women due to defects in folliculogenesis, most defects in female mice lacking bone morphogenetic protein (BMP)-15 are confined to the ovulation process, supportive of the observation that functional mouse BMP-15 is barely detected in oocytes in vivo until after the LH surge. In addition, the mouse BMP-15 proprotein is not processed into the functional mature protein in transfected cells. However, a chimeric protein consisting of the human proregion, human cleavage site, and mouse mature region (termed hhmBMP-15) is processed and the mature protein secreted. To study the role of BMP-15 in folliculogenesis, we generated transgenic mice overexpressing hhmBMP-15, exclusively in oocytes during folliculogenesis and confirmed the overexpression of mouse BMP-15 mature protein. Immature transgenic mice exhibited accelerated follicle growth with decreased primary follicles and an increase in secondary follicles. Granulosa cells of immature mice displayed an increased mitotic index and decreased FSH receptor mRNA expression. Adult mice had normal litter sizes but an increased number of atretic antral follicles. Interestingly, aging mice exhibited an early onset of acyclicity marked by increased diestrus length and early occurrence of constant diestrus. These findings indicate the role of BMP-15 in vivo in promoting follicle growth and preventing follicle maturation, resulting in an early decline in the ovarian reserve of transgenic mice. Therefore, the lack of mouse BMP-15 during early folliculogenesis in the wild-type mice may be relevant to their polyovulatory nature as well as the preservation of ovarian function as the mice age.


2021 ◽  
pp. 108769
Author(s):  
Huicong Hu ◽  
Shurong Wang ◽  
Yuxi He ◽  
Sitong Shen ◽  
Boyuan Yao ◽  
...  

2012 ◽  
Vol 227 (6) ◽  
pp. 2595-2604 ◽  
Author(s):  
Rachana Sainger ◽  
Juan B. Grau ◽  
Emanuela Branchetti ◽  
Paolo Poggio ◽  
William F. Seefried ◽  
...  

2007 ◽  
Vol 49 (9) ◽  
pp. 711-719 ◽  
Author(s):  
Yasuhiro Omata ◽  
Yasuhiro Nojima ◽  
Satomi Nakayama ◽  
Hitoshi Okamoto ◽  
Harukazu Nakamura ◽  
...  

2007 ◽  
Vol 65 (3) ◽  
pp. 501-507 ◽  
Author(s):  
Il-Hyuk Chung ◽  
Pill-Hoon Choung ◽  
Hyun-Jeong Ryu ◽  
Young-Ho Kang ◽  
Han-Wool Choung ◽  
...  

2005 ◽  
Vol 17 (9) ◽  
pp. 89
Author(s):  
P. S. Tanwar ◽  
J. R. McFarlane

Bone morphogenetic proteins (BMPs) were first identified on the basis of their bone inducing capacity, and later shown to be members of the transforming growth factor β (TGF β) super family. Nilsson et al.1 studied the effect of BMP-4 on follicular development in rat ovaries and found that the addition of BMP-4 to whole ovary cultures led to more numbers of developing primary follicles but less numbers of primordial follicles. Their studies indicate that BMP-4 acts as a transition factor for the conversion of primordial follicles to primary follicles. To test this hypothesis in-vivo, we conducted passive immunization studies against BMP-4 in prepubertal female mice. The mice were divided in to four groups (n = 5), and given daily SC injections of the following treatment: anti BMP-4 (50μg), PMSG (10 IU) (pregnant mare serum gonadotropin) with and without anti BMP-4 (0.5 mg/mL) and PBS for 3 days. All experimentation was approved by animal ethics committee, University of New England, Armidale, NSW. On the fourth day the mice were killed and the ovaries removed and weighed. The mice treated with anti BMP-4 had significantly smaller ovaries (4.1 ± 0.4 mg) than the control group (8.6 ± 0.9 mg). PMSG stimulated ovarian weight (21.0 ± 1.2 mg) but anti BMP-4 (23.2 ± 1.3 mg) did not significantly affect the weight of the stimulated ovaries. This data confirms BMP-4 is important in ovarian function; however, it is unclear whether this effect is on the ovary directly or via FSH. (1)Nilsson, E. E., Skinner, M.K. (2003). Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biology of Reproduction 69, 1265–1272.


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