Joan Jorgensen, DVM, PhD

Jorgensen Lab

Research Description

My laboratory’s investigations into female and male gonad development are inspired by the quest to understand the fetal basis of sex-specific adult diseases in reproductive endocrinology. Our interest in female gonad development is focused on formation of the unique cellular niche, the follicle, which ensures survival and maturation of the female gamete. We discovered a cluster of homeobox transcription factors that are expressed during ovary development whose disruption results in follicle failure and oocyte death, classic components of premature ovarian insufficiency or failure, a devastating disease in adult females. Our interest in male gonad development is centered on local regulation of androgen synthesis. Defective androgen synthesis or activity during fetal development is emerging as a component of adult male infertility and a component of the testis dysgenesis syndrome that includes a constellation of impacts from urogenital tract malformation, infertility, and gonadal cancers. The major goals of my research have been to discover local cell-cell interactions and molecular mechanisms that are used to establish the nascent gonad environments. It has been established that male and female developmental pathways engage in an ongoing battle of mutual antagonism to maintain sex-specific identity. Therefore, we find it critical to understand the sex-specific cell-cell interactions that depend on both time and geographical space during development to help us understand the potential for adult diseases.

Select References:

1. Brown RM, Wang L, Fu A, Kannan A, Mussar M, Bagchi IC, Jorgensen JS. 2022  Irx3 Promotes Gap Junction Communication Between Uterine Stromal Cells to Regulate Vascularization During Embryo Implantation. Biol Reprod. doi: 10.1093/biolre/ioac015. PMID: 35138358. https://academic.oup.com/biolreprod/advance-article/doi/10.1093/biolre/ioac015/6524244
2. Kothandapani A, Jefcoate CR, Jorgensen JS. 2021  Cholesterol contributes to male sex differentiation through its developmental role in androgen synthesis and hedgehog signaling. Endocrinology. 162:bqab066. PMID: 33784378. https://academic.oup.com/endo/advance-article/doi/10.1210/endocr/bqab066/620469
3. Fu A, Koth ML, Brown RM, Shaw SA, Wang L, Krentz KJ, Zhang X, Hui CC, Jorgensen JS. 2020 IRX3 and IRX5 Collaborate During Ovarian Development and Follicle Formation to Establish Responsive Granulosa Cells in the Adult Mouse. Biol Reprod. 103(3):620-629. doi: 10.1093/biolre/ioaa100. PMID: 32507881. https://academic.oup.com/biolreprod/article/103/3/620/5854345
4. Kothandapani A, Lewis SR, Muszynski JL, Zacharski A, Krellwitz K, Baines A, Winske S, Vezina CM, Kaftanovskaya EM, Agoulnik A, Merton EM, Cohn MJ, Jorgensen JS. 2020 GLI3 Resides at the Intersection of Hedgehog and Androgen Action to Promote Male Sex Differentiation. PLoS Genetics. 16(6):e1008810. doi: 10.1371/journal.pgen.1008810. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008810 PMID: 32497091.
   https://news.wisc.edu/forming-genitals-in-boys-requires-complex-dance-between-genes-and-hormones/
5. Koth ML*, Garcia-Moreno SA*, Novak A, Holthusen KA, Kothandapani A, Jiang K, Taketo MM, Nicol B, Yao HHC, Futtner CR, Maatouk DM, Jorgensen JS. 2020 Canonical Wnt/b-catenin Activity and Differential Epigenetic Marks Direct Sexually Dimorphic Regulation of Irx3 and Irx5 in Developing Mouse Gonads. Development. 147(6): pii: dev183814. *co-first authors. https://dev.biologists.org/content/147/6/dev183814.long PMID: 32108023.