Endocrinology of reproduction

Hormonal regulation occurs at every stage of development. A milieu of hormones simultaneously affects development of the fetus during embryogenesis and the mother, including human chorionic gonadotropin (hCG) and progesterone (P4).

Human chorionic gonadotropin (hCG), progesterone, 17β-estradiol, endorphins and gonadotropin-releasing hormone (GnRH) synthesis are rapidly upregulated by the developing embryo following fertilization of the ovum.

During early embryonic development, paracrine/juxtacrine signaling of hCG induces blastulation and neurulation. An in vitro model of early human embryogenesis (human embryonic stem cells (hESCs)) has demonstrated that hCG promotes cell proliferation via the LH/hCG receptor (LHCGR). hCG signaling upregulates the expression of steroidogenic acute regulatory protein (StAR)-mediated cholesterol transport and the synthesis of progesterone in hESC. The production of progesterone at this time induces embryroid body (akin to blastulation) and rosette (akin to neurulation) formation in vitro. Progesterone induces the differentiation of pluripotent hESC to neural precursor cells.

Suppression of P4 signaling following withdrawal of progesterone, or treatment with the progesterone receptor antagonist RU-486 (mifepristone), inhibits the differentiation of hESC colonies into embryoid bodies (blastulation) or rosettes (neurulation). RU-486, a drug commonly used to terminate pregnancy in its early stages, acts not only to abort the embryo, but also to inhibit normal embryonic development.

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