Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without affecting meiosis I
Yong-Hyun Shin, … , Vasil Mico, Aleksandar Rajkovic
Yong-Hyun Shin, … , Vasil Mico, Aleksandar Rajkovic
Published May 15, 2017
Citation Information: J Clin Invest. 2017;127(6):2106-2117. https://doi.org/10.1172/JCI90281.
View: Text | PDF
Research Article Development Reproductive biology

Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without affecting meiosis I

Abstract

Following migration of primordial germ cells to the genital ridge, oogonia undergo several rounds of mitotic division and enter meiosis at approximately E13.5. Most oocytes arrest in the dictyate (diplotene) stage of meiosis circa E18.5. The genes necessary to drive oocyte differentiation in parallel with meiosis are unknown. Here, we have investigated whether expression of spermatogenesis and oogenesis bHLH transcription factor 1 (Sohlh1) and Sohlh2 coordinates oocyte differentiation within the embryonic ovary. We found that SOHLH2 protein was expressed in the mouse germline as early as E12.5 and preceded SOHLH1 protein expression, which occurred circa E15.5. SOHLH1 protein appearance at E15.5 correlated with SOHLH2 translocation from the cytoplasm into the nucleus and was dependent on SOHLH1 expression. NOBOX oogenesis homeobox (NOBOX) and LIM homeobox protein 8 (LHX8), two important regulators of postnatal oogenesis, were coexpressed with SOHLH1. Single deficiency of Sohlh1 or Sohlh2 disrupted the expression of LHX8 and NOBOX in the embryonic gonad without affecting meiosis. Sohlh1-KO infertility was rescued by conditional expression of the Sohlh1 transgene after the onset of meiosis. However, Sohlh1 or Sohlh2 transgene expression could not rescue Sohlh2-KO infertility due to a lack of Sohlh1 or Sohlh2 expression in rescued mice. Our results indicate that Sohlh1 and Sohlh2 are essential regulators of oocyte differentiation but do not affect meiosis I.

Authors

Yong-Hyun Shin, Yu Ren, Hitomi Suzuki, Kayla J. Golnoski, Hyo won Ahn, Vasil Mico, Aleksandar Rajkovic

×

Figure 6

Sohlh1 overexpression with Gdf9 promoter–driven Cre rescues Sohlh1–/– fertility but not the primordial follicle reserve.

Options: View larger image (or click on image) Download as PowerPoint
Sohlh1 overexpression with Gdf9 promoter–driven Cre rescues Sohlh1–/– f...
(A and B) Conditional expression of Sohlh1 from the CCS1 transgene with Gdf9-Cre rescued Sohlh1–/– folliculogenesis. Histology sections were stained with anti-NOBOX antibodies to identify oocyte nuclei. The WT ovary showed various stages of folliculogenesis, while the Sohlh1–/– ovary lacked oocytes at 5 weeks. CCS1 Sohlh1–/– mice showed normal folliculogenesis from primary to large antral follicles at 5 weeks and 8 months, but had an unusually low number of primordial follicles (n = 3 per group). (C) Primordial follicle numbers in WT and CCS1 Sohlh1–/– mice at 5 weeks and 8 months (n = 5 per group). (D and E) Fertility testing of CCS1 Sohlh1–/– mice over a period of 6 months (n = 3 per group). (F) Expression levels of Sohlh1, Sohlh2, mCherry, and Gdf9 in WT, Sohlh1-deficient (Sohlh1–/–), and Sohlh1–/–-rescued ovaries (CCS1 Sohlh1–/–). **P < 0.01 and ***P < 0.001, by 2-tailed Student’s t test. Data represent the mean ± SEM and are representative of at least 3 independent experiments.