scholarly journals Genetic variability in equine GDF9 and BMP15 genes in Arabian and Thoroughbred mares

2018 ◽  
Vol 18 (1) ◽  
pp. 39-52 ◽  
Author(s):  
Monika Stefaniuk-Szmukier ◽  
Katarzyna Ropka-Molik ◽  
Agata Zagrajczuk ◽  
Katarzyna Piórkowska ◽  
Tomasz Szmatoła ◽  
...  
Keyword(s):  
Genetic Background ◽  
Potential Role ◽  
Ovarian Tissue ◽  
Transcript Abundance ◽  
Ovulation Rate ◽  
Rt Pcr ◽  
Multiple Ovulation ◽  
Genotype Frequencies ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 15

Abstract In horses, multiple ovulation resulting in implantation of multiple embryos is adverse. However, understanding the mechanisms underlying initiation of multiple ovulation (MO) is advantageous and is related to an increase in efficiency of embryo transfer techniques. It has been postulated that MO may have a genetic background. Two major genes: bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) are considered to play a crucial role in folliculogenesis and controlling the ovulation rate. Thus, the aim of the presented study was to identify the variation within equine BMP15 and GDF9 genes to verify their potential role on spontaneous, repetitive multiple ovulations in mares. In addition, variation screening of investigated genes in population of Thoroughbred and Arabian breeds was performed together with establishment of transcript abundance of BMP15 and GDF9 genes in equine ovarian tissue. Sanger sequencing of Arabian and Thoroughbred mares divided according to ovulation rate, revealed occurrence of 3 SNPs in BMP15 and STS in GDF9 genes. The PCR-RLFP and statistical analysis indicated that none of the genotype frequencies were significant in any breeds and none of them were claimed as functional according to ovulation rate. Furthermore, evaluation of transcript abundance by RT -PCR of both genes in ovarian tissues showed that expression of both genes was similar but GDF9 was significantly expressed in growing follicles with 21-30 mm diameter and in ovarian parenchyma, which suggest their potential role in folliculogenesis.

scholarly journals Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle

Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Jennifer L Juengel ◽  
Norma L Hudson ◽  
Martin Berg ◽  
Keith Hamel ◽  
Peter Smith ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Ovarian Function ◽  
Follicular Development ◽  
Active Immunization ◽  
Ovulation Rate ◽  
Differentiation Factor ◽  
Morphogenetic Protein ◽  
Growth Differentiation Factor 9 ◽  
Bone Morphogenetic Protein 15 ◽  
Ovarian Follicular Development

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.

scholarly journals A Novel Mutation in the Bone Morphogenetic Protein 15 Gene Causing Defective Protein Secretion Is Associated with Both Increased Ovulation Rate and Sterility in Lacaune Sheep

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 393-400 ◽  
Author(s):  
Loys Bodin ◽  
Elisa Di Pasquale ◽  
Stéphane Fabre ◽  
Martine Bontoux ◽  
Philippe Monget ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Novel Mutation ◽  
Ovarian Follicle ◽  
Ovulation Rate ◽  
Receptor Type ◽  
Female Sterility ◽  
Mature Peptide ◽  
Bmp Receptor ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 15

Genetic mutations with major effects on ovulation rate and litter size in sheep were recently identified in three genes belonging to the TGFβ superfamily pathway: the bone morphogenetic protein 15 (BMP15, also known as GDF9b), growth differentiation factor 9 (GDF9), and BMP receptor type IB (also known as activin-like kinase 6). Homozygous BMP15 or GDF9 mutations raise female sterility due to a failure of normal ovarian follicle development, whereas heterozygous animals for BMP15 or GDF9 as well as heterozygous and homozygous animals for BMP receptor type IB show increased ovulation rates. In the present work, a new naturally occurring mutation in the BMP15 gene in the high prolific Lacaune sheep breed is described. The identified variant is a C53Y missense nonconservative substitution leading to the aminoacidic change of a cysteine with a tyrosine in the mature peptide of the protein. As for other mutations found in the same gene, this is associated with an increased ovulation rate and sterility in heterozygous and homozygous animals, respectively. Further in vitro studies showed that the C53Y mutation was responsible for the impairment of the maturation process of the BMP15 protein, resulting in a defective secretion of both the precursor and mature peptide. Overall, our findings confirm the essential role of the BMP15 factor in the ovarian folliculogenesis and control of ovulation rate in sheep.

scholarly journals Genes controlling ovulation rate in sheep

Reproduction ◽  
2001 ◽  
pp. 843-852 ◽  
Author(s):  
GW Montgomery ◽  
SM Galloway ◽  
GH Davis ◽  
KP McNatty
Keyword(s):  
New Zealand ◽  
Recent Progress ◽  
Follicular Development ◽  
Ovulation Rate ◽  
Morphogenetic Protein ◽  
Speed Up ◽  
Follicular Size ◽  
Heterozygous Carriers ◽  
Bone Morphogenetic Protein 15 ◽  
Sites Of Action

Sheep provide a valuable model for studying the genetic control of ovulation rate. Recent progress includes the identification of mutations in BMP15 (bone morphogenetic protein 15) that increase ovulation rate in heterozygous carriers and block follicular development in homozygous carriers. The genes characterized to date appear to act principally within the ovary and result in earlier maturity of granulosa cells and reduced follicular size. There may also be other sites of action, and increased FSH concentrations appear to be important in the expression of the FecB phenotype. A new locus on the X chromosome in New Zealand Coopworth sheep increases ovulation rate by about 0.4 and is maternally imprinted. Results from studies in the Cambridge and Belclare breeds indicate that further genes remain to be characterized. Finding the first mutations leading directly to variation in ovulation rate is likely to speed up the identification and molecular analysis of these other genes. There is still much to learn about follicular development and the control of litter size from genetic models in sheep.

scholarly journals Effects of immunizing ewes against bone morphogenetic protein 15 on their responses to exogenous gonadotrophins to induce multiple ovulations

Reproduction ◽  
2011 ◽  
Vol 142 (4) ◽  
pp. 565-572 ◽  
Author(s):  
Jennifer L Juengel ◽  
Laurel D Quirke ◽  
Stan Lun ◽  
Derek A Heath ◽  
Peter D Johnstone ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Granulosa Cells ◽  
Ovulation Rate ◽  
Keyhole Limpet Haemocyanin ◽  
Treatment Groups ◽  
Morphogenetic Protein ◽  
Water Based ◽  
Bone Morphogenetic Protein 15 ◽  
And Control ◽  
Inactivating Mutation

Sheep with a heterozygous inactivating mutation in the bone morphogenetic protein 15 (BMP15) gene experience an increased ovulation rate during either a natural oestrous cycle or a cycle in which exogenous FSH and eCG (gonadotrophins) are given to induce multiple ovulations. The primary aim of these studies was to determine whether ewes immunised against BMP15 would also show an improved superovulation rate following exogenous gonadotrophin treatment. A secondary aim was to determine the effects of BMP15 immunisation on ovarian follicular characteristics. In most ewes (i.e. >75%) immunised with a BMP15-keyhole limpet haemocyanin peptide in an oil-based adjuvant in order to completely neutralise BMP15 bioactivity, there was no superovulation response to exogenous gonadotrophins. In ewes treated with exogenous gonadotrophins following a BMP15-BSA peptide immunisation in a water-based adjuvant to partially neutralise BMP15 bioactivity, the ovulation rate response was similar to the control superovulation treatment groups. Characterisation of follicular function revealed that the water-based BMP15-immunised animals had fewer non-atretic follicles 2.5–3.5 or >4.5 mm in diameter compared with controls. Basal concentrations of cAMP were higher in granulosa cells from animals immunised against BMP15 than control animals. There were no significant differences in the concentrations of cAMP between granulosa cells from BMP15- and control-immunised animals when given FSH or hCG, although there were differences in the proportions of follicles in different size classes that responded to FSH or hCG. Thus, immunisation against BMP15 may have been causing premature luteinisation and thereby limiting the numbers of follicles recruited for ovulation following treatment with exogenous gonadotrophins.

Heterozygous Inverdale ewes show increased ovulation rate sensitivity to pre-mating nutrition

2011 ◽  
Vol 23 (7) ◽  
pp. 866 ◽  
Author(s):  
K. J. Demmers ◽  
B. Smaill ◽  
G. H. Davis ◽  
K. G. Dodds ◽  
J. L. Juengel
Keyword(s):  
Bone Morphogenetic Protein ◽  
Litter Size ◽  
Rate Sensitivity ◽  
Ovulation Rate ◽  
High Group ◽  
Morphogenetic Protein ◽  
Feed Management ◽  
Proportional Increase ◽  
Ad Libitum ◽  
Bone Morphogenetic Protein 15

This study aimed to determine whether ewes heterozygous (I+) for the Inverdale mutation of the bone morphogenetic protein-15 (BMP15) gene with high natural ovulation rate (OR) show similar sensitivity to nutritional manipulation as non-carriers (++). Increasing pre-mating nutrition results in OR increases in sheep, but whether this effect occurs in ewes with naturally high OR is unknown. Over 2 years, I+ or ++ ewes were given high (ad libitum) or control (maintenance) pasture allowances for 6 weeks prior to mating at a synchronised oestrus, with OR measured 8 days later. The high group increased in weight compared with controls (+5.84 kg; P < 0.01), accompanied by increased OR (+19%; P < 0.01). As well as having higher OR (+45%; P < 0.01), I+ ewes responded to increased feed with a larger proportional increase in OR (+27%; P < 0.01) compared with the response in ++ ewes (+11%; P < 0.05), suggesting an interaction between BMP15 levels and nutritional signals in the follicle to control OR. Although litter size increases only tended to significance (+12%; P = 0.06), extra feed resulted in over 50% of I+ ewes giving birth to more than three lambs, compared with 20–31% of I+ ewes on maintenance rations. This information can guide feed management of prolific Inverdale ewes prior to breeding.

scholarly journals Gonadotrophin-responsiveness of granulosa cells from bone morphogenetic protein 15 heterozygous mutant sheep

Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 545-551 ◽  
Author(s):  
Kenneth P McNatty ◽  
Derek A Heath ◽  
Norma L Hudson ◽  
Stan Lun ◽  
Jennifer L Juengel ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Granulosa Cells ◽  
Antral Follicle ◽  
Human Chorionic Gonadotrophin ◽  
Ovulation Rate ◽  
Wild Type ◽  
Binding Characteristics ◽  
Enhanced Sensitivity ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 15

The aim of this study was to test the hypothesis that the higher ovulation-rate in ewes heterozygous for a mutation in bone morphogenetic protein 15 (BMP15; FecXI; otherwise known as Inverdale or I+ ewes) is due to granulosa cells developing an earlier responsiveness to LH, but not FSH. To address this hypothesis, granulosa cells were recovered from every individual nonatretic antral follicle (>2.5 mm diameter) from I+ and wild-type (++) ewes during anoestrus and the luteal and follicular phases and tested for their responsiveness to FSH and human chorionic gonadotrophin (hCG; a surrogate for LH). For the FSH receptor (FSHR) binding study, granulosa cells were harvested in three separate batches from all antral follicles (≥2.5 mm diameter) from I+ and ++ ewes. Using a highly-purified ovine FSH preparation, no evidence was found to suggest that I+ ewes have a higher ovulation-rate due to enhanced sensitivity of granulosa cells to FSH with respect to cAMP responsiveness or to their FSHR binding characteristics (equilibrium Kd or Bmax). By contrast, a significantly higher proportion of follicles from I+ ewes contained granulosa cells responsive to hCG. The higher proportion was due to cells from more small follicles (i.e. >2.5–4.5 mm diameter) developing a response to hCG. It is concluded that the mutation in the BMP15 gene in I+ ewes leads to an earlier acquisition of LH responsiveness by granulosa cells in a greater proportion of follicles and this accounts for the small but significantly higher ovulation-rate in these animals.

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