Protease genes were identified that exhibited increased mRNA levels before and immediately after rupture of the naturally selected, dominant follicle of rhesus macaques at specific intervals after an ovulatory stimulus. Quantitative real-time PCR validation revealed increased mRNA levels for matrix metalloproteinase (MMP1, MMP9, MMP10, and MMP19) and a disintegrin and metalloproteinase with thrombospondin-like repeats (ADAMTS1, ADAMTS4, ADAMTS9, and ADAMTS15) family members, the cysteine protease cathepsin L (CTSL), the serine protease urokinase-type plasminogen activator (PLAU), and the aspartic acid protease pepsinogen 5 (PGA5). With the exception of MMP9, ADAMTS1, and PGA5, mRNA levels for all other up-regulated proteases increased significantly (P Ͻ 0.05) 12 h after an ovulatory human chorionic gonadotropin (hCG) bolus. MMP1, ADAMTS1, CTSL; PLAU; and PGA5 also exhibited a secondary increase in mRNA levels in 36-h postovulatory follicles. To further determine metalloproteinase involvement in ovulation, vehicle (n ϭ 4) or metalloproteinase inhibitor (GM6001, 0.5 g/follicle, n ϭ 8) was injected into the preovulatory follicle at the time of hCG administration. Of the eight GM6001-injected follicles, none displayed typical stigmata indicative of ovulation at 72 h after hCG; whereas all four vehicle-injected follicles ovulated. No significant differences in mean luteal progesterone levels or luteal phase length occurred between the two groups. Subsequent histological analysis revealed that vehicle-injected follicles ruptured, whereas GM6001-injected follicles did not, as evidenced by an intact stroma and trapped oocytes (n ϭ 3). These findings demonstrate metalloproteinases are critical for follicle rupture in primates, and blocking their activity would serve as a novel, nonhormonal means to achieve contraception. (Endocrinology 152: 3963-3974, 2011) A fter the midcycle LH surge, processes critical for the release of the oocyte from the preovulatory follicle are initiated. The release of the oocyte from the follicle requires highly coordinated events that include the degradation of type IV collagen, laminin, and fibronectin that forms the basement membrane surrounding the follicle as well as the degradation of type I collagen within the follicle wall at the site of rupture (1-5). The degradation and cellular reorganization that takes place also allows for the invasion of newly forming blood vessels into the mural granulosa layer of the follicle (6). Such a high degree of extracellular matrix (ECM) remodeling and cellular reorganization is associated with increased gelatinase, collagenase, and serine protease activities (1). Furthermore, proteolytic activities are required within the follicle to ensure significant expansion of the intercellular space be-

Individuals with 22q11.2 deletion syndrome (22qDS) have increased risk for psychiatric disorders. However, while medical geneticists self-report discussing psychiatric features of 22qDS with families (though often only when the child is older), most parents of children with 22qDS report receiving information about the psychiatric manifestations of 22qDS from non-medical sources. In an attempt to reconcile these previous findings, we sought to objectively determine the frequency with which medical geneticists discuss the potential psychiatric manifestations of 22qDS: (i) in letters to referring physicians and (ii) with families, and to explore plans for follow-up. We abstracted data from charts of patients with 22qDS who were referred to a single medical genetics center between January 1, 2000 and December 31, 2012. Psychiatric disorders were discussed in consult letters to referring physicians for n = 57 (46%) of the 125 patients who met inclusion criteria-making them less frequently discussed than all other features of 22qDS. Despite exhaustive review of charts, the content of discussions with families was typically unclear. Follow-up in medical genetics was suggested for 50 people but only 18 (36%) of these patients returned. Disclosure of psychiatric features of 22qDS to families is necessary so that psychiatric disorders can be identified in time for early intervention to be implemented to achieve better prognosis for those affected. These empiric data offer some explanation as to why psychiatric services are underused by individuals with 22qDS.

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