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Proctor, Elizabeth (2025) Pollutant impact on the postnatal ovine testis: utilising a sheep model to explore multi-generational effects. MRes thesis, University of Nottingham.

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Abstract

In-utero exposure to environmental chemicals is frequently associated with reproductive disorders and reduced fertility. Due to the complexity of real-life mixtures of environmental chemicals, studies utilising models with environmentally relevant concentrations of chemicals are vital.

This study employed immunohistochemistry and qPCR to examine the effects of exposure to a mixture of environmental chemicals present in biosolids at the gross, cellular and molecular

levels in 8-week-old male lambs, across the two subsequent generations (i.e., F1 and F2)

when exposure was limited to the F0 ewes’ pregnancy ensuring all exposure was only in-utero.

In exposed F1 male lambs, testis weight and body weight were both significantly reduced. F2

lambs sired by F1 exposed lambs had greater testis weight and body weights. Histologically,

in the F1s there was no significant difference in mean Sertoli cell numbers and though there

was a noticeable decline in the staining of Leydig cell marker CYP17A1 this was not

statistically significant. In the F2 generation no change in Sertoli cell number was observed,

however there was a notable decrease in CYP17A1 staining in the Biosolids group indicating

a reduction in Leydig cell population. At the molecular level, in the F1 testis, there was a

significant increase in the relative expression of Hexokinase-1 (HK1), an kinase which

phosphorylates glucose in the first step of glycolysis, and a significant decrease in the relative

expression of Calcium and Integrin Binding protein 1 (CIB1) a binding protein thought to be

involved in the proliferation and survival of germ cells. Whilst in the F2 lamb testis, only the

relative expression of CUG-BP, Elav-like family 1 (CELF1) was altered.

Reductions in Sertoli cell and Leydig cell populations have previously been observed at the

foetal level. The lack of significant differences seen in somatic testicular cell populations in this

study in 8-week-old F1 lambs and in other studies in adult rams suggests that during the first

8-weeks of post-natal development there is a degree of compensation. Decreased CYP17A1

staining in the F2 testis potentially highlights a multigenerational effect of gestational exposure

to the biosolids mixture. Overall, this study’s findings suggest the effects of low-level

gestational exposure to environmental chemicals on somatic testicular cells may be corrected

in the pre-pubescent period in the F1 generation. However, some effects may persist into the

F2 generation potentially causing adverse outcomes on adult fertility.

Item Type:	Thesis (University of Nottingham only) (MRes)
Supervisors:	Sinclair, Kevin Lea, Richard
Keywords:	In-utero exposure; Environmental chemicals; Reproductive disorders; Animal models; Fertility
Subjects:	Q Science > QP Physiology
Faculties/Schools:	UK Campuses > Faculty of Science > School of Biosciences
Item ID:	81553
Depositing User:	Proctor, Elizabeth
Date Deposited:	31 Dec 2025 04:40
Last Modified:	31 Dec 2025 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/81553

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