Theses and Dissertations

Issuing Body

Mississippi State University

Advisor

Cheng, Wen-Hsing

Committee Member

Zhou, Qian

Committee Member

Nannapaneni, Ramakrishna

Committee Member

Olivier, Alicia

Committee Member

Zhang, Li

Date of Degree

12-10-2021

Document Type

Dissertation - Open Access

Major

Food Science, Nutrition, and Health Promotion

Degree Name

Doctor of Philosophy (Ph.D)

College

College of Agriculture and Life Sciences

Department

Department of Food Science, Nutrition and Health Promotion

Abstract

Low-hierarchy selenoproteins are sensitive to selenium (Se) deficiency and are proposed to confer the protection of body Se against age- and development-related diseases. Selenoprotein H (SELENOH), a low-hierarchy selenoprotein, is greatly downregulated by both dietary Se deficiency and age. To explore physiological roles of SELENOH, Selenoh knockout mice were employed.

Segregation analyses demonstrated reduced frequencies of homozygotes and heterozygotes among the neonates of the breeding combinations of Selenoh+/- males vs. Selenoh+/- or Selenoh-/- females, demonstrating essential roles of SELENOH in embryogenesis. Litter sizes from these two breeding groups were comparable with control, suggesting a role of SELENOH in zygotic but not somatic embryogenesis. By contrast, SELENOH was dispensable for longevity in mice.

Selenoh-/- males showed azoospermia and a 34%-63% reduction in testis mass in the mice. Histological examination and the analyses of stage-specific markers by qRT-PCR indicated that the Selenoh-/- spermatocytes were arrested in the pachytene stage. Furthermore, GPX4 plausibly accounted for some of the Se loss in the testes because the knockout resulted in a 90% decrease in GPX4 mRNA level. Interestingly, the knockout increased the Selenop and Gpx1 mRNA levels by over 2.3- and 1.9-folds, respectively, but decreased the mRNA amount of Selenov by 99.9% in the testes. As a key component of the meiotic cohesion complex to promote sister chromatid cohesion, Rec8 mRNA amount was reduced by 91.1% in the Selenoh-/- testes aged 42 days.

SELENOH knockout did not affect body weight or food intake but resulted in glucose intolerance and insulin resistance in the mice. Additionally, SELENOH knockout reduced the mRNA amounts of Gpx1, Gpx4, and Txnrd1 in the liver and Gpx4 in the skeletal muscle. These findings suggest that SELENOH plays a role in glucose metabolism and regulates body Se metabolism in mice.

In summary, results of these three studies unveil essential roles of SELENOH in embryogenesis, spermatogenesis, and glucose tolerance in mice. SELENOH plausibly plays upstream roles to optimize these physiological events in association with the transcriptional regulation of several selenoproteins and meiotic proteins. Future studies are warranted to understand the mechanisms by which SELENOH maintains such developmental and metabolic processes.

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