I. Uterine 3D morphology and extracellular matrix in establishment and maintenance of pregnancy, II. Search and study of novel genetic and contributing factors critical for male fertility

Infertility is a growing issue in modern society. My research team is focusing on researching factors contributing to female and male fertility. Specifically, the uterine morphogenesis and the role of the extracellular matrix in female fertility and identifying genetic and contributing factors affecting male fertility. The research consists of two major directions (I & II).

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University of Oulu

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Project description

I. Uterine 3D morphology and extracellular matrix in establishment and maintenance of pregnancy

While a healthy and functional uterus is a major organ for successful pregnancy outcomes it does not have a replacement in assisted reproductive technologies. The efficient molecular and cell-to-cell crosstalk between the uterus and an implantation-competent embryo is essential for pregnancy establishment. Inefficient embryo-uterine interactions can result in pregnancy complications such as preeclampsia or pregnancy loss. Despite its central role in establishing a successful pregnancy, the knowledge of prenatal and post-natal uterine development is limited, and the knowledge of 3D morphology and extracellular matrix role is vague. Our research aims to fill in these knowledge gaps and use the know-how in diagnostic method development.

II. Search and study of novel genetic and contributing factors critical for male fertility

Male infertility is largely attributed to genetic, environmental, and physiological factors. There are many still uncharacterized testis-specific genes with potential clinical significance. We use in silico methods and infertile men databases to identify genetic and contributing factors causing male infertility. We carry on in-depth biological and biochemical characterization of testes-enriched genetic factors and define their function and role in male fertility to aid infertile men's diagnostics and possible treatments.

Project results

Selected list of publications

Kazi S, Castañeda JM, Savolainen A, Xu Y, Liu N, Qiao H, Ramirez-Solis R, Nozawa K, Yu Z, Matzuk MM, Prunskaite-Hyyryläinen R. MRNIP interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice. FASEB J. (2022). doi: 10.1096/fj.202101168RR

Monsivais D, Nagashima T, Prunskaite-Hyyryläinen R, Nozawa K, Shimada K, Tang S, Hamor C, Agno J, Chen F, Masand R, Young S, Creighton C, DeMayo F, Ikawa M, Lee S, Matzuk MM. Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis. Nature Communications. (2021) Jun 7; 12(1):3386. doi.org/10.1038/s41467-021-23571-5

Oura S*, Kazi S*, Savolainen A, Nozawa K, Castañeda JM, Yu Z, Miyata H, Matzuk R, Hansen JN, Wachten D, Matzuk MM#, Prunskaite-Hyyryläinen R#. Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility. PlosGenetics. (2020) Aug 12;16(8):e1008954. doi.org/10.1371/journal.pgen.1008954

Prunskaite-Hyyryläinen R, Skovorodkin I, Xu Q, Miinalainen I, Shan J, Vainio SJ. Wnt4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract. Hum Mol Genet. (2016) 25(6):1059-73. doi.org/10.1093/hmg/ddv621

Prunskaite-Hyyryläinen R, Shan J, Railo A, Heinonen KM, Miinalainen I, Yan W, Shen B, Perreault C, Vainio SJ. Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimüllerian hormone expression during oocyte maturation in the female follicle. FASEB J. (2014) 28(4):1568-81.