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1 April 2009 B-Vitamin and Homocysteine Status Determines Ovarian Response to Gonadotropin Treatment in Sheep
Raji Kanakkaparambil, Ravinder Singh, Dongfang Li, Robert Webb, Kevin D. Sinclair
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Maternal B-vitamin status and homocysteinemia can affect fertility and pregnancy establishment, although the direct effects on ovarian follicle and oocyte development are not known. We report on the effects of restricting the supply of vitamin B12 and methionine from the diet of mature female sheep on ovarian folliculogenesis following follicle-stimulating hormone (FSH) stimulation. The study was split into three batches and involved 76 animals. Surprisingly, the number of growing, estrogen-active antral follicles following FSH treatment was enhanced (P = 0.005) following this dietary intervention. This increase occurred even in the presence of modest live-weight loss (batch 1 only) and depressed plasma insulin concentrations, suggesting a breakdown in the regulation of follicular responsiveness to FSH. This dietary intervention also increased plasma homocysteine concentrations. Physiological concentrations of homocysteine increased granulosa cell proliferation (P < 0.001), estradiol production (P = 0.05), and FSHR transcript expression (P = 0.017) during culture. Transcript levels for growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes from treated ewes were increased (P < 0.05) in the first two batches. Furthermore, regression of BMP receptor 2 (BMPR2) transcript expression and diet on follicle number revealed a significant interaction (P = 0.01); BMPR2 transcript expression was associated with follicle number only in vitamin B12/methionine-restricted animals. Because FSHR transcript expression also was positively (P = 0.007) related to follicle number, the effects of diet may have arisen through enhanced FSH and BMP signaling. Although this remains to be confirmed, the data support an intraovarian impact of vitamin B12/methionine-deficient diets.

Raji Kanakkaparambil, Ravinder Singh, Dongfang Li, Robert Webb, and Kevin D. Sinclair "B-Vitamin and Homocysteine Status Determines Ovarian Response to Gonadotropin Treatment in Sheep," Biology of Reproduction 80(4), 743-752, (1 April 2009).
Received: 23 July 2008; Accepted: 1 November 2008; Published: 1 April 2009
follicle-stimulating hormone
follicle-stimulating hormone receptor
follicular development
granulosa cells
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