YAP1 and WWTR1 are required for murine pregnancy initiation

Area of Science:

• Reproductive Biology
• Cell Signaling
• Developmental Biology

Background:

• Endometrial decidualization is crucial for successful pregnancy.
• The Hippo signaling pathway's role in decidualization is not fully understood.
• YAP1 and WWTR1 are known Hippo pathway effectors implicated in human decidualization in vitro.

Purpose of the Study:

• To investigate the in vivo function of YAP1 and WWTR1 in murine decidualization and pregnancy initiation.
• To determine the consequences of Yap1 and Wwtr1 mutations on endometrial receptivity and embryonic development.

Main Methods:

• Generation of progesterone receptor Cre-mediated triple allele mutants for Yap1 and Wwtr1.
• Analysis of decidualization, endometrial receptivity, and embryonic development at 7.5 days post-coitus.
• Bulk mRNA sequencing to assess transcriptional profiles and maternal remodeling.

Main Results:

• Yap1 and Wwtr1 triple mutants displayed subfertility, impaired decidualization, and reduced endometrial receptivity.
• Mutant dams showed delayed embryonic development and altered maternal remodeling, with changes in extracellular matrix genes.
• Transcriptional profiles were enriched for terms associated with pregnancy complications like pre-eclampsia and endometriosis.

Conclusions:

• YAP1 and WWTR1 are essential for successful mammalian pregnancy initiation.
• Disruption of the Hippo pathway affects endometrial receptivity and maternal-fetal interactions.
• These findings link YAP1/WWTR1 to fertility and pregnancy disorders.