Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling
Cryptorchidism, or undescended testis, is a common male genital anomaly of unclear etiology. Hormonal stimulation of the developing fetal gubernaculum by testicular androgens and insulin-like 3 (INSL3) is required for testicular descent. In studies of the orl fetal rat, one of several reported strai...
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| Format: | Article |
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Society for the Study of Reproduction
2014
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| Online Access: | https://eprints.nottingham.ac.uk/41429/ |
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| author | Barthold, Julia S. Robbins, Alan Wang, Yanping Pugarelli, Joan Mateson, Abigail Anand-Ivell, Ravinder Ivell, Richard McCahan, Suzanne M. Akins, Robert E., Jr. |
| author_facet | Barthold, Julia S. Robbins, Alan Wang, Yanping Pugarelli, Joan Mateson, Abigail Anand-Ivell, Ravinder Ivell, Richard McCahan, Suzanne M. Akins, Robert E., Jr. |
| author_sort | Barthold, Julia S. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Cryptorchidism, or undescended testis, is a common male genital anomaly of unclear etiology. Hormonal stimulation of the developing fetal gubernaculum by testicular androgens and insulin-like 3 (INSL3) is required for testicular descent. In studies of the orl fetal rat, one of several reported strains with inherited cryptorchidism, we studied hormone levels, gene expression in intact and hormone-stimulated gubernaculum, and imaging of the developing cremaster muscle facilitated by a tissue clearing protocol to further characterize development of the orl gubernaculum. Abnormal localization of the inverted gubernaculum was visible soon after birth. In the orl fetus, testicular testosterone, gubernacular androgen-responsive transcript levels, and muscle-specific gene expression were reduced. However, the in vitro transcriptional response of the orl gubernaculum to androgen was largely comparable to wild type (wt). In contrast, increases in serum INSL3, gubernacular INSL3-responsive transcript levels, expression of the INSL3 receptor, Rxfp2, and the response of the orl gubernaculum to INSL3 in vitro all suggest enhanced activation of INSL3/RXFP2 signaling in the orl rat. However, DNA sequence analysis did not identify functional variants in orl Insl3. Finally, combined analysis of the present and previous studies of the orl transcriptome confirmed altered expression of muscle and cellular motility genes, and whole mount imaging revealed aberrant muscle pattern formation in the orl fetal gubernaculum. The nature and prevalence of developmental muscle defects in the orl gubernaculum are consistent with the cryptorchid phenotype in this strain. These data suggest impaired androgen and enhanced INSL3 signaling in the orl fetus accompanied by defective cremaster muscle development. |
| first_indexed | 2025-11-14T19:45:19Z |
| format | Article |
| id | nottingham-41429 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:45:19Z |
| publishDate | 2014 |
| publisher | Society for the Study of Reproduction |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-414292020-05-04T16:49:55Z https://eprints.nottingham.ac.uk/41429/ Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling Barthold, Julia S. Robbins, Alan Wang, Yanping Pugarelli, Joan Mateson, Abigail Anand-Ivell, Ravinder Ivell, Richard McCahan, Suzanne M. Akins, Robert E., Jr. Cryptorchidism, or undescended testis, is a common male genital anomaly of unclear etiology. Hormonal stimulation of the developing fetal gubernaculum by testicular androgens and insulin-like 3 (INSL3) is required for testicular descent. In studies of the orl fetal rat, one of several reported strains with inherited cryptorchidism, we studied hormone levels, gene expression in intact and hormone-stimulated gubernaculum, and imaging of the developing cremaster muscle facilitated by a tissue clearing protocol to further characterize development of the orl gubernaculum. Abnormal localization of the inverted gubernaculum was visible soon after birth. In the orl fetus, testicular testosterone, gubernacular androgen-responsive transcript levels, and muscle-specific gene expression were reduced. However, the in vitro transcriptional response of the orl gubernaculum to androgen was largely comparable to wild type (wt). In contrast, increases in serum INSL3, gubernacular INSL3-responsive transcript levels, expression of the INSL3 receptor, Rxfp2, and the response of the orl gubernaculum to INSL3 in vitro all suggest enhanced activation of INSL3/RXFP2 signaling in the orl rat. However, DNA sequence analysis did not identify functional variants in orl Insl3. Finally, combined analysis of the present and previous studies of the orl transcriptome confirmed altered expression of muscle and cellular motility genes, and whole mount imaging revealed aberrant muscle pattern formation in the orl fetal gubernaculum. The nature and prevalence of developmental muscle defects in the orl gubernaculum are consistent with the cryptorchid phenotype in this strain. These data suggest impaired androgen and enhanced INSL3 signaling in the orl fetus accompanied by defective cremaster muscle development. Society for the Study of Reproduction 2014-08-01 Article PeerReviewed Barthold, Julia S., Robbins, Alan, Wang, Yanping, Pugarelli, Joan, Mateson, Abigail, Anand-Ivell, Ravinder, Ivell, Richard, McCahan, Suzanne M. and Akins, Robert E., Jr. (2014) Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling. Biology of Reproduction, 91 (2). pp. 41-54. ISSN 1529-7268 Androgen receptor cryptorchidism gubernaculum insulin-like 3 male reproductive tract https://academic.oup.com/biolreprod/article/2433948/Cryptorchidism doi:10.1095/biolreprod.114.119560 doi:10.1095/biolreprod.114.119560 |
| spellingShingle | Androgen receptor cryptorchidism gubernaculum insulin-like 3 male reproductive tract Barthold, Julia S. Robbins, Alan Wang, Yanping Pugarelli, Joan Mateson, Abigail Anand-Ivell, Ravinder Ivell, Richard McCahan, Suzanne M. Akins, Robert E., Jr. Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling |
| title | Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling |
| title_full | Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling |
| title_fullStr | Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling |
| title_full_unstemmed | Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling |
| title_short | Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling |
| title_sort | cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling |
| topic | Androgen receptor cryptorchidism gubernaculum insulin-like 3 male reproductive tract |
| url | https://eprints.nottingham.ac.uk/41429/ https://eprints.nottingham.ac.uk/41429/ https://eprints.nottingham.ac.uk/41429/ |