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Title: The hedgehog system in ovarian follicles of cattle selected for twin ovulations and births: evidence of a link between the IGF and hedgehog systems

item AAD, PAULINE - Oklahoma State University
item Echternkamp, Sherrill
item Sypherd, David - Dave
item SCHREIBER, NICOLE - Oklahoma State University
item SPICER, LEON - Oklahoma State University

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/17/2012
Publication Date: 10/1/2012
Publication URL:
Citation: Aad, P.Y., Echternkamp, S.E., Sypherd, D.D., Schreiber, N.B., Spicer, L.J. 2012. The hedgehog system in ovarian follicles of cattle selected for twin ovulations and births: evidence of a link between the IGF and hedgehog systems. Biology of Reproduction. 87(4):79.

Interpretive Summary: The major cause of reproductive inefficiency in cattle is failure to become pregnant. Previous research indicated that cows having increased numbers of antral follicles in their ovaries were more fertile. The hedgehog signaling pathway has been identified as a system of substances (i.e., morphogens) that control basic developmental processes during embryogenesis. Included in these developmental processes are the formation of the female ovary, multiplication of the germ cells (eggs), as well as modulation of ovarian functions and oocyte maturation during the estrous cycle. Objective of the current study was to identify the role(s) of the hedgehog signaling pathway in regulating follicle development and selection of the ovulatory follicle during the bovine estrous cycle. Results provide the first evidence for an association between gene expression for Indian hedgehog and its receptor and the growth and development of small and large healthy follicles during the bovine estrous cycle. Evidence for a contribution of the hedgehog signaling pathway to increased ovarian activity in Twinner cows was inconclusive. Bovine females are born with their life-time supply of eggs; consequently, treatments to enhance expression of the hedgehog signaling pathway during embryogenesis could provide a mechanism to increase follicle numbers and fertility in cattle.

Technical Abstract: Hedgehog signaling is involved in regulation of ovarian function in Drosophila but its role in regulating mammalian ovarian folliculogenesis is less clear. Therefore, gene expression of Indian hedgehog (IHH) and its type 1 receptor, patched 1 (PTCH1), were quantified in bovine granulosa (GC) or theca (TC) cells of small (1-5 mm) antral follicles by in situ hybridization and of large (5-17 mm) antral follicles by real-time RT-PCR from ovaries of cyclic cows selected (Twinner) and unselected (Control) for twin ovulations. Expression of IHH mRNA was localized to GC and cumulus cells, whereas PTCH1 mRNA was greater in TC than in GC. E2-active vs. E2-inactive follicles had a greater abundance of mRNA for IHH in GC and PTCH1 in TC from small and large follicles. Abundance of IHH mRNA in GC of large or small follicles was not affected by cow genotype, but TC PTCH1 mRNA was less in large E2-active (E-A) follicles of Twinners. In vitro E2 increased IHH mRNA in FSH- and IGF1-treated GC, and LH, IGF1 and BMP4 treatments alone decreased PTCH1 mRNA in TC, but GDF9 and activin had no effect. For the first time, functional status of ovarian follicles was associated with differences in hedgehog signaling between GC and TC. We hypothesize that as follicles grow and develop, increased free IGF1 may suppress production of IHH by GC and PTCH1 by TC, and these effects are regulated in a paracrine way by E2 and other intra- and extra-gonadal factors.