Transcriptomic Profiling of Ovaries in Mice Lacking the Insulin Receptor-Related Receptor
Acid-base homeostasis is a fundamental regulator of ovarian physiology, influencing follicular development, oocyte maturation, and hormone synthesis. Disruption of local pH balance within the ovarian microenvironment can impair steroidogenesis, fertilization, and early embryo viability. The insulin receptor-related receptor (IRR) is a unique member of the insulin receptor's family that functions as a sensor of extracellular alkaline pH, becoming activated when the surrounding environment exceeds pH 7.9. IRR expression is highly tissue-specific, detected primarily in kidney collecting ducts, stomach, specific regions of the brain and the ovary. In mice with a knockout of the insrr gene, which encodes for IRR, urinary bicarbonate secretion in response to alkali loading is impaired. However, its mechanisms of action and physiological significance in non-renal organs, particularly within the female reproductive system, are unknown. To address this issue, we analyzed and compared the ovary transcriptomes of wild-type and insrr knockout mice. We found 141 transcripts with significant changed expression levels in ovary. In the ovary, most of these transcripts are associated with antiviral defense and interferon-signaling pathways, including Oas2, Oas3, Mx2, Irf7, Irf9, Rsad2, Stat1, Stat2, and Isg15. In addition, the expression of two steroidogenic genes, Cyp17a1 and Akr1c18, which are involved in progesterone metabolism, was also affected.