Meat and Livestock Association Plenary Lecture 2005. Oocyte signalling molecules and their effects on reproduction in ruminants
Kenneth P. McNatty A C D , Stephen Lawrence A , Nigel P. Groome B , Mohammed F. Meerasahib B , Norma L. Hudson A , Lynda Whiting A , Derek A. Heath A and Jennifer L. Juengel AA AgResearch, Wallaceville Animal Research Centre, PO Box 40063, Upper Hutt, New Zealand.
B School of BMS, Oxford Brookes University, Gypsy Lane, Headington, Oxford X3OBP, UK.
C Present address: The School of Biological Sciences, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.
D Corresponding author. Email: kenneth.mcnatty@vuw.ac.nz
Reproduction, Fertility and Development 18(4) 403-412 https://doi.org/10.1071/RD05104
Submitted: 15 September 2005 Accepted: 1 January 2006 Published: 22 March 2006
Abstract
Sheep (Ovis aries) are a highly diverse species, with more than 900 different breeds that vary significantly in their physiological characteristics, including ovulation rate and fecundity. From examination of inherited patterns of ovulation rate, several breeds have been identified with point mutations in two growth factor genes that are expressed in oocytes. Currently, five different point mutations have been identified in the BMP15 (GDF9b) gene and one in GDF9. Animals heterozygous for the GDF9 and/or the BMP15 mutations have higher ovulation rates than their wild-type counterparts. In contrast, those homozygous for any of the aforementioned BMP15 or GDF9 mutations are sterile owing to arrested follicular development. In bovine and ovine ovaries, GDF9 was expressed exclusively in oocytes throughout follicular growth from the primordial stage of development, whereas in sheep BMP15 was expressed exclusively in oocytes from the primary stage: no data for the ontogeny of BMP15 expression are currently available for cattle. In vitro, ovine growth differentiation factor 9 (oGDF9) has no effect on 3H-thymidine incorporation by either bovine or ovine granulosa cells, whereas ovine bone morphogenetic protein 15 (oBMP15) has modest (1.2- to 1.6-fold; P < 0.05) stimulatory effects. Ovine GDF9 or oBMP15 alone inhibited progesterone production by bovine granulosa cells, whereas in ovine cells only oGDF9 was inhibitory. The effects of oGDF9 and oBMP15 together were often cooperative and not always the same as those observed for each factor alone. Active immunisation of ewes with BMP15 and/or GDF9 peptides affected ovarian follicular development and ovulation rate. Depending on the GDF9 and/or BMP15 vaccine formulation, ovulation rate was either increased or suppressed. A primary and single booster immunisation of ewes with a BMP15 peptide in a water-based adjuvant has led to 19–40% increases in lambs born per ewe lambing. Collectively, the evidence suggests that oocyte signalling molecules have profound effects on reproduction in mammals, including rodents, humans and ruminants. Moreover, in vivo manipulation of these oocyte signalling molecules provides new opportunities for the management of the fertility of ruminants.
Extra keywords: activin-like kinase 6, bone morphogenetic protein 15, growth differentiation factor 9, ovary, ovulation rate.
Acknowledgments
The authors thank Adrian Bibby, Andrea Western, Lisa Haydon, Karen Reader, Stan Lun and Peter Smith for technical assistance, Doug Jensen and Daniel Olliver for animal care and management and George Davis and Janet Crawford for helpful suggestions with the manuscript. The authors acknowledge support from the New Zealand Foundation for Research Science and Technology, the Royal Society of New Zealand Marsden Fund and Ovita Limited, Dunedin, New Zealand.
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