Common mechanisms of physiological and pathological rupture events in biology: novel insights into mammalian ovulation and beyond

Abstract

Ovulation is a cyclical biological rupture event fundamental to fertilisation and endocrine function. During this process, the somatic support cells that surround the germ cell undergo a remodelling process that culminates in breakdown of the follicle wall and release of a mature egg. Ovulation is driven by known proteolytic and inflammatory pathways as well as structural alterations to the follicle vasculature and the fluid‐filled antral cavity. Ovulation is one of several types of systematic remodelling that occur in the human body that can be described as rupture. Although ovulation is a physiological form of rupture, other types of rupture occur in the human body which can be pathological, physiological, or both. In this review, we use intracranial aneurysms and chorioamniotic membrane rupture as examples of rupture events that are pathological or both pathological and physiological, respectively, and compare these to the rupture process central to ovulation. Specifically, we compared existing transcriptomic profiles, immune cell functions, vascular modifications, and biomechanical forces to identify common processes that are conserved between rupture events. In our transcriptomic analysis, we found 12 differentially expressed genes in common among two different ovulation data sets and one intracranial aneurysm data set. We also found three genes that were differentially expressed in common for both ovulation data sets and one chorioamniotic membrane rupture data set. Combining analysis of all three data sets identified two genes (Angptl4 and Pfkfb4) that were upregulated across rupture systems. Some of the identified genes, such as Rgs2, Adam8, and Lox, have been characterised in multiple rupture contexts, including ovulation. Others, such as Glul, Baz1a, and Ddx3x, have not yet been characterised in the context of ovulation and warrant further investigation as potential novel regulators. We also identified overlapping functions of mast cells, macrophages, and T cells in the process of rupture. Each of these rupture systems share local vasoconstriction around the rupture site, smooth muscle contractions away from the site of rupture, and fluid shear forces that initially increase and then decrease to predispose one specific region to rupture. Experimental techniques developed to study these structural and biomechanical changes that underlie rupture, such as patient‐derived microfluidic models and spatiotemporal transcriptomic analyses, have not yet been comprehensively translated to the study of ovulation. Review of the existing knowledge, transcriptomic data, and experimental techniques from studies of rupture in other biological systems yields a better understanding of the physiology of ovulation and identifies avenues for novel studies of ovulation with techniques and targets from the study of vascular biology and parturition.

Granulosa cell-layer stiffening prevents the granulosa cells from escaping the post-ovulatory follicle

“…We propose that the increased rigidity it imparts to the GC-layer is key. During ovulation, contractile activity and ECM proteolysis facilitate the release of the cumulus-oocyte complex (COC) from the rupture site [15]. However, we observed in Movie 7 that the rupture site is smaller than the size of the COC, resulting in deformation upon exit.…”

Zearalenone exposure differentially affects the ovarian proteome in pre-pubertal gilts during thermal neutral and heat stress conditions

“…In fetal ovaries, exposure to dexamethasone increased FKBP5 ( Poulain et al, 2012 ), and overexpression of FKBP5 was associated with chemoresistance in ovarian cancer cells ( Sun et al, 2014 ), suggesting that ovarian FKBP5 is involved in the ovarian response to xenobiotic exposure. DDX3X was increased by ZEN in HS gilt ovaries and is involved with cell survival and cell cycle control in embryonic development ( Li et al, 2014 ) and is also identified as being a potential regulator of ovulation ( Zaniker et al, 2023 ). As an indicator of ZEN-induced oxidative stress in gilt ovaries during HS, MGST1 is increased in oocytes from endometriosis patients ( Ferrero et al, 2019 ), and is increased by antioxidant treatment of PCOS in rats ( Zhou et al, 2021 ).…”