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Uroplakin 1a Knockout Mice Display Marginal Reduction in Fecundity, Decreased Bacterial Clearance Capacity, and Drastic Changes in the Testicular Transcriptome

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Abstract

Uroplakins (UPKs) form physical and chemical barriers in the bladder and other urinary tract tissues. We previously reported the identification and localization of UPKs in the male reproductive tract of rat. In this study, we characterized Upk1a knockout mice and report a marginal reduction in fecundity associated with significant decrease in sperm count. Upk1a mice had lower bacterial clearance capacity when challenged with uropathogenic Escherichia coli for 1 to 5 days. High-throughput analyses of testicular transcriptome indicated that 1128 genes that are expressed in testis of wild-type mice were completely absent in the knockout, while 2330 genes were found to be expressed only in the testis of knockout mice. Furthermore, differential regulation of 148 (67 upregulated and 81 downregulated) was observed. Gene ontology analyses indicated that processes related to integral components of membrane (plasma membrane), G-protein receptor activity and signaling, olfactory receptor activity and perception of smell, organization of extracellular space/region, immune and inflammatory responses to pathogens, spermatid development, meiotic cell cycle, and formation of synaptonemal complex were affected. Results of this study provide evidence on the possible multi-functional role of Upk1a in male reproductive tract and in other tissues as well.

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Data Availability

All relevant data is available in the manuscript.

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Abbreviations

UPKs:

Uroplakins

UPEC:

Uropathogenic E. coli

RT-PCR:

Reverse transcriptase polymerase chain reaction

DAVID:

Database for Annotation, Visualization and Integrated Discovery

PBS:

Phosphate-buffered saline

STAR:

Spliced Transcripts Alignment to a Reference

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Acknowledgements

We thank the facilities extended by UGC-SAP, UGC-CAS, DBT-CREBB, DST-PURSE, UGC-UPE-II, FIST and IoE programmes at School of Life Sciences, University of Hyderabad. SBM received the junior and senior research fellowship from Department of Biotechnology, Government of India. We thank Dr Aurelie Jory (Lily) and the BLiSC Mouse Genome Engineering Facility, National Centre for Biological Sciences, Bangalore, India, for generating the knockout mice.

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SBM carried out the experimental work. SY conceptualized the ideas, wrote the manuscript and provided the reagents and other facilities.

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Correspondence to Suresh Yenugu.

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All procedures involving animals were conducted using the guidelines for the care and use of laboratory animals and this study was specifically approved by the Institutional Animal Ethics Committee of University of Hyderabad (UH/IAEC/SY/2021–1/20).

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Munipalli, S.B., Yenugu, S. Uroplakin 1a Knockout Mice Display Marginal Reduction in Fecundity, Decreased Bacterial Clearance Capacity, and Drastic Changes in the Testicular Transcriptome. Reprod. Sci. 30, 914–927 (2023). https://doi.org/10.1007/s43032-022-01057-z

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