Fenvalerate Exposure And Polymorphism In Androgen Related Genes Are Associated With Ovarian Follicular Development

PartⅠFenvalerate inhibits the growth of primary cultured rat preantral ovarian follicleFenvalerate is a widely used synthetic pyrethroid insecticide and is reported to disrupt reproductive function in human and animals. However, little is known about its influence on follicular development. In this study, rat preantral follicles were primary cultured to investigate the effects of fenvalerate on follicular survival rate, morphological change, steroid hormone levels and steroidogenesis related gene mRNA expression. Follicles were cultured with 0, 1, 5 and 25μmol/L fenvalerate for 72 h. And then the morphous was assessed by conventional light microscopy, steroid hormones were measured by RIA, and the expressions of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc) were monitored by real-time quantitative PCR analysis. Results showed that fenvalerate inhibited the augmentation of follicular diameters in a dose-dependent manner but did not have detectable effects on follicular survival rates. The level of steroid hormones, such as progesterone, testosterone and estradiol, was inhibited. The inhibition might due to the decreased expression levels of StAR and P450scc. These results suggested that fenvalerate restrained the follicular growth, and inhibited steroidogenesis by reducing StAR and P450scc gene expression, which may further contribute to the fenvalerate-induced reproductive dysfunction.PartⅡAssociation of the HSD17B5 and HSD17B6 gene polymorphism with polycystic ovary syndromeIncreased androgen production is a primary feature of polycystic ovary syndrome (PCOS) and appears to be an inherited trait. Type 5 17βhydroxysteroid dehydrogenase (HSD17B5) and Type 6 17βhydroxysteroid dehydrogenase (HSD17B6) were implicated as candidates for PCOS by previous studies. Our objective was to investigate association between polymorphisms in HSD17B5, HSD17B6 and PCOS in a well characterized cohort. We conducted a case-control association study. Subjects were recruited from reproductive endocrinology clinics; Controls were pregnant women recruited from Nanjing Maternity and Child Health Care Hospital. Participants included 335 women with PCOS and 354 controls. Genotyping occurred at Nanjing Medical University. We assessed HSD17B5, HSD17B6 genotype, PCOS status, and metabolic traits. Results showed that allele distribution for the single-nucleotide polymorphism rs1937845 in HSD17B5 gene was significantly different between PCOS and control subjects (p=0.01). In PCOS subjects, presence of rs1937845 polymorphic allele was associated with increased HOMA-B% (p=0.045), and was related to the increased testosterone, but did not have a significant difference (p=0.053); Presence of rs1937845 polymorphic allele was associated with increased testosterone (p=0.034). Further, we divided PCOS subjects into hyperandrogenism and non-hyperandrogenism, allele distribution for the single-nucleotide polymorphism rs1937845, rs12529 in HSD17B5 gene were significantly different between hyperandrogenism and non-hyperandrogenism PCOS subjects (p=0.007, p=0.005). No association was seen between HSD17B6 and any variables studied. These data suggest that polymorphisms in the HSD17B5 gene are associated with PCOS and key clinical phenotypes of the disorder, and the polymorphisms in the HSD17B6 gene are not associated with PCOS and key clinical phenotypes of the disorder.