{"doi":"10.1242/dev.201093","title":"Loss of WNT4 in the gubernaculum causes unilateral cryptorchidism and fertility defects","abstract":"Undescended testis (UDT) affects 6% of male births. Despite surgical correction, some men with unilateral UDT may experience infertility with the contralateral descended testis (CDT) showing no A-dark spermatogonia. To improve our understanding of the etiology of infertility in UDT, we generated a novel murine model of left unilateral UDT. Gubernaculum-specific Wnt4 knockout (KO) mice (Wnt4-cKO) were generated using retinoic acid receptor β2-cre mice and were found to have a smaller left-unilateral UDT. Wnt4-cKO mice with abdominal UDT had an increase in serum follicle-stimulating hormone and luteinizing hormone and an absence of germ cells in the undescended testicle. Wnt4-cKO mice with inguinal UDT had normal hormonal profiles, and 50% of these mice had no sperm in the left epididymis. Wnt4-cKO mice had fertility defects and produced 52% fewer litters and 78% fewer pups than control mice. Wnt4-cKO testes demonstrated increased expression of estrogen receptor α and SOX9, upregulation of female gonadal genes, and a decrease in male gonadal genes in both CDT and UDT. Several WNT4 variants were identified in boys with UDT. The presence of UDT and fertility defects in Wnt4-cKO mice highlights the crucial role of WNT4 in testicular development.","journal":"Development","year":2022,"id":274728,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":528170,"name":"Juan C. Bournat","orcid":null,"position":1,"is_corresponding":false},{"id":922613,"name":"Olga Medina-Martínez","orcid":"0000-0003-3515-9786","position":2,"is_corresponding":false},{"id":733674,"name":"Armando Rivera","orcid":"0000-0001-7076-8566","position":3,"is_corresponding":false},{"id":733673,"name":"Joshua Moore","orcid":"0000-0001-7879-0135","position":4,"is_corresponding":false},{"id":943275,"name":"Hunter Flores","orcid":"0000-0002-7915-0858","position":5,"is_corresponding":false},{"id":15091,"name":"Jill A. Rosenfeld","orcid":"0000-0001-5664-7987","position":6,"is_corresponding":false},{"id":307899,"name":"Liya Hu","orcid":"0000-0002-8340-8911","position":7,"is_corresponding":false},{"id":527346,"name":"Carolina J. Jorgez","orcid":"0000-0001-9203-6331","position":8,"is_corresponding":false},{"id":527345,"name":"Abhishek Seth","orcid":"0000-0002-4071-3588","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-19T00:28:12.324621Z","pmid":"36448532","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}