Fig. 3.

AMH prenatal programing in the pathophysiology of PCOS. Clinical evidence indicates that PCOS mothers maintain high AMH levels from the second gestational trimester to term. Maternal AMH-induced changes in PCOS may rely on central actions that increase GnRH pulsatile release, hence, culminating in high LH pulsatile secretion. Enhanced LH actions in the PCOS ovaries favor ovarian androgen production creating a hyperandrogenic environment. AMH also inhibits maternal placental aromatase expression, which increases testosterone bioavailability in utero. Prenatal and neonatal hyperandrogenism leads to increased excitatory GABAergic appositions to GnRH neurons and to a persistent GnRH neuronal hyperactivity in adulthood. Excitatory innervation of GnRH neurons might be responsible for the increased GnRH–LH pulse frequency observed in PCOS-like animals. These abnormal changes may dictate the neuroendocrine derangements of the adult manifestation of PCOS and may play an important role in the etiology of the disease