Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.
Highlights
Polycystic ovary syndrome (PCOS) is a leading cause of female infertility, affecting 5–10% of reproductive-aged women [1,2]
As a result of such studies, a mouse model of PCOS was later developed using chronic prepubertal administration of DHEA in the BALB/cJ strain [11]. It is unclear whether this genetic background is required for DHEA induction of a PCOS-like state in mice, or whether this treatment can be applied to other, more commonly used mouse strains
We addressed four issues: 1) whether DHEA treatment triggers a PCOS-like reproductive and metabolic state in C57Bl/6J mice, 2) whether reproductive impairments are influenced by the genetic background, 3) whether DHEA treatment more effectively induces the metabolic traits associated with PCOS in C57BL/6J mice, and 4) whether candidate genes with strain-specific variants, association with PCOS, or involvement with steroidogenesis and gluconeogenesis are involved in phenotypic differences
Summary
Polycystic ovary syndrome (PCOS) is a leading cause of female infertility, affecting 5–10% of reproductive-aged women [1,2]. We reasoned that differences in genetic background might influence the development of a PCOS-like reproductive and metabolic state in mice. Limited information exists regarding whether genetic factors contribute to susceptibility in mouse models of PCOS. As a result of such studies, a mouse model of PCOS was later developed using chronic prepubertal administration of DHEA in the BALB/cJ strain [11]. It is unclear whether this genetic background is required for DHEA induction of a PCOS-like state in mice, or whether this treatment can be applied to other, more commonly used mouse strains
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