Survival of newborn placental mammals depends on closure of the ductus arteriosus (DA), an arterial connection in the fetus which directs blood away from the pulmonary circulation and towards the placenta where oxygenation occurs. Here we show that morphological changes resulting in closure of the DA in mice are virtually identical to those observed in larger mammals, including humans, and that maintenance of the DA in the open, or patent, state in fetal mice is dependent on prostaglandin synthesis. This requirement is absent in mice lacking the prostaglandin E2 EP4 receptor (EP4(-/-) mice). In EP4(-/-) mice of the 129 strain, remodelling of the DA fails to occur after birth, resulting in a left-to-right shunt of blood and subsequently in death. This suggests that the neonatal drop in prostaglandin E2 that triggers ductal closure is sensed through the EP4 receptor. In contrast, 5% of EP4(-/-) mice of mixed genetic background survive, and selective breeding of these mice leads to a 21% survival rate, suggesting that alleles at other loci can provide an alternative mechanism for ductal closure.

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Medical Center ver the past decade, use of androgen deprivation therapy (ADT) to treat prostate cancer has risen seven-fold, from 9.8% of patients in 1989-1992 to 74.6% in 1991-2001 (1). ADT is used as neoadjuvant and adjuvant treatment with radiation therapy (RT), to treat recurrence following primary treatment with surgery or RT, or when the cancer is in an advanced stage at diagnosis. While ADT has demonstrated survival benefits, it also is associated with increases in metabolic and cardiovascular risks. Men receiving ADT have been shown to develop dyslipidemia, decreased arterial compliance, increased insulin resistance, weight gain with increased visceral fat deposition, decreased bone mineral density, decreased libido and erectile dysfunction, fatigue, cognitive changes and depression (1-12)

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