Bone Morphogenetic Protein 15 Knockdown Inhibits Porcine Ovarian Follicular Development and Ovulation

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are essential for ovarian follicular growth in sheep, whereas only GDF9 is essential in mice suggesting that the roles of these oocyte-derived growth factors differ among species. At present, however, there is only limited information on the action of BMP15 and GDF9 in other species. Thus, the aim of this experiment was to determine the effect of neutralizing GDF9 and/or BMP15in vivoon ovarian follicular development and ovulation rate in cattle through active immunization using the mature regions of the proteins or peptides from the N-terminal area of mature regions. Immunization with the BMP15 peptide, with or without GDF9 peptide, significantly altered (increased or decreased) ovulation rate. In some animals, there were no functional corpora lutea (CL), whereas in others up to four CL were observed. From morphometric examination of the ovaries, immunization with GDF9 and/or BMP15 reduced the level of ovarian follicular development as assessed by a reduced proportion of the ovarian section occupied by antral follicles. In addition, immunization against GDF9 and/or BMP15 peptides reduced follicular size to <25% of that in the controls. In conclusion, immunization against GDF9 and BMP15, alone or together, altered follicular development and ovulation rate in cattle. Thus, as has been observed in sheep, both GDF9 and BMP15 appear to be key regulators of normal follicular development and ovulation rate in cattle.

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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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Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 Are Essential for Ovarian Follicular Development in Sheep1

Biology of Reproduction ◽

10.1095/biolreprod.102.007146 ◽

2002 ◽

Vol 67 (6) ◽

pp. 1777-1789 ◽

Cited By ~ 199

Author(s):

Jennifer L. Juengel ◽

Norma L. Hudson ◽

Derek A. Heath ◽

Peter Smith ◽

Karen L. Reader ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Follicular Development ◽

Differentiation Factor ◽

Morphogenetic Protein ◽

Growth Differentiation Factor 9 ◽

Bone Morphogenetic Protein 15 ◽

Ovarian Follicular Development

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Oocyte Bone Morphogenetic Protein 15, but not Growth Differentiation Factor 9, Is Increased During Gonadotropin-Induced Follicular Development in the Immature Mouse and Is Associated with Cumulus Oophorus Expansion1

Biology of Reproduction ◽

10.1095/biolreprod.106.055574 ◽

2006 ◽

Vol 75 (6) ◽

pp. 836-843 ◽

Cited By ~ 54

Author(s):

Xavier Guéripel ◽

Véronique Brun ◽

Alain Gougeon

Keyword(s):

Bone Morphogenetic Protein ◽

Follicular Development ◽

Cumulus Oophorus ◽

Differentiation Factor ◽

Morphogenetic Protein ◽

Growth Differentiation Factor 9 ◽

Immature Mouse ◽

Bone Morphogenetic Protein 15

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Essential role of Bone morphogenetic protein 15 in porcine ovarian and follicular development and ovulation

10.1101/724096 ◽

2019 ◽

Author(s):

Yufeng Qin ◽

Tao Tang ◽

Wei Li ◽

Zhiguo Liu ◽

Xiaoliang Yang ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Essential Role ◽

Mammalian Species ◽

Critical Role ◽

Follicular Development ◽

Female Fertility ◽

Regulatory Function ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

ABSTRACTBone morphogenetic protein 15 (BMP15) is a multifunctional oocyte-specific secreted factor. It controls female fertility and follicular development in both species-specific and dosage-sensitive manners. Previous studies found that BMP15 played a critical role on follicular development and ovulation rate of mono-ovulatory mammalian species, but has minimal impact on poly-ovulatory mice. However, whether this is true in non-rodent poly-ovulatory species need to be validated. To investigate this question, we generated a BMP15 knockdown pig model. We found that BMP15 knockdown gilts showed markedly reduced fertility accompanied with phenotype of dysplastic ovaries containing significantly declined number of follicles, increased number of abnormal follicles, and abnormally enlarged antral follicles resulting in disordered ovulation. Molecular and transcriptome analysis revealed that knockdown of BMP15 significantly suppressed cell proliferation, differentiation, Fshr expression, leading to premature luteinization and reduced estradiol production in GCs, and simultaneously decreased the quality and meiotic maturation of oocyte. Our results provide in vivo evidences for the essential role of BMP15 in porcine ovarian and follicular development, and new insight into the complicated regulatory function of BMP15 in female fertility of poly-ovulatory species.

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Expression Profiles of the Progesterone Receptor, Cyclooxygenase-2, Growth Differentiation Factor 9, and Bone Morphogenetic Protein 15 Transcripts in the Canine Oviducts during the Oestrous Cycle

Animals ◽

10.3390/ani11020454 ◽

2021 ◽

Vol 11 (2) ◽

pp. 454

Author(s):

Jaime Palomino ◽

Javiera Flores ◽

Georges Ramirez ◽

Victor H. Parraguez ◽

Monica De los Reyes

Keyword(s):

Gene Expression ◽

Bone Morphogenetic Protein ◽

Cyclooxygenase 2 ◽

Oestrous Cycle ◽

Progesterone Concentration ◽

Plasma Progesterone ◽

Morphogenetic Protein ◽

Growth Differentiation Factor 9 ◽

Bone Morphogenetic Protein 15 ◽

Cox 2

The gene expression in the canine oviduct, where oocyte maturation, fertilization, and early embryonic development occur, is still elusive. This study determined the oviductal expression of (PR), cyclooxygenase-2 (COX-2), growth differentiation factor 9 (GDF-9), and bone morphogenetic protein 15 (BMP-15) during the canine oestrous cycle. Samples were collected from bitches at anoestrus (9), proestrus (7), oestrus (8), and dioestrus (11), after routine ovariohysterectomy and the ovarian surface structures and plasma progesterone concentration evaluated the physiological status of each donor. The oviductal cells were isolated and pooled. Total RNA was isolated, and gene expression was assessed by qPCR followed by analysis using the t-test and ANOVA. The PR mRNA increased (P < 0.05) from the anoestrus to dioestrus with the plasma progesterone concentration (r = 0.8). COX-2 mRNA expression was low in the anoestrus and proestrus, and negligible in the oestrus, while it was around 10-fold higher (P < 0.05) in the dioestrus. The GDF-9 mRNA was expressed during all phases of the oestrous cycle and was most abundant (P < 0.05) during oestrus phase. The BMP-15 mRNA decreased (P < 0.05) in the anoestrus and proestrus phases. Thus, the transcripts were differentially expressed in a stage-dependent manner, suggesting the importance of oestrous cycle regulation for successful reproduction in dogs.

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