Rare bird species points to new treatment for dangerous fertility disorder
Scientists discovered why estrildid finches resist ovarian hyperstimulation syndrome despite carrying a genetic mutation that triggers the condition in humans. By studying the birds' natural defense mechanism, researchers identified a drug target—a hormone receptor antagonist—that could prevent this serious complication in fertility treatments, potentially expanding access to safe IVF.
Originaltitel: FSHR and LHR functional compensation reveals the mechanism and treatment of Ovarian Hyperstimulation Syndrome
Gain-of-function mutations in the human follicle-stimulating hormone receptor (FSHR) cause spontaneous ovarian hyperstimulation syndrome (OHSS), a serious reproductive disorder. However, the molecular physiology and treatment options for OHSS remain elusive. Notably, estrildid finches naturally carry an FSHR variant (Thr449Ala) analogous to the pathogenic mutation in humans yet are resistant to OHSS. Here we show that this resistance stems from significantly reduced luteinizing hormone receptor expression in estrildid ovarian granulosa cells. Furthermore, treatment with the luteinizing hormone receptor antagonist alleviates OHSS symptoms in mouse models. Single-cell RNA transcriptomic reveals functional compensation of the two receptors to regulate estrogen production and vascular permeability, resembling the adaptive mechanisms observed in estrildid finches. Our study unravels the molecular mechanism underlying the physiological adaptation of estrildid ovaries to high FSHR constitutive activity and is a example of how the concept of Darwinian Medicine could be exploited to identify novel drug targets for ovarian hyperstimulation syndrome treatment. Mutations in the follicle-stimulating hormone receptor (FSHR) cause spontaneous ovarian hyperstimulation syndrome (OHSS). Here, the authors report that estrildid finches naturally carry an analogous pathogenic mutation found in patients but avoid the syndrome by lowering a related receptor’s activity. Blocking this receptor successfully treats OHSS in mice.