Hormonal regulation occurs at every stage of

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...

. A milieu of hormones simultaneously affects development of the

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...

during

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

and the mother, including

human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...

(hCG) and

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

(P4).

Embryogenesis

Human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...

(hCG),

, 17β-estradiol, endorphins and

gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...

(GnRH) synthesis are rapidly upregulated by the developing embryo following fertilization of the ovum. During early embryonic development,

paracrine Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse ove ...

juxtacrine In biology, juxtacrine signalling (or contact-dependent signalling) is a type of cell–cell or cell–extracellular matrix signalling in multicellular organisms that requires close contact. In this type of signalling, a ligand on one surface bi ...

signaling of hCG induces

blastulation Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula (fro ...

and

neurulation Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube. The embryo at this stage is termed the neurula. The process begins when the notochord induces the formati ...

. 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 Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...

hESC to neural precursor cells.Gallego, M. et al (2009). Opioid and progesterone signaling is obligatory for early human embryogenesis. Stem Cells Development, 18, 737–740.Gallego, M. et al (2010). The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes. Stem Cell Research & Therapy, 1, 1-13 Suppression of P4 signaling following withdrawal of progesterone, or treatment with the progesterone receptor antagonist RU-486 (

mifepristone Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of p ...

), inhibits the differentiation of hESC colonies into embryoid bodies (

) or rosettes (

). 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.

Influence of maternal hormones

Pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

-associated

hormones A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...

such as hCG and sex steroids regulate numerous biological processes in the maternal system prior to and during pregnancy. The embryo orchestrates biological changes that occur in both the embryo and the mother. The embryo upregulates hCG, drives growth of the cell, and upregulates P4 production driving development. hCG and P4 direct changes in the mother to enable successful pregnancy (see below) via upregulation of specific hormones that act to direct both endocrinological and biological changes within the mother for successful pregnancy.

Maintenance of the endometrial lining

The early embryo has 1–2 weeks in order to produce sufficient hCG in order to stabilize the endometrial lining to allow for blastocyst attachment. The dramatic increase in trophoblastic and corpus luteal hCG synthesis signals both blastocyst and corpus luteal production of P4, crucial for the maintenance of the

endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...

Attachment and invasion of cytotrophoblast into endometrium

hCG secreted by cytotrophoblastic cells of the blastocyst controls endometrial tissue remodeling by both activation of matrix matalloproteinases (MMP) that control the maternal extracellular matrix and inhibition of tissue-inhibitors of matrix-metalloproteinases (TIMP). hCG mediates invasion and attachment to the endometrium. Low levels of hCG increase risk of

pre-eclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...

Uterine angiogenesis

Uterine

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

is upregulated by human chorionic gonadotropin and progesterone and downregulated by estrogen. The balance of influences of progesterone and estrogen determine the state of angiogenesis in the uterus during early pregnancy.

Suppression of the maternal immune system

High levels of progesterone produced by the embryonic

placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...

regulate

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

proliferation at the maternal-fetal interface, locally suppressing maternal

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

against the developing embryo.

Suppression of GnRH secretion to prevent further follicular maturation

Negative feedback of progesterone inhibits hypothalamic pulsatile GnRH neurosecretion, ovulatory GnRH release and pituitary gonadotropin surges thereby effectively preventing further follicular maturation.

Preparation of maternal metabolic systems

Progesterone regulates metabolism of

carbohydrates In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or may ...

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

, and

lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

, resulting in physiological changes associated with pregnancy. The mix of hormones characteristic of early pregnancy promote natural growth of maternal tissues and weight gain. In the second half of pregnancy, progesterone and prolactin prepare the mammary glands for lactation.Atwood, C. et al (2000). Progesterone induces side-branching of the ductal epithelium in the

mammary glands A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in prima ...

of peripubertal mice. Journal of Endocrinology, 167, 39-52.

Preparation of mammary glands for lactation

Estrogens and progesterone promote mammary epithelial cell proliferation resulting in the formation of the primary and secondary ductal structure. Progesterone induces formation of tertiary side-branches in the mammary glands during puberty and during the luteal phase of the

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...

upon which lobuloalveolar structures form under the influence of

prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...

. Prolactin stimulates

lactogenesis A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in primat ...

Induction of sleep

hCG appears to be

soporific Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

during pregnancy; levels of hCG correlate with sleep changes during pregnancy, and administration of hCG increases sleep in rats likely via neuronal LHCGR.Rao, C. et al (1995). Peripheral and intracerebroventricular administration of human chorionic gonadotropin alters several hippocampus-associated behaviors in cycling female rats. Hormones and Behavior, 29, 42-58

References

{{Human reproductive physiology Endocrinology Human reproduction