CHANGES IN THECAL BONE MORPHOGENETIC PROTEIN RECEPTOR 2 (BMPR2) mRNA IN DOMINANT AND SUBORDINATE FOLLICLES DURING THE FIRST FOLLICULAR WAVE, AND THE EFFECTS OF BMP4 AND ITS ANTAGONIST, GREMLIN, ON OVARIAN GRANULOSA CELL FUNCTION

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 561-585-Ovarian & Uterine Function II
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-564
Leon J Spicer*, Nicole B Schreiber, Luis F Schutz, Morgan L Totty and Pauline Y Aad
Oklahoma State University, Stillwater, OK
Bone morphogenetic proteins (BMPs) such as BMP4 are members of the TGFβ family of proteins that have been implicated in the autocrine and paracrine regulation of ovarian function via their receptors (i.e., BMPRs), but whether BMPRs change in ovarian cells during selection of the dominant follicle in monotocous mammals such as cattle and humans is unknown.  Thus, experiments were conducted to determine if expression of BMPR2 (one of the main BMP receptors) changes during dominant follicle development or differs between ovarian cell types.  The interaction between BMP4 and gremlin on granulosa cell function in vitro was also evaluated. In Experiment 1, estrous cycles of cattle (n=16) were synchronized with two injections of prostaglandin F (11 days apart).  Cattle were ovariectomized on either day 3 or 6 post-ovulation during dominant follicle selection (as assessed by rectal ultrasonography), and thecal cell RNA was isolated.  Quantitative RT-PCR revealed that thecal BMPR2 mRNA abundance did not (P > 0.10) differ between dominant and subordinate follicles or differ between medium (5-8 mm) and large (8-17 mm) follicles on either day 3 or 6.  However, thecal BMPR2 mRNA tended to decrease between day 3 and 6 (5.5 vs. 3.4 ± 0.7 relative abundance, P < 0.10).  Diameter of the dominant follicle increased from 10.7 to 12.1 ± 0.5 mm between day 3 and 6 while follicular fluid estradiol (82 to 126 ± 11 ng/ml) remained constant.   In Experiment 2, granulosa and theca cells from small (3-6 mm) follicles were collected into six pools and RNA was isolated.  BMPR2 mRNA abundance was 3-fold greater (P < 0.01) in theca than granulosa cells.  In vitro, BMP4 at 3, 10 and 30 ng/ml inhibited (P < 0.05) FSH plus IGF1-induced progesterone and estradiol production by granulosa cells of large (8-22 mm) follicles, whereas only 30 ng/ml BMP4 inhibited estradiol production by granulosa cells of small (1-5 mm) follicles.  BMP4 (3, 10 or 30 ng/ml) had no effect (P > 0.10) on IGF1-induced proliferation of small-follicle granulosa cells but BMP4 at 10 and 30 ng/ml increased (P < 0.05) numbers of large-follicle granulosa cells; gremlin inhibited (P < 0.05) this BMP4-induced increase in cell numbers.  These results indicate that the effects of BMP4 on granulosa cell proliferation and steroidogenesis are more pronounced in large vs. small follicles, but whether these differences in granulosa cell responses are due to differences in BMPR2 mRNA abundance will require further study.

Nothing to Disclose: LJS, NBS, LFS, MLT, PYA

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Sources of Research Support: Oklahoma Agricultural Experiment Station