Group Jaric

The group has two main focuses: 1) exploring the link between stress, female reproductive health, and psychiatric disorders, and 2) developing evidence-based guidelines to enhance the current sex as a biological variable (SABV) initiative in rodent research, thereby improving its translational validity.

We use mouse models and integrate a multidisciplinary approach that brings together a diverse range of tools and methodologies. Our work combines behavioral testing, comprehensive hormonal profiling, classical molecular techniques, qualitative and quantitative histological analyses, and cutting-edge multi-omics approaches—including epigenomics, genomics, and transcriptomics—alongside advanced computational methods.

Endometriosis is a common gynecological disorder affecting up to 15% of women of reproductive age and 50% of those experiencing infertility. While hallmark symptoms such as severe chronic pelvic pain, debilitating menstrual pain, and fatigue are well recognized, emerging evidence suggests a potential link between endometriosis and depression. Our research seeks to elucidate this connection using a translationally relevant mouse model. Specifically, we aim to determine whether depression in individuals with endometriosis arises from the disease itself, the hormonal therapies used as first-line treatment, or a combination of both, and to identify the underlying molecular mechanisms. By doing so, we aim to identify the affected molecular pathways, laying the foundation for future research into their pharmacological modulation and the development of targeted treatments for depression in endometriosis patients.

Hormonal contraceptives are among the most commonly prescribed classes of drugs in the world. Despite their prevalent use for both contraceptive and a wide range of non-contraceptive purposes (such as reducing dysmenorrhea and menorrhagia, managing acne, regulating menstrual cycles, and treating endometriosis and polycystic ovary syndrome), relatively little is known about their impact on the brain and behavior. We are interested in investigating whether oral contraceptive use poses a specific risk of developing mood disorders. Additionally, in light of the recent rise in sex- and gender-related variables being studied in neuroscience, driven by the NIH's Sex as a Biological Variable (SABV) initiative, we will investigate whether the use of oral contraceptives influences the ability to detect sex differences.

For decades, female subjects have been neglected in rodent research, leading to oversights in crucial sex differences, translational failures, and the consequential waste and/or suffering of animals used for inconclusive research. In response, major funders now mandate the inclusion of sex as a biological variable (SABV) in all animal experiments. However, including females prompts consideration of accounting for sex hormone fluctuation, a crucial determinant of female health outcomes. Despite the known impact of sex hormones, which vary significantly across the rodent estrous cycle (similarly to the human menstrual cycle), on a range of biological functions, this variable is largely ignored due to practical limitations. These include potential animal stress during smearing, time-consuming procedures, the lack of standardized training sets for estrous cycle determination, resulting in inconsistent classification and hindering reproducibility. Our project aims to: i) promote a minimally invasive method for estrous cycle determination established in our laboratory that combines tunnel handling and vaginal lavage; ii) develop an automated user-friendly method for estrous cycle stage determination using image analysis by deep learning AI. This approach facilitates rapid estrous cycle staging, enhancing investigators' ability to consider endocrine states in rodent studies, improving data interpretability, and advancing our understanding of sex differences.

As a strong advocate for the inclusion of Sex as a Biological Variable (SABV) in animal study designs, Ivana Jaric organized the first symposium on SABV in basic and preclinical rodent research in 2022 at the University of Bern. Following the success of the inaugural symposium and the subsequent event in 2024, we are excited to continue this biannual tradition at the University of Zurich in 2026. Stay tuned for more information. This international symposium is dedicated to raising awareness of the importance of the SABV initiative and providing evidence-based guidance on integrating SABV into research  practices effectively. The event features lectures by internationally renowned experts from various disciplines, presenting the latest evidence on how sex influences biological processes across molecular, cellular, and organismal levels. SABV 2024 - abstract book