Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

Follicle assembly is the process by which groups or 'nests' of oocytes break down to form primordial follicles. The size of the primordial follicle pool is the major determinant of the reproductive lifespan of a female. Previously, progesterone (P 4 ) has been shown to inhibit follicle assembly, while tumor necrosis factor-a (TNFa) has been shown to promote the apoptosis that is necessary for follicle assembly. The present study examines how TNFa and progesterone interact to regulate primordial follicle assembly. Ovaries were collected from newborn rats and placed in organ culture to examine the actions of P 4 and TNFa. P 4 was found to decrease primordial follicle assembly and increase the percentage of unassembled oocytes both in vitro and in vivo. TNFa treatment did not change the proportion of assembled follicles in cultured ovaries, but blocked the ability of P 4 to inhibit follicle assembly. Microarray analysis of the ovarian transcriptome revealed that progesterone treatment of the ovaries altered the expression of 513 genes with 132 only expressed after P 4 treatment and 16 only expressed in control ovaries. The majority of genes were up-regulated greater than twofold over control, with a small subset of 16 genes down-regulated. Categories of genes affected by P 4 are described including a group of extracellular signaling factors. The progesterone receptors expressed at the time of follicle assembly included the surface membrane progesterone receptors PGRMC1, PGRMC2, and RDA288. The nuclear genomic P 4 receptor was not expressed at appreciable levels. Progesterone increased the expression of several genes (TANK, NFkB, Bcl2l1, and Bcl2l2) involved in a signaling pathway that promotes cell survival and inhibits apoptosis. Observations indicate that P 4 acts through the surface membrane progesterone receptors to regulate primordial follicle assembly, and that TNFa can override the inhibitory actions of P 4 on follicle assembly. A major mechanism involved in the actions of P 4 is an increase in cell survival genes and inhibition of the apoptosis pathway. Observations provide insight into the hormonal regulation of primordial follicle assembly and lead to novel approaches to potentially manipulate follicle assembly and reproductive capacity.

From a histological study of the lesions which develop in the vessels of the human pituitary gland during the first two days after the onset of post-partum necrosis of the anterior lobe, it is concluded that the primary vascular disturbance is a spasm involving the arteries which supply the anterior lobe and the stalk. This arrests the portal blood supply and also the direct arterial blood supply to the lobe, but permits a slight circulation to continue in the stalk. If the spasm is relieved within about an hour the parenchyma suffers only a transient functional damage. If it continues for several hours all the tissues in the anterior lobe are killed and, when blood finally attempts to flow into the dead vessels, stasis and thrombosis occurs. This thrombosis is a secondary phenomenon and is not the cause of the necrosis. Variations in the extent and the duration of the spasm account for the variations in the size of the necrosis; in about half the cases the lesion involves 97 to 99 per cent of the anterior lobe, but the pars tuberalis and a small amount of the pars interloralis always survive. The arterial spasm is certainly related to a severe general circulatory collapse at the time of delivery, but the reason for its very specific localisation to the anterior lobe of the pituitary gland remains obscure.

Level IV-case series.

A case of a solitary pilar leiomyoma of the finger in a 47-year-old female is presented. Although leiomyomas of the hand have been described, they typically originate from the smooth muscle of vascular structures. The present case is a leiomyoma derived from smooth muscle of the arrector pili muscle. This has not been reported in the literature. The lesion was excised, symptomatic improvement was achieved, and there are no signs of recurrence at early follow-up