020. Oocyte signalling molecules and their effects on reproduction in ruminants

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 in sheep, 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 (i.e. +0.6 to +5.0) than their wild-type contemporaries. In contrast, those homozygous for any of the aforementioned BMP15 or GDF9 mutations are sterile due to abnormal follicular development from the primary stage of growth. In bovine and ovine ovaries, GDF9 is expressed exclusively in oocytes throughout follicular growth from the primordial stage of development, whereas in sheep BMP15 is expressed exclusively in oocytes from the primary stage: no data for BMP15 are available for the cow. In vitro, ovine GDF9 (oGDF9) has no effect on ³H-thymidine incorporation by either bovine or ovine granulosa cells, whereas oBMP15 has modest (1.2 to 1.6-fold; P < 0.05) stimulatory effects. GDF9 or BMP15 alone inhibited progesterone production by bovine granulosa cells, whereas with ovine cells only GDF9 was inhibitory. The effects of GDF9 and BMP15 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. For example, immunisation of ewes with a BMP15 peptide in a water based adjuvant has led to a 25% increase 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, that in vivo manipulation of these oocyte signalling molecules provides a new approach to managing the fertility of ruminants.