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

Victoria University of Wellington, Wellington 6140, New Zealand¹ Mesynthes Ltd, Lower Hutt 5040, New Zealand² AgResearch, Invermay Agricultural Centre, Mosgiel 9053, New Zealand

Correspondence should be addressed to K P McNatty; Email: kenneth.mcnatty{at}vuw.ac.nz

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; FecX^I; 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 K_d or B_max). 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.