Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Mutations in the leptin receptor gene associated with delayed onset of puberty are also associated with decreased ovulation and lambing rates in prolific Davisdale sheep

Jennifer L. Juengel A C , Michelle C. French A , Anne R. O’Connell A , Sara J. Edwards A , Avijit Haldar B , Rudiger Brauning A , Phil A. Farquhar A , Ken G. Dodds A , Susan M. Galloway A , Peter D. Johnstone A and George H. Davis A
+ Author Affiliations
- Author Affiliations

A Animal Productivity, AgResearch Limited, Invermay Agricultural Centre, Puddle Alley, Mosgiel 9092, New Zealand.

B Animal Reproduction Division, ICAR Research Complex for NEH Region, Tripura Centre, Lembucherra-799210, West Tripura, India.

C Corresponding author. Email: jenny.juengel@agresearch.co.nz

Reproduction, Fertility and Development 28(9) 1318-1325 https://doi.org/10.1071/RD14382
Submitted: 9 October 2014  Accepted: 13 January 2015   Published: 18 February 2015

Abstract

The aim of this study was to determine if single nucleotide polymorphisms (SNPs) in the leptin receptor (LEPR) gene associated with delayed onset of puberty are associated with changes in other reproductive traits in adult ewes. The ovulation rate of ewes homozygous for the SNPs was ~15% lower (P < 0.001) than either wild-type or heterozygous ewes. First-service conception rate was also affected, being ~12% lower (P < 0. 01) in ewes homozygous for the LEPR SNPs than their wild-type or heterozygous contemporaries. Partial failure of multiple ovulations was also increased (P < 0.01) in ewes that ovulated three ova that were either heterozygous or homozygous for the mutations. Ewes homozygous for the mutations in LEPR had on average 0.2 fewer lambs at mid-pregnancy and at birth compared with the wild-type or heterozygous ewes (P < 0.01). Thus, mutations in LEPR were strongly associated with poorer reproductive performance in Davisdale ewes, which is likely to be linked to both a reduced number of ova available for fertilisation and an increased number of ewes failing to become pregnant. Increased partial failure of multiple ovulations in ewes with high ovulation rates (i.e. 3 or greater) may also contribute to the poor reproductive performance.

Additional keywords: embryo–fetal survival, litter size, oestrous behaviour, partial failure of multiple ovulation, reproductive efficiency.


References

Chebel, R. C., and Santos, J. E. (2011). Association between leptin single nucleotide polymorphism and reproductive performance of lactating Holstein cows. Anim. Reprod. Sci. 127, 126–134.
Association between leptin single nucleotide polymorphism and reproductive performance of lactating Holstein cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlChs7fM&md5=028e5c8048f10376a93fd0cebb4054d3CAS | 21917388PubMed |

Clempson, A. M., Pollott, G. E., Brickell, J. S., Bourne, N. E., Munce, N., and Wathes, D. C. (2011). Evidence that leptin genotype is associated with fertility, growth and milk production in Holstein cows. J. Dairy Sci. 94, 3618–3628.
Evidence that leptin genotype is associated with fertility, growth and milk production in Holstein cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnvFahsbg%3D&md5=76b2434b2f8fccedcfba2868732878cfCAS | 21700051PubMed |

Demmers, K. J., Smaill, B., Davis, G. H., Dodds, K. G., and Juengel, J. L. (2011). Heterozygous Inverdale ewes show increased ovulation rate sensitivity to pre-mating nutrition. Reprod. Fertil. Dev. 23, 866–875.
Heterozygous Inverdale ewes show increased ovulation rate sensitivity to pre-mating nutrition.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVOrtb7N&md5=644db6666dcaf3c079b70d7e748e992cCAS | 21871206PubMed |

Fabre, S., Pierre, A., Mulsant, P., Bodin, L., Di Pasquale, E., Persani, L., Monget, P., and Monniaux, D. (2006). Regulation of ovulation rate in mammals: contribution of sheep genetic models. Reprod. Biol. Endocrinol. 4, 20.
Regulation of ovulation rate in mammals: contribution of sheep genetic models.Crossref | GoogleScholarGoogle Scholar | 16611365PubMed |

Forcada, F., and Abecia, J. A. (2006). The effect of nutrition on the seasonality of reproduction in ewes. Reprod. Nutr. Dev. 46, 355–365.
The effect of nutrition on the seasonality of reproduction in ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVOnsr3N&md5=d239ef76c71a5296c9a07fa35054d4b5CAS | 16824445PubMed |

Gonzalez-Añover, P., Encinas, T., Sanz, E., Letelier, C. A., Torres-Rovira, L., de Mercado, E., Pallares, P., Sanchez-Sanchez, R., and Gonzalez-Bulnes, A. (2011a). Preovulatory follicle dynamics and ovulatory efficiency in sows with thrifty genotype and leptin resistance due to leptin receptor gene polymorphisms (Iberian pig). Gen. Comp. Endocrinol. 170, 200–206.
Preovulatory follicle dynamics and ovulatory efficiency in sows with thrifty genotype and leptin resistance due to leptin receptor gene polymorphisms (Iberian pig).Crossref | GoogleScholarGoogle Scholar | 20951700PubMed |

Gonzalez-Añover, P., Encinas, T., Torres-Rovira, L., Pallares, P., Muñoz-Frutos, J., Gomez-Izquierdo, E., Sanchez-Sanchez, R., and Gonzalez-Bulnes, A. (2011b). Ovulation rate, embryo mortality and intrauterine growth retardation in obese swine with gene polymorphisms for leptin and melanocortin receptors. Theriogenology 75, 34–41.
Ovulation rate, embryo mortality and intrauterine growth retardation in obese swine with gene polymorphisms for leptin and melanocortin receptors.Crossref | GoogleScholarGoogle Scholar | 20833418PubMed |

Haldar, A., French, M. C., Brauning, R., Edwards, S. J., O’Connell, A. R., Farquhar, P. A., Davis, G. H., Johnstone, P. D., and Juengel, J. L. (2014). Single nucleotide polymorphisms in the LEPR are associated with divergent phenotypes for age at onset of puberty in Davisdale ewes. Biol. Reprod. 90, 33.
Single nucleotide polymorphisms in the LEPR are associated with divergent phenotypes for age at onset of puberty in Davisdale ewes.Crossref | GoogleScholarGoogle Scholar | 24389871PubMed |

Juengel, J. L., O’Connell, A. R., French, M. C., Proctor, L. E., Wheeler, R., Farquhar, P. A., Dodds, K. G., Galloway, S. M., Johnstone, P. D., and Davis, G. H. (2011). Identification of a line of sheep carrying a putative autosomal gene increasing ovulation rate in sheep that does not appear to interact with mutations in the transforming growth factor beta superfamily. Biol. Reprod. 85, 113–120.
Identification of a line of sheep carrying a putative autosomal gene increasing ovulation rate in sheep that does not appear to interact with mutations in the transforming growth factor beta superfamily.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXotFOls7g%3D&md5=40f95547f5b3027af3a747bdbc67d3ddCAS | 21415136PubMed |

Juengel, J., O’Connell, A., Farquhar, P., Johnston, P., and Davis, G. (2012). Evidence for a single gene affecting embryo/fetal survival in the Davisdale flock. Reprod. Domest. Anim. 47, 506.

Juengel, J. L., Davis, G. H., and McNatty, K. P. (2013). Using sheep lines with mutations in single genes to better understand ovarian function. Reproduction 146, R111–R123.
Using sheep lines with mutations in single genes to better understand ovarian function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhs1ygtr7K&md5=149a7e0143d61b6ca91fd4a7bb0be854CAS | 23801782PubMed |

Kelly, R. W., and Allison, A. J. (1976). Measurement of ovulation rate by laparoscopy and effects on reproductive performance. Proc. N.Z. Soc. Anim. Prod. 36, 240–246.

Komisarek, J., and Antkowiak, I. (2007). The relationship between leptin gene polymorphisms and reproductive traits in Jersey cows. Pol. J. Vet. Sci. 10, 193–197.
| 1:CAS:528:DC%2BD1cXjsVCgs7c%3D&md5=49f32b3664c1afc424f84a31ed66cae6CAS | 18198534PubMed |

Kosior-Korzecka, U., and Bobowiec, R. (2003). Changes in the level of endogenous leptin, FSH, 17β-oestradiol and metabolites during lupin-induced increase in ovulation rate in ewes. J. Vet. Med. A Physiol. Pathol. Clin. Med. 50, 343–349.
Changes in the level of endogenous leptin, FSH, 17β-oestradiol and metabolites during lupin-induced increase in ovulation rate in ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXptFSjurY%3D&md5=d00022c2361d233fc5c178f008f0a444CAS | 14633226PubMed |

Kosior-Korzecka, U., Bobowiec, R., and Lipecka, C. (2006). Fasting-induced changes in ovulation rate, plasma leptin, gonadotrophins, GH IGF-I and insulin concentrations during oestrus in ewes. J. Vet. Med. A. Physiol. Pathol. Clin. Med. 53, 5–11.
Fasting-induced changes in ovulation rate, plasma leptin, gonadotrophins, GH IGF-I and insulin concentrations during oestrus in ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xis1art7g%3D&md5=b6725019fc25a5808b758bb3e4722ef2CAS | 16411900PubMed |

Maymó, J. L., Pérez Pérez, A., Gambino, Y., Calvo, J. C., Sánchez-Margalet, V., and Varone, C. L. (2011). Review: leptin gene expression in the placenta – regulation of a key hormone in trophoblast proliferation and survival. Placenta 32, S146–S153.
Review: leptin gene expression in the placenta – regulation of a key hormone in trophoblast proliferation and survival.Crossref | GoogleScholarGoogle Scholar | 21303721PubMed |

Scaramuzzi, R. J., Adams, N. R., Baird, D. T., Campbell, B. K., Downing, J. A., Findlay, J. K., Henderson, K. M., Martin, G. B., McNatty, K. P., McNeilly, A. S., and Tsonis, C. G. (1993). A model for follicle selection and the determination of ovulation rate in the ewe. Reprod. Fertil. Dev. 5, 459–478.
A model for follicle selection and the determination of ovulation rate in the ewe.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXivFSntr4%3D&md5=a5fc7cf5893061fdcf9f6838ec50affcCAS | 8190903PubMed |

Scaramuzzi, R. J., Campbell, B. K., Downing, J. A., Kendall, N. R., Khalid, M., Munoz-Gutierrez, M., and Somchit, A. (2006). A review of the effects of supplementary nutrition in the ewe on the concentrations of reproductive and metabolic hormones and the mechanisms that regulate folliculogenesis and ovulation rate. Reprod. Nutr. Dev. 46, 339–354.
A review of the effects of supplementary nutrition in the ewe on the concentrations of reproductive and metabolic hormones and the mechanisms that regulate folliculogenesis and ovulation rate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVOnsrzF&md5=16d4d9d6130575dbb7ebdba94024a940CAS | 16824444PubMed |

Scaramuzzi, R. J., Baird, D. T., Campbell, B. K., Driancourt, M. A., Dupont, J., Fortune, J. E., Gilchrist, R. B., Martin, G. B., McNatty, K. P., McNeilly, A. S., Monget, P., Monniaux, D., Viñoles, C., and Webb, R. (2011). Regulation of folliculogenesis and the determination of ovulation rate in ruminants. Reprod. Fertil. Dev. 23, 444–467.
Regulation of folliculogenesis and the determination of ovulation rate in ruminants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjt12ntLg%3D&md5=d250734c3e9c9baef1d84ebc61c9998eCAS | 21426863PubMed |

Shorten, P. R., O’Connell, A. R., Demmers, K. J., Edwards, S. J., Cullen, N. G., and Juengel, J. L. (2013). Effect of age, weight and sire on embryo and fetal survival in sheep. J. Anim. Sci. 91, 4641–4653.
Effect of age, weight and sire on embryo and fetal survival in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhs1SqtL3L&md5=906ed4ef52d7b5dff1372e1938baa652CAS | 23942709PubMed |

Viñoles, C., Paganoni, B., Glover, K. M. M., Milton, J. T. B., Blache, D., Blackberry, M. A., and Martin, G. B. (2010). The use of a ‘first-wave’ model to study the effect of nutrition on ovarian follicular dynamics and ovulation rate in the sheep. Reproduction 140, 865–874.
The use of a ‘first-wave’ model to study the effect of nutrition on ovarian follicular dynamics and ovulation rate in the sheep.Crossref | GoogleScholarGoogle Scholar | 21109612PubMed |

Williams, G. L., Amstalden, M., Garcia, M. R., Stanko, R. L., Nizielski, S. E., Morrison, C. D., and Keisler, D. H. (2002). Leptin and its role in the central regulation of reproduction in cattle. Domest. Anim. Endocrinol. 23, 339–349.
Leptin and its role in the central regulation of reproduction in cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xls1Wkurw%3D&md5=41f0f5750bb664cc6bb1fb00c8c35a2bCAS | 12142250PubMed |

Wylie, A. R. (2011). Leptin in farm animals: where are we and where can we go? Animal 5, 246–267.
Leptin in farm animals: where are we and where can we go?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXksFGqtg%3D%3D&md5=dd653f1f782cca20f8a5474e5dddd19fCAS | 22440770PubMed |

Zieba, D. A., Amstalden, M., and Williams, G. L. (2005). Regulatory roles of leptin in reproduction and metabolism: a comparative review. Domest. Anim. Endocrinol. 29, 166–185.
Regulatory roles of leptin in reproduction and metabolism: a comparative review.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXltVehu70%3D&md5=d07bd1ce9e9c8bc39662c80d122421ebCAS | 15927772PubMed |