Can exposure to excess androgen during fetal life increase risk of hepatic disease in male offspring?

  Background
Polycystic ovary syndrome (PCOS) is a common condition. Hyperandrogenaemia characterises PCOS, and is considered an ‘in utero environmental programmer’ of PCOS in female offspring. Male offspring from PCOS patients develop dyslipidaemia (elevated total and LDL-cholesterol, elevated triglycerides), with associated increased health risks. Sheep models of PCOS (androgen excess in utero) have demonstrated that male offspring from such androgen excess pregnancies develop an identical dyslipidaemic profile during adolescence to sons of PCOS patients. In addition, these male sheep have increased hepatic mRNA encoding fibrillar collagen proteins and pro-fibrotic factors such as FGF7 and TGFBI, plus increased circulating COL1A1, 1A3, and 5A1 (unpublished, K. Siemienowicz).
We hypothesise that postnatal male liver fibrosis risk is influenced by androgen exposure in utero.
To test this hypothesis, it is important that enzymes involved in collagen deposition are examined. This research proposes to examine liver expression of genes encoding critical enzymes in collagen deposition (lysyl oxidase (LOX) and pro-collagen-C-proteinase (PCP1) in male offspring from a prenatal androgen excess ovine model, and additionally quantify mRNA for collagen subtypes and pro-fibrotic factors such as TGFbeta. Data produced will guide understanding of the role the prenatal steroidal environment has as regards postnatal health risk of fibrotic liver conditions.
This project is a vactaion scholarship application for an undergraduate student. The work entailed, in addition to providing cutting edge experience for the student applicant, also extends the project I am curently employed to research. The duration is 2 months, from mid June until mid-August.

  • Start Date:

    17 June 2019

  • End Date:

    9 August 2019

  • Activity Type:

    Externally Funded Research

  • Funder:

    Society for Reproduction and Fertility

  • Value:

    £3000

Project Team