Language
English
Publication Date
12-1-2022
Journal
Development
DOI
10.1242/dev.201093
PMID
36448532
PMCID
PMC10112923
PubMedCentral® Posted Date
11-30-2022
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Female, Male, Humans, Mice, Animals, Gubernaculum, Cryptorchidism, Fertility, Infertility, Spermatogonia, Mice, Knockout, Wnt4 Protein, Cryptorchidism, Infertility, WNT4, Gubernaculum, SOX9, Undescended testis
Published Open-Access
yes
Recommended Citation
Seth, Abhishek; Bournat, Juan C; Medina-Martinez, Olga; et al., "Loss of WNT4 in the Gubernaculum Causes Unilateral Cryptorchidism and Fertility Defects" (2022). Faculty and Staff Publications. 4817.
https://digitalcommons.library.tmc.edu/baylor_docs/4817
Included in
Health Services Research Commons, Medical Molecular Biology Commons, Medical Specialties Commons, Virology Commons