Neonatal estrogen and androgen disrupted sertoli cell proliferation, leading to inhibited testosterone synthesis in adulthood

Wang, Bensen

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https://hdl.handle.net/2142/121187 Copy

Description

Title

Neonatal estrogen and androgen disrupted sertoli cell proliferation, leading to inhibited testosterone synthesis in adulthood

Author(s)

Wang, Bensen

Issue Date

2023-05-16

Director of Research (if dissertation) or Advisor (if thesis)

Ko, CheMyong Jay

Department of Study

Comparative Biosciences

Discipline

VMS - Comparative Biosciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• Testosterone
• Sertoli cell
• Leydig cell
• Neonatal
• Testis

Abstract

In men, circulating testosterone influences health and fertility. In adult men, Leydig cells of the testis produce testosterone. Impaired Leydig cell proliferation, differentiation or function leads to hypoandrogenism (low circulating testosterone level) that causes muscle loss, low metabolic rate, and decreased sperm production and quality. In the developing testis, exposure to sex steroids is known to leave a lasting impact resulting in decreased testosterone synthesis in adulthood. In this study, I tested the hypothesis that a neonatal exposure to estrogen and androgen for an extended period alters the differentiation of Leydig cells, resulting in lower capacity of testosterone synthesis at adulthood. To test the hypothesis, pigs were used as an animal model because of their similarities in the anatomical and functional patterns of testis development, pathways for testosterone synthesis, and the regulatory mechanism of Leydig cell differentiation. In this study, neonatal piglet were treated with pellets that were designed to release estrogen (estradiol benzoate, EB) and androgen (trenbolone acetate, TBA) for the duration of 5 to 6 weeks. Microspheres were also used to deliver EB for a quicker but robust delivery for 1.5 to 2 weeks. Male pigs were treated one day after birth (postnatal day 1, PND1) with 3 different doses of androgen and estrogen: low dose (100mg TBA + 14 mg EB, delivered by pellet), high dose (200mg TBA + 28 mg EB, delivered by pellet), and high-extra (high dose + extra 5mg EB delivered by microsphere). Intact animals were used as negative controls and GnRH vaccine-injected animals were used as a positive control for inhibiting testosterone synthesis. H&E staining alone or with immunohistochemistry was used for assessing testosterone synthesis (CYP17, HSD17) in Leydig cells, identifying Sertoli cell (SOX9), and counting their cell numbers. The results showed that, at the age of 26 weeks, male pigs treated with the low dose did not exhibit a significant deviation from the intact control in their testis development and testosterone production, but the testes of the high dose and high+extra dose groups showed lower capacity of testosterone synthesis than intact control. Pigs treated with high+extra dose exhibited severe decrease in Sertoli cell number, indicating an earlier exposure to those sex steroids may give severe impact on Sertoli cell proliferation. Delayed expression of HSD17 in piglets proved that Leydig cell differentiation was inhibited by neonatal treatment of estrogen and androgen. Taken together, this study showed that extended neonatal exposure to androgen and estrogen inhibits Leydig cell differentiation and Sertoli cell proliferation in male pig, leaving lasting impact on testosterone production.

Graduation Semester

2023-08

Type of Resource

Thesis

Copyright and License Information

Copyright May 2023 Bensen Wang

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