Inefficient Sox9 upregulation and absence of Rspo1 repression lead to sex reversal in the B6.XYTIR mouse gonad

Author:

Cao Jiangqin1234,El Mansouri Fatima45,Reynoso Sofia3,Liu Zongping1,Zhu Jiaqiao126,Taketo Teruko3457

Affiliation:

1. College of Veterinary Medicine, Yangzhou University , Yangzhou, Jiangsu , China

2. Guangling College of Yangzhou University , Yangzhou, Jiangsu , China

3. Department of Biology, McGill University , Montreal, Quebec , Canada

4. Research Institute of McGill University Health Centre , Montreal, Quebec , Canada

5. Department of Surgery, McGill University , Montreal, Quebec , Canada

6. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses , Yangzhou, Jiangsu , China

7. Department of Obstetrics and Gynecology, McGill University , Montreal, Quebec , Canada

Abstract

Abstract Sry on the Y-chromosome upregulates Sox9, which in turn upregulates a set of genes such as Fgf9 to initiate testicular differentiation in the XY gonad. In the absence of Sry expression, genes such as Rspo1, Foxl2, and Runx1 support ovarian differentiation in the XX gonad. These two pathways antagonize each other to ensure the development of only one gonadal sex in normal development. In the B6.YTIR mouse, carrying the YTIR-chromosome on the B6 genetic background, Sry is expressed in a comparable manner with that in the B6.XY mouse, yet, only ovaries or ovotestes develop. We asked how testicular and ovarian differentiation pathways interact to determine the gonadal sex in the B6.YTIR mouse. Our results showed that (1) transcript levels of Sox9 were much lower than in B6.XY gonads while those of Rspo1 and Runx1 were as high as B6.XX gonads at 11.5 and 12.5 days postcoitum. (2) FOXL2-positive cells appeared in mosaic with SOX9-positive cells at 12.5 days postcoitum. (3) SOX9-positive cells formed testis cords in the central area while those disappeared to leave only FOXL2-positive cells in the poles or the entire area at 13.5 days postcoitum. (4) No difference was found at transcript levels of all genes between the left and right gonads up to 12.5 days postcoitum, although ovotestes developed much more frequently on the left than the right at 13.5 days postcoitum. These results suggest that inefficient Sox9 upregulation and the absence of Rspo1 repression prevent testicular differentiation in the B6.YTIR gonad.

Funder

CIHR

NSERC

Yangzhou University International Academic Exchange Fund

Jiangsu Province Postgraduate Practice Innovation Program

Natural Science Foundation of Jiangsu Province

Publisher

Oxford University Press (OUP)

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