The transcriptional regulatory network modulating human trophoblast stem cells to extravillous trophoblast differentiation.

During human pregnancy, extravillous trophoblasts play crucial roles in placental invasion into the maternal decidua and spiral artery remodeling. However, regulatory factors and their action mechanisms modulating human extravillous trophoblast specification have been unknown. By analyzing dynamic changes in transcriptome and enhancer profile during human trophoblast stem cell to extravillous trophoblast differentiation, we define stage-specific regulators, including an early-stage transcription factor, TFAP2C, and multiple late-stage transcription factors. Loss-of-function studies confirm the requirement of all transcription factors identified for adequate differentiation, and we reveal that the dynamic changes in the levels of TFAP2C are essential. Notably, TFAP2C pre-occupies the regulatory elements of the inactive extravillous trophoblast-active genes during the early stage of differentiation, and the late-stage transcription factors directly activate extravillous trophoblast-active genes, including themselves as differentiation further progresses, suggesting sequential actions of transcription factors assuring differentiation. Our results reveal stage-specific transcription factors and their inter-connected regulatory mechanisms modulating extravillous trophoblast differentiation, providing a framework for understanding early human placentation and placenta-related complications.

Now is the time to safeguard access to emergency contraception as abortion restrictions sweep the United States.

Abortion and contraception are essential components of reproductive healthcare. As 26 states are likely to severely restrict access to abortion following the Supreme Court decision in Dobbs v. Jackson Women's Health Organization, access to emergency contraception will be more important than ever. Existing barriers to emergency contraception - including cost, obstacles to over-the-counter purchase, low awareness and availability of the most effective options, myths about safety and mechanism of action - already substantially limit access. Proactive solutions include public information campaigns; healthcare provider education about all emergency contraceptive options, including IUDs and advance provision of emergency contraceptive pills; innovative service delivery options such as vending machines and community distribution programs; and policy initiatives to ensure insurance coverage, eliminate pharmacy refusals, and support all service delivery options. In addition, we urge the U.S. Food and Drug Administration to approve updated labeling to align with the best available evidence that oral contraceptive pills work before ovulation and do not prevent implantation of a fertilized egg, as this language contributes to public confusion and access barriers. In the face of extreme limits on reproductive healthcare, now is the time to expand and protect access to emergency contraception so that everyone has the possibility of preventing pregnancy after unprotected sex or sexual assault.