Renata Prunskaite-Hyyryläinen: Reproductive and Molecular Biology
Research group information
Research group description
FERTILITY issues affect about 20% of the global population of reproductive age, with both male and female factors contributing to these cases. In our reproductive and molecular biology laboratory, we aim to understand the molecular cues of fertility to aid diagnostics and treatment of infertile individuals. Our research is divided into male-focused and female-focused studies.
MALE
Male infertility is a prevalent and highly heterogeneous disease for which the underlying causes remain undefined in up to 70% of the cases, indicating a lack of understanding regarding the impact of genetics and the environment on gamete production. This lack of awareness leads to a generic approach to treating patients, and the use of medically assisted reproduction techniques without addressing the root causes.
Our research aims to 1) discover novel genes and mutations compromising fertility in men, 2) characterize male fertility related genes/mutations using cell culture and mouse models, and 3) reveal the biophysical properties of fertility-associated proteins. These studies are applicable in improving infertility diagnostics and drug development.
FEMALE
While fertilization issues can be overcome and embryos generated in vitro with assisted reproductive technologies, the uterus remains the major organ supporting embryo development throughout pregnancy. The uterus has a dynamic environment, regularly undergoing dramatic remodeling in relation to menstrual cycles, pregnancy, post-partum recovery, and menopause. Efficient cell-to-cell crosstalk between a functional uterus and an implantation-competent embryo is essential for pregnancy establishment. Failures in this interaction can lead to recurrent miscarriages or other pregnancy complications. Despite the importance of uterine responsiveness for a successful pregnancy to occur, knowledge of its genetic regulation, uterine 3D morphology, and extracellular matrix remodeling is still insufficient.
In our lab we are specifically interested in 1) uncovering how genetic and metabolic pathologies affect uterine receptivity and hence fertility, 2) examining the role of the extracellular matrix in association with fertility, and 3) characterizing 3D uterine morphology for the discovery of diagnostic clues and methods.
Research Group Members
Renata Prunskaite-Hyyryläinen, PhD, Assistant Professor
Emmi Kapiainen, PhD
Samina Kazi-Prat, Doctoral researcher
Audrey Savolainen, Doctoral researcher
Bianca Sammer, Doctoral researcher
Anna-Liisa Honkimaa, MSc student
Alumni
Célia Tebbakh, MSc thesis (2022-2023)
Philomena Schmid, MSc thesis (2021-2022)
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Publications
Selected publications and summaries
- Savolainen A, Kapiainen E, Ronkainen V-P, Izzi V, Matzuk MM, Monsivais D, Prunskaite-Hyyryläinen R. 3DMOUSEneST: a volumetric, label-free imaging method evaluating embryo-uterine interaction and decidualization efficacy. Development. Development (2024) 151 (16): dev202938. doi: 10.1242/dev.202938.
Mice are widely used in biomedical research to model human fertility issues, but there is a lack of methods to study the very early pregnancy progression in mice. Using higher harmonic generation microscopy, we have developed a cutting-edge 3D imaging method which provides both visual and quantitative means to assess implantation sites in mice. Applicable for studying embryos 1–3 days after implantation, 3DMOUSEneST evaluates decidual fibrillar collagen deposition, decidualization efficacy, embryo growth, and theoretical prediction of early pregnancy success.
- Kazi S, Castañeda J, Savolainen A, Xu Y, Liu N, Qiao H, Ramirez-Solis R, Nozawa K, Yu Z, Matzuk M M, Prunskaite-Hyyryläinen R. MRNIP interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice. FASEB J. (2022) 36(9):e22479. doi: 10.1096/fj.202101168RR
Our study shows that the Mrnip gene is critical for male but not for female fertility. If the Mrnip gene is absent in mice, there is no sperm formation, and the males are infertile. Mrnip acts during early spermatogenesis, specifically in meiosis from mid-pachytene to diplotene. We show that Mrnip protein droplets in the meiocyte nucleus fuse and form a droplet-like structure that interacts with the sex body encapsulating X and Y chromosomes. The absence of the Mrnip function leads to altered meiotic sex chromosome inactivation, ablated sperm formation, and infertility.
- 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 J, DeMayo F J, Ikawa M, Lee S, Matzuk M M. Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis. Nature Communications. (2021) 12(1):3386. doi.org/10.1038/s41467-021-23571-5
Among the specific discoveries presented in this article, the role of our laboratory was to develop a methodology for 3D uterine gland analysis by optical projection tomography (OPT) and multiphoton microscopy. The 3D scans of the entire uterus and single uterine glands showed that uterine gland shape is genetically predisposed and is associated with female fertility. Furthermore, the 3D scan analysis suggests that coiling instead of branching is likely the more common phenotype for uterine glands in non-pregnant mice.
- Oura S*, Kazi S*, Savolainen A, Nozawa K, Castañeda J, Yu Z, Miyata H, Matzuk R M, Hansen J N, Wachten D, Matzuk M M#, Prunskaite-Hyyryläinen R#. Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility. PlosGenetics. (2020) 16(8):e1008954. doi.org/10.1371/journal.pgen.1008954
In this study, we provide insights into the function of a previously uncharacterized Cfap97d1 gene and demonstrate that it is testes-specific gene, which controls the structural integrity of the sperm tail, sperm motility, and fertility in male mice. We remark that based on our work, the CFAP97D1 protein was renamed to Sperm axonemal maintenance protein CFAP97D1 (UniProt Q9DAN9 & B2RV13).