Suppression of Sertoli cell tumour development during the first wave of spermatogenesis in inhibin α-deficient mice

Jenna T. Haverfield, Peter G. Stanton, Kate L. Loveland, Heba Zahid, Peter K. Nicholls, Justine S. Olcorn, Yogeshwar Makanji, Catherine M. Itman, Evan R. Simpson, Sarah J. Meachem

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A dynamic partnership between follicle-stimulating hormone (FSH) and activin is required for normal Sertoli cell development and fertility. Disruptions to this partnership trigger Sertoli cells to deviate from their normal developmental pathway, as observed in inhibin α-knockout (Inha-KO) mice, which feature Sertoli cell tumours in adulthood. Here, we identified the developmental windows by which adult Sertoli cell tumourigenesis is most FSH sensitive. FSH was suppressed for 7 days in Inha-KO mice and wild-type littermates during the 1st, 2nd or 4th week after birth and culled in the 5th week to assess the effect on adult Sertoli cell development. Tumour growth was profoundly reduced in adult Inha-KO mice in response to FSH suppression during Weeks 1 and 2, but not Week 4. Proliferative Sertoli cells were markedly reduced in adult Inha-KO mice following FSH suppression during Weeks 1, 2 or 4, resulting in levels similar to those in wild-type mice, with greatest effect observed at the 2 week time point. Apoptotic Sertoli cells increased in adult Inha-KO mice after FSH suppression during Week 4. In conclusion, acute FSH suppression during the 1st or 2nd week after birth in Inha-KO mice profoundly suppresses Sertoli cell tumour progression, probably by inhibiting proliferation in the adult, with early postnatal Sertoli cells being most sensitive to FSH action.

Original languageEnglish
Pages (from-to)609-620
Number of pages12
JournalReproduction, Fertility and Development
Volume29
Issue number3
DOIs
Publication statusPublished - 2017

Keywords

  • cancer
  • FSH
  • testis

Cite this

@article{450c51f4319045ffbfbab78dc9b06802,
title = "Suppression of Sertoli cell tumour development during the first wave of spermatogenesis in inhibin α-deficient mice",
abstract = "A dynamic partnership between follicle-stimulating hormone (FSH) and activin is required for normal Sertoli cell development and fertility. Disruptions to this partnership trigger Sertoli cells to deviate from their normal developmental pathway, as observed in inhibin α-knockout (Inha-KO) mice, which feature Sertoli cell tumours in adulthood. Here, we identified the developmental windows by which adult Sertoli cell tumourigenesis is most FSH sensitive. FSH was suppressed for 7 days in Inha-KO mice and wild-type littermates during the 1st, 2nd or 4th week after birth and culled in the 5th week to assess the effect on adult Sertoli cell development. Tumour growth was profoundly reduced in adult Inha-KO mice in response to FSH suppression during Weeks 1 and 2, but not Week 4. Proliferative Sertoli cells were markedly reduced in adult Inha-KO mice following FSH suppression during Weeks 1, 2 or 4, resulting in levels similar to those in wild-type mice, with greatest effect observed at the 2 week time point. Apoptotic Sertoli cells increased in adult Inha-KO mice after FSH suppression during Week 4. In conclusion, acute FSH suppression during the 1st or 2nd week after birth in Inha-KO mice profoundly suppresses Sertoli cell tumour progression, probably by inhibiting proliferation in the adult, with early postnatal Sertoli cells being most sensitive to FSH action.",
keywords = "cancer, FSH, testis",
author = "Haverfield, {Jenna T.} and Stanton, {Peter G.} and Loveland, {Kate L.} and Heba Zahid and Nicholls, {Peter K.} and Olcorn, {Justine S.} and Yogeshwar Makanji and Itman, {Catherine M.} and Simpson, {Evan R.} and Meachem, {Sarah J.}",
year = "2017",
doi = "10.1071/RD15239",
language = "English",
volume = "29",
pages = "609--620",
journal = "Reproduction, Fertility and Development",
issn = "1031-3613",
publisher = "CSIRO",
number = "3",

}

Suppression of Sertoli cell tumour development during the first wave of spermatogenesis in inhibin α-deficient mice. / Haverfield, Jenna T.; Stanton, Peter G.; Loveland, Kate L.; Zahid, Heba; Nicholls, Peter K.; Olcorn, Justine S.; Makanji, Yogeshwar; Itman, Catherine M.; Simpson, Evan R.; Meachem, Sarah J.

In: Reproduction, Fertility and Development, Vol. 29, No. 3, 2017, p. 609-620.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Suppression of Sertoli cell tumour development during the first wave of spermatogenesis in inhibin α-deficient mice

AU - Haverfield, Jenna T.

AU - Stanton, Peter G.

AU - Loveland, Kate L.

AU - Zahid, Heba

AU - Nicholls, Peter K.

AU - Olcorn, Justine S.

AU - Makanji, Yogeshwar

AU - Itman, Catherine M.

AU - Simpson, Evan R.

AU - Meachem, Sarah J.

PY - 2017

Y1 - 2017

N2 - A dynamic partnership between follicle-stimulating hormone (FSH) and activin is required for normal Sertoli cell development and fertility. Disruptions to this partnership trigger Sertoli cells to deviate from their normal developmental pathway, as observed in inhibin α-knockout (Inha-KO) mice, which feature Sertoli cell tumours in adulthood. Here, we identified the developmental windows by which adult Sertoli cell tumourigenesis is most FSH sensitive. FSH was suppressed for 7 days in Inha-KO mice and wild-type littermates during the 1st, 2nd or 4th week after birth and culled in the 5th week to assess the effect on adult Sertoli cell development. Tumour growth was profoundly reduced in adult Inha-KO mice in response to FSH suppression during Weeks 1 and 2, but not Week 4. Proliferative Sertoli cells were markedly reduced in adult Inha-KO mice following FSH suppression during Weeks 1, 2 or 4, resulting in levels similar to those in wild-type mice, with greatest effect observed at the 2 week time point. Apoptotic Sertoli cells increased in adult Inha-KO mice after FSH suppression during Week 4. In conclusion, acute FSH suppression during the 1st or 2nd week after birth in Inha-KO mice profoundly suppresses Sertoli cell tumour progression, probably by inhibiting proliferation in the adult, with early postnatal Sertoli cells being most sensitive to FSH action.

AB - A dynamic partnership between follicle-stimulating hormone (FSH) and activin is required for normal Sertoli cell development and fertility. Disruptions to this partnership trigger Sertoli cells to deviate from their normal developmental pathway, as observed in inhibin α-knockout (Inha-KO) mice, which feature Sertoli cell tumours in adulthood. Here, we identified the developmental windows by which adult Sertoli cell tumourigenesis is most FSH sensitive. FSH was suppressed for 7 days in Inha-KO mice and wild-type littermates during the 1st, 2nd or 4th week after birth and culled in the 5th week to assess the effect on adult Sertoli cell development. Tumour growth was profoundly reduced in adult Inha-KO mice in response to FSH suppression during Weeks 1 and 2, but not Week 4. Proliferative Sertoli cells were markedly reduced in adult Inha-KO mice following FSH suppression during Weeks 1, 2 or 4, resulting in levels similar to those in wild-type mice, with greatest effect observed at the 2 week time point. Apoptotic Sertoli cells increased in adult Inha-KO mice after FSH suppression during Week 4. In conclusion, acute FSH suppression during the 1st or 2nd week after birth in Inha-KO mice profoundly suppresses Sertoli cell tumour progression, probably by inhibiting proliferation in the adult, with early postnatal Sertoli cells being most sensitive to FSH action.

KW - cancer

KW - FSH

KW - testis

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U2 - 10.1071/RD15239

DO - 10.1071/RD15239

M3 - Article

VL - 29

SP - 609

EP - 620

JO - Reproduction, Fertility and Development

JF - Reproduction, Fertility and Development

SN - 1031-3613

IS - 3

ER -