Regulation of transcripts encoding ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs-1) and progesterone receptor by human chorionic gonadotropin in equine preovulatory follicles

Abstract

One member of a new family of metalloproteinases, a disintegrin and metalloproteinase with thrombospondin-like motifs-1 (ADAMTS-1), has been found to be expressed and hormonally induced in granulosa cells of ovulating rodent follicles. Furthermore, the targeted disruption of the ADAMTS-1 gene resulted in ovarian defects associated with severely impaired fertility. While these data demonstrate the importance of ADAMTS-1 in rodent ovarian physiology, the potential role of ADAMTS-1 in the ovulatory process of monoovulatory species remains unknown. The objectives of this study were to clone the equine ADAMTS-1 primary transcript and to study its regulation during human chorionic gonadotropin (hCG)-induced ovulation. A 3573 bp follicular cDNA library clone was isolated and found to encode a nearly complete, highly conserved ADAMTS-1 homologue. Real-time RT-PCR analysis detected this transcript in diverse tissues, including previously unreported sites of ADAMTS-1 expression such as the male reproductive tract, the follicular theca interna and the mature corpus luteum. The tissue distribution of the progesterone receptor (PR), a known regulator of ADAMTS-1 expression in rodent preovulatory follicles, was found to overlap that of ADAMTS-1 in some tissues. A study of the regulation of follicular ADAMTS-1 and PR mRNAs during the hCG-induced ovulatory process revealed distinct patterns of regulation in granulosa cells and in theca interna. In granulosa cells, ADAMTS-1 mRNA was found to be induced at 12 h post-hCG (P<0·05), followed by a return to basal levels by 30 h and a re-increase at 33-39 h (P<0·05). A concomitant increase in PR mRNA (P<0·05) was observed at 12 h post-hCG. In theca interna, abundant ADAMTS-1 mRNA was detected at all timepoints, and levels increased transiently at 33 h post-hCG (P<0·05), whereas no significant change was observed in PR mRNA.Together, these data demonstrate for the first time the hormonally regulated ovarian expression of ADAMTS-1 in a monoovulatory species, and identify a novel biphasic regulation of ADAMTS-1 in granulosa cells and a regulated expression in theca interna that were not previously observed in rodents.

Gene expression profiling of bovine preovulatory follicles: gonadotropin surge and prostanoid-dependent up-regulation of genes potentially linked to the ovulatory process

“…Experimental evidence supports a potential involvement of ADAMTS family members in follicular growth and the ovulatory process (Espey et al 2000, Richards et al 2002,Boerboom et al 2003, Madan et al 2003, Richards 2005, Brown et al 2006. Preovulatory regulation of ADAMTS family members in mice has also been reported (Richards 2005).…”

ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary

“…Decreased number of implantation sites was also reported in ADAMTS-1 null mice (Shindo et al 2000, Mittaz et al 2004. ADAMTS-1 mRNA expression is induced in the granulosa cells of the preovulatory follicles after administration of luteinizing hormone (LH) , Boerboom et al 2003, and is sustained in a progesterone-dependent manner . The ADAMTS-1 protein increases after an LH surge and is localized in the cumulus-oocyte complex (COC) of the preovulatory follicles .…”

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

“…In disorders of PR, which controls expression of ADAMTS1, ovulation and fertility problems are observed. Ovulation does not occur successfully and fertility rates are reduced (7,22). ADAMTS1 has critical roles in the degradation of versican, expansion of COC formation, ovulation and angiogenesis.…”

“…Family members of this group are divided into various subgroups according to their tasks in the ECM (Figure 1). ADAMTS1 (METH-1), which was identified for the first time in colon adenocarcinoma, is associated with inflammation (5) and shows anti-angiogenic properties with ADAMTS8 (METH-2) (6,7). Especially in the physiology of ovulation, there is interest in these proteases.…”