Brainwork in the ovary: kisspeptin and BDNF signaling converge to ensure oocyte survival.

摘要: Premature ovarian failure [now increasingly termed premature insufficiency (POI)] is the loss of function and consequently fertility with estrogen deficiency before age 40 years affects 1% women. In some women, specific causes can be found,suchasevidenceofautoimmunefolliculardamage, chromosome abnormalities, premutations in FMR1 gene or iatrogenic damage such as past exposure to chemotherapyorradiotherapy.Inamajorityofwomen,however,nospecificcauseisfound.Therehavebeenextensive searchesformutationsingenesknowntohavekeyrolesin physiological regulation development function, but these have been identified only rarely, perhaps exception transcription factor NOBOX oogeneis homeobox, which may account for a larger proportion cases than other single-gene mutations (1). Genome-wide association studies also provided insight limited direct clinical relevancethusfarinunderstandingthisrelativelycommon condition. current issue this journal, two new converging pathways regulating follicle oocyte survival are described, both causing POI phenotypes mice. These combined work groups led by Sergio Ojeda Manuel Tena-Sempere, thus bringing together expertise neurotrophin kisspeptin biology intriguing results that shed light on granulosa cell (4, 5). The identification key regulator reproductive decade ago (2) has renaissance interest neuroendocrinology, elaborating upstream GnRH secretion. critical control reproduction at hypothalamiclevelbykisspeptinhasovershadowedandindeed complicates any attempts explore role intraovarian kisspeptin. Previous demonstrated kisspeptin-1 receptor expressed severalcelltypesintheovaryofseveralrodentspeciesand humans, evidence intrafollicular involvement process ovulation (3). present study, akisspeptinreceptorhaplo-insufficiencymodelrevealeda progressive all classes follicles within ovary infertility, was complete 48 weeks (4). animals were not gonadotropin deficient indeed showed expected late rise FSH characteristic failure. ovaries appeared normal young age, fewer ovulations detected 16 thereafter progressivelossofantralandsubsequentlypreantralfollicles. keeping reduced ovulatory weeks, litter size hypomorphs older sterile. necessity signaling further explored 1 nullmice.Becauseoftheirprofoundhypogonadotropism, they treated priming protocol, despite this, atretic early antral no large corpora lutea.AprolongedGnRHplusgonadotropinprimingprotocol did support null animals, released significantly oocytes wild-type females. potential mechanism involved phenotype accompanying paper, indicates remarkablesynergybetweenkisspeptinandneurotrophin necessary