Testicular Phenotypes of RDHE DKO Mice

Authors

• Aja Slay, University of Alabama at Birmingham

Advisor(s)

Natalia Kedishvili

Committee Member(s)

Kirill Popov
Nabiha Yusuf

School

College of Arts and Sciences

Document Type

Thesis

Department (new version)

Biology

Date of Award

9-9-2024

Abstract

The bioactive form of vitamin A, all-trans-retinoic acid (RA), plays a critical role in cell differentiation, metabolism, and cellular proliferation by regulating gene transcription. RA signaling is critical during embryogenesis to ensure proper development and during adulthood for tissue maintenance. Disruption of the RA signaling pathway induced by vitamin A deficiency and genetic defects in vitamin A metabolizing enzymes results in embryonic malformations. Previous studies implicate the short-chain dehydrogenase/reductase (SDR) family members as important in RA synthesis. Among the SDR family are retinol dehydrogenase epidermal 2 (RDHE2) and RDHE2-similar (RDHE2S)- collectively RDHE. To gain insight into how RDHE influences the vitamin A status, we generated RDHE double knockout mice (DKO). Although RDHE are not expressed in testis postnatally, genetic deletion of RDHE was shown to have an impact on testis. There was a significant decrease of RA in the serum of RDHE DKO mice on a vitamin A deficient diet (VAD), disorganization of seminiferous tubules, lower sperm count, and significant decrease in the number of Sertoli cells in RDHE DKO mice compared to matched WT controls on the same diets. RDHE are expressed in other tissues, including the gastrointestinal tract. Careful examination of RDHE DKO mice revealed gastrointestinal phenotypes that might impair vitamin A absorption. In RDHE DKO mice, there was a significant increase of goblet cells in the jejunum compared to matched WT controls on regular diet (RD), a significant decrease of surface area in the jejunum of DKO mice on VAD compared to matched WT controls, and a significant increase of FITC-dextran levels in the plasma compared to matched WT controls. In summary, studies of RDHE DKO mice suggest that abnormal morphology and function of the gastrointestinal tract may cause poor nutrient absorption. Systemic effects from the deletion of RDHE in the intestines may underlie the testicular phenotypes of RDHE DKO mice.

ProQuest ID

https://proquest.com/docview/3101841806