PUBLICATION

Insulin-like 3 affects zebrafish spermatogenic cells directly and via Sertoli cells

Authors

Crespo, D., Assis, L.H.C., Zhang, Y.T., Safian, D., Furmanek, T., Skaftnesmo, K.O., Norberg, B., Ge, W., Choi, Y.C., den Broeder, M.J., Legler, J., Bogerd, J., Schulz, R.W.

ID

ZDB-PUB-210217-6

Date

2021

Source

Communications biology 4: 204 (Journal)

Registered Authors

Bogerd, Jan, den Broeder, Marjo, Ge, Wei, Schulz, Rüdiger W.

Keywords

none

Datasets

GEO:GSE152038, GEO:GSE116611

MeSH Terms

Zebrafish/genetics
Zebrafish/metabolism*
Animals
Signal Transduction
Tretinoin/metabolism
Proteins/genetics
Proteins/metabolism*
Gene Expression Regulation, Developmental
Spermatogonia/drug effects
Spermatogonia/metabolism*
Spermatogonia/pathology
HEK293 Cells
Apoptosis
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Male
Spermatogenesis*/drug effects
Insulin/genetics
Insulin/metabolism*
Humans
Sertoli Cells/drug effects
Sertoli Cells/metabolism*
Receptors, G-Protein-Coupled/genetics
Receptors, G-Protein-Coupled/metabolism
PPAR gamma/genetics
PPAR gamma/metabolism
Transcriptome

(all 27)

PubMed

33589679 Full text @ Commun Biol

Abstract

Pituitary hormones can use local signaling molecules to regulate target tissue functions. In adult zebrafish testes, follicle-stimulating hormone (Fsh) strongly increases the production of insulin-like 3 (Insl3), a Leydig cell-derived growth factor found in all vertebrates. Little information is available regarding Insl3 function in adult spermatogenesis. The Insl3 receptors Rxfp2a and 2b were expressed by type A spermatogonia and Sertoli and myoid cells, respectively, in zebrafish testis tissue. Loss of insl3 increased germ cell apoptosis in males starting at 9 months of age, but spermatogenesis appeared normal in fully fertile, younger adults. Insl3 changed the expression of 409 testicular genes. Among others, retinoic acid (RA) signaling was up- and peroxisome proliferator-activated receptor gamma (Pparg) signaling was down-regulated. Follow-up studies showed that RA and Pparg signaling mediated Insl3 effects, resulting in the increased production of differentiating spermatogonia. This suggests that Insl3 recruits two locally active nuclear receptor pathways to implement pituitary (Fsh) stimulation of spermatogenesis.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
aldh1a2	insl3^uua1/uua1	standard conditions	Adult	testis	RTPCR	Fig. 5
aldh1a2	WT	standard conditions	Adult	testis	RTPCR	Fig. 5
aldh1a2	WT	chemical treatment by injection: busulfan	Adult	testis	RNA-Seq	Fig. 5
aldh1a2	WT	standard conditions	Adult	testis	RNA-Seq	Fig. 5
amh	insl3^uua1/uua1	standard conditions	Adult	testis	RTPCR	Fig. 2
amh	WT	standard conditions	Adult	testis	RTPCR	Fig. 2
casp9	insl3^uua1/uua1	standard conditions	Adult	testis	RTPCR	Fig. 3
casp9	WT	standard conditions	Adult	testis	RTPCR	Fig. 3
cyp17a1	insl3^uua1/uua1	standard conditions	Adult	testis	RTPCR	Fig. 2
cyp17a1	WT	standard conditions	Adult	testis	RTPCR	Fig. 2

1 - 10 of 39

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by injection: busulfan	Adult	testis aldh1a2 expression increased amount, abnormal	Fig. 5
WT	chemical treatment by injection: busulfan	Adult	testis pparg expression increased amount, abnormal	Fig. 6
WT	chemical treatment by injection: busulfan	Adult	testis rxfp2a expression decreased amount, abnormal	Fig. 1
insl3^uua1/uua1	standard conditions	Adult	Sertoli cell apoptotic, abnormal	Fig. 3
insl3^uua1/uua1	standard conditions	Adult	spermatid apoptotic, abnormal	Fig. 3
insl3^uua1/uua1	standard conditions	Adult	spermatid decreased amount, abnormal	Fig. 2
insl3^uua1/uua1	standard conditions	Adult	spermatocyte apoptotic, abnormal	Fig. 3
insl3^uua1/uua1	standard conditions	Adult	spermatocyte decreased amount, abnormal	Fig. 2
insl3^uua1/uua1	standard conditions	Adult	spermatogonium apoptotic, abnormal	Fig. 3
insl3^uua1/uua1	standard conditions	Adult	spermatogonium apoptotic, abnormal	Fig. 2

1 - 10 of 19

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
sa1220		Point Mutation	pparg
sa1737		Point Mutation	pparg
uua1		Indel	insl3
uua3Tg	Tg(rxfp2a:EGFP)	Transgenic Insertion
uua4Tg	Tg(rxfp2b:mCherry)	Transgenic Insertion

1 - 5 of 5

Show

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
insl3	CRISPR1-insl3	CRISPR

Fish

Fish
insl3^uua1/uua1
pparg^{sa1220/sa1220}
pparg^{sa1737/sa1737}
uua3Tg
uua4Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
mCherry	EFG	mCherry

Mapping

Crespo et al., 2021 ZDB-PUB-210217-6 PMID:33589679

Insulin-like 3 affects zebrafish spermatogenic cells directly and via Sertoli cells

Crespo et al., 2021

ZDB-PUB-210217-6
PMID:33589679