Expression and biological effects of bone morphogenetic protein-15 in the hen ovary

The bone morphogenetic protein 15 (Bmp15) and growth differentiation factor 9 (Gdf9) genes are two members of the transforming growth factor-β superfamily. In mammals, these genes are known to be specifically expressed in oocytes and to be essential for female fertility. However, potential ovarian roles of BMPs remain unexplored in birds. The aim of the present work was to study for the first time the expression of Bmp15 in the hen ovary, to compare its expression pattern with that of Gdf9, and then to investigate the effects of BMP15 on granulosa cell (GC) proliferation and steroidogenesis. We found that chicken Bmp15 and Gdf9 genes were preferentially expressed in the ovary. We showed using in situ hybridization that Bmp15 and Gdf9 mRNAs were specifically localized in oocytes of all ovarian follicles examined. We also demonstrated using real-time quantitative RT-PCR that Bmp15 and Gdf9 expression was maintained during hierarchical follicular maturation in the gerrminal disc region and then progressively declined after ovulation. BMP15 was able to activate Smad1 (mothers against decapentaplegichomolog1) signaling pathway in hen GCs. Moreover, we showed a strong inhibitory effect of BMP15 on gonadotropin-induced progesterone production in hen GCs. This inhibitory effect was associated with a decrease in steroidogenic acute regulatory protein (STAR) level. Taken together, our results suggest that BMP15 may have a key role in the female fertility of birds.

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Effects of bone morphogenetic protein 15 (BMP15) knockdown on porcine testis morphology and spermatogenesis

Reproduction Fertility and Development ◽

10.1071/rd20056 ◽

2020 ◽

Vol 32 (11) ◽

pp. 999

Author(s):

Tao Tang ◽

Qiyuan Lin ◽

Yufeng Qin ◽

Xinyu Liang ◽

Yang Guo ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Transforming Growth Factor ◽

Biological Function ◽

Transforming Growth Factor Β ◽

Reproductive Capacity ◽

Ovary Development ◽

Sperm Viability ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

Bone morphogenetic protein 15 (BMP15) is a member of the transforming growth factor-β (TGFB) superfamily that plays an essential role in mammalian ovary development, oocyte maturation and litter size. However, little is known regarding the expression pattern and biological function of BMP15 in male gonads. In this study we established, for the first time, a transgenic pig model with BMP15 constitutively knocked down by short hairpin (sh) RNA. The transgenic boars were fertile, but sperm viability was decreased. Further analysis of the TGFB/SMAD pathway and markers of reproductive capacity, namely androgen receptor and protamine 2, failed to identify any differentially expressed genes. These results indicate that, in the pig, the biological function of BMP15 in the development of male gonads is not as crucial as in ovary development. However, the role of BMP15 in sperm viability requires further investigation. This study provides new insights into the role of BMP15 in male pig reproduction.

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Efficient generation of bone morphogenetic protein 15-edited Yorkshire pigs using CRISPR/Cas9†

Biology of Reproduction ◽

10.1093/biolre/ioaa138 ◽

2020 ◽

Vol 103 (5) ◽

pp. 1054-1068

Author(s):

Xuan Shi ◽

Tao Tang ◽

Qiyuan Lin ◽

Hongbo Liu ◽

Yufeng Qin ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Transforming Growth Factor ◽

Follicular Development ◽

Female Fertility ◽

Efficient Generation ◽

Morphogenetic Protein ◽

Yorkshire Pigs ◽

Bone Morphogenetic Protein 15 ◽

Ovarian Follicular Development

Abstract Bone morphogenetic protein 15 (BMP15), a member of the transforming growth factor beta superfamily, plays an essential role in ovarian follicular development in mono-ovulatory mammalian species. Studies using a biallelic knockout mouse model revealed that BMP15 potentially has just a minimal impact on female fertility and ovarian follicular development in polyovulatory species. In contrast, our previous study demonstrated that in vivo knockdown of BMP15 significantly affected porcine female fertility, as evidenced by the dysplastic ovaries containing significantly decreased numbers of follicles and an increased number of abnormal follicles. This finding implied that BMP15 plays an important role in the regulation of female fertility and ovarian follicular development in polyovulatory species. To further investigate the regulatory role of BMP15 in porcine ovarian and follicular development, here, we describe the efficient generation of BMP15-edited Yorkshire pigs using CRISPR/Cas9. Using artificial insemination experiments, we found that the biallelically edited gilts were all infertile, regardless of different genotypes. One monoallelically edited gilt #4 (Δ66 bp/WT) was fertile and could deliver offspring with a litter size comparable to that of wild-type gilts. Further analysis established that the infertility of biallelically edited gilts was caused by the arrest of follicular development at preantral stages, with formation of numerous structurally abnormal follicles, resulting in streaky ovaries and the absence of obvious estrous cycles. Our results strongly suggest that the role of BMP15 in nonrodent polyovulatory species may be as important as that in mono-ovulatory species.

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