Retinoic acid inhibits rat XY gonad development by blocking mesonephric cell migration and decreasing the number of gonocytes

Hui Li; Kwan Hee Kim

doi:10.1095/biolreprod.103.023135

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Retinoic acid inhibits rat XY gonad development by blocking mesonephric cell migration and decreasing the number of gonocytes

Journal article

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Retinoic acid inhibits rat XY gonad development by blocking mesonephric cell migration and decreasing the number of gonocytes

Hui Li and Kwan Hee Kim

Biology of reproduction, Vol.70(3), pp.687-693

03/2004

DOI: https://doi.org/10.1095/biolreprod.103.023135

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https://hdl.handle.net/2376/117473

PMID: 14613895

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Abstract

Immunohistochemistry

Prenatal Exposure Delayed Effects

Apoptosis - drug effects

Glycoproteins - metabolism

Male

Sertoli Cells - drug effects

Testis - drug effects

Testis - embryology

Sertoli Cells - cytology

Receptors, Retinoic Acid - agonists

Testicular Hormones - metabolism

Anti-Mullerian Hormone

Female

Antineoplastic Agents - pharmacology

Organ Culture Techniques

Tretinoin - pharmacology

Sertoli Cells - metabolism

Testis - cytology

Mesonephros - cytology

Rats

Receptors, Retinoic Acid - antagonists & inhibitors

Rats, Sprague-Dawley

Pregnancy

Cell Movement - drug effects

Mesonephros - drug effects

Animals

Mesonephros - embryology

Cell Differentiation - drug effects

Retinoic Acid Receptor alpha

Vitamin A (also called retinol) and its derivatives, retinoic acids (RAs), are required for postnatal testicular function. Abnormal spermatogenesis is observed in rodents on vitamin A-deficient diets and in retinoic acid receptor alpha (RARalpha) knockout mice. In contrast, RA has an inhibitory effect on the XY gonad development in embryos. To characterize this inhibitory effect of RA, we investigated the cellular events that are required for the XY gonad development, including cell migration from the adjacent mesonephros into the gonad, fetal Sertoli cell differentiation, and survival of gonocytes. In organ cultures of Embryonic Day 13 (E13) XY gonads from rats, all-trans-retinoic acid (tRA) inhibited mesonephric cell migration into the gonad. Moreover, treatment with tRA decreased the expression of Müllerian-inhibiting substance in Sertoli cells and dramatically reduced the number of gonocytes. Increased apoptosis was detected in the XY gonads cultured with tRA, suggesting that the loss of gonocytes could be due to increased apoptosis. In addition, Am580, a synthetic compound that exhibits RARalpha-specific agonistic properties, mimicked the inhibitory effects of tRA on the XY gonad development including mesonephric cell migration and gonocyte survival. Conversely, a RARalpha-selective antagonist, Ro 41-5253, suppressed the inhibitory ability of tRA on the XY gonad development. These results suggest that retinoic acid acting through RARalpha negatively affects fetal Sertoli cell differentiation and gonocyte survival and blocks the migration of mesonephric cells, thereby leading to inhibition of the XY gonad development.

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Title: Retinoic acid inhibits rat XY gonad development by blocking mesonephric cell migration and decreasing the number of gonocytes
Creators: Hui Li - School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, 99164-4234, USA
Kwan Hee Kim
Publication Details: Biology of reproduction, Vol.70(3), pp.687-693
Publisher: United States
Identifiers: 99900547992201842
Language: English
Resource Type: Journal article