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Indian Hedgehog, But Not Histidine Decarboxylase or Amphiregulin, Is a Progesterone-Regulated Uterine Gene in Hamsters

Divisions of Reproductive and Developmental Biology (A.K., X.W., T.D., Q.Z., B.C.P.) and Neonatology (J.R.), Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2678; and Department of Molecular and Cellular Biology (F.J.D.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Bibhash C. Paria, Division of Reproductive and Developmental Biology, D4124 Medical Center North, 1161 21st Avenue South, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2678. E-mail: bc.paria{at}vanderbilt.edu.

Implantation occurs only in the progesterone (P₄)-primed uterus in the majority of species, but little effort has been given to identify P₄-mediated molecules in these species. Using hamsters as a model for P₄-dependent implantation and three well-known uterine receptivity-associated P₄-regulated genes, Indian hedgehog (Ihh), histidine decarboxylase (Hdc), and amphiregulin (Areg), in mice that require ovarian estrogen for uterine receptivity and implantation, our strategy aimed to determine whether P₄ regulates uterine expression of these genes in hamsters and whether the event- and cell-specific uterine expression patterns of these genes during the periimplantation period in hamsters follow similarly with their patterns in mice. We report here that P₄-mediated Ihh signaling is important for uterine receptivity and implantation in hamsters because uterine epithelial Ihh expression was regulated by P₄ and its expression patterns during the periimplantation period of hamsters closely follow its pattern in mice. In contrast, we noted no hormonal regulation of Hdc and Areg in the hamster uterus. However, this did not diminish their importance in hamsters because their expression patterns and functions are event and cell specific during the periimplantation period: whereas Hdc was expressed exclusively in d 4 uterine glands and regulated by the blastocyst, Areg was expressed on the decidual area adjacent to the embryo from d 5 onward and involved in stromal cell proliferation. We conclude that similarities and dissimilarities exist in uterine expression pattern of implantation-related genes, including hormonal regulation and their event-specific importance.

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