Renault L, Patiño LC, Magnin F, et al. - Primary ovarian insufficiency (POI) affects nearly 1% of women under 40 years of age and is characterized by the premature depletion of ovarian follicles and raised plasma levels of follicle-stimulating hormone resulting in infertility, researchers here sought to determine and to functionally validate new sequence variants in 2 genes that play a key role in mammalian ovarian function, BMPR1A and BMPR1B  (encoding for bone morphogenic protein receptor), leading to POI. Different in vitro functional experiments were undertaken to establish the effect on bone morphogenic protein (BMP) signaling of BMPR1A and BMPR1B variants, previously identified by whole-exome sequencing on 69 women affected by isolated POI. They observed infertility in mice lacking Bmpr1a in the ovaries and in Bmpr1b-/- mice. Results thereby revealed, for the first time, a correlation between BMPR1A and BMPR1B variants and the origin of POI. BMP signaling impairment through specific BMPR1A and BMPR1B variants is recognized to be a novel pathophysiological mechanism implicated in human POI. BMPR1A and BMPR1B variants are thus suggested as valuable genetic biomarkers of the origin of POI and have clinical utility.