A granulosa cell or follicular cell is a

somatic cell A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells com ...

of the

sex cord In embryogenesis, the sex cords (primitive sex cords, primitive seminiferous cords, or gonadal cords) are structures that develop from the genital ridges that further differentiate based on an embryo's sex. After sexual differentiation, at day 49, ...

that is closely associated with the developing female

gamete A gamete (; , ultimately ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. In species that produce ...

(called an

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...

or egg) in the

ovary The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...

Structure and function

In the

primordial Primordial may refer to: * Primordial era, an era after the Big Bang. See Chronology of the universe * Primordial sea (a.k.a. primordial ocean, ooze or soup). See Abiogenesis * Primordial nuclide, nuclides, a few radioactive, that formed before t ...

ovarian follicle An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with ...

, and later in follicle development (

folliculogenesis :''Although the process is similar in many animals, this article will deal exclusively with human folliculogenesis.'' In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains a ...

), granulosa cells advance to form a multilayered

cumulus oophorus The cumulus oophorus, (discus proligerus), is a cluster of cells that surround the oocyte both in the ovarian follicle and after ovulation. In the antral follicle, it may be regarded as an extension of the membrana granulosa. The innermost layer ...

surrounding the

in the preovulatory or

antral ''This is a disambiguation page for the biological term. For the 2018 horror movie, see Antrum (film)'' In biology, antrum is a general term for a cavity or chamber, which may have specific meaning in reference to certain organs or sites in the bo ...

(or Graafian) follicle. The major functions of granulosa cells include the production of

sex steroid Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...

s, as well as myriad growth factors thought to interact with the

during its development. The sex steroid production begins with

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, ...

(FSH) from the anterior pituitary, stimulating granulosa cells to convert

androgens An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...

(coming from the

thecal cell The theca folliculi comprise a layer of the ovarian follicles. They appear as the follicles become secondary follicles. The theca are divided into two layers, the theca interna and the theca externa. Theca cells are a group of endocrine cel ...

s) to

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...

during the

follicular phase The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the estrous cycle (or, in primates for example, the menstrual cycle) during which follicles in the ovary mature from primary follicle to a fully ...

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 ...

. However, after ovulation the granulosa cells turn into granulosa lutein cells that produce

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 majo ...

. The progesterone may maintain a potential pregnancy and causes production of a thick cervical mucus that inhibits sperm entry into the uterus.

Embryology of ovarian granulosa cells

In the

development of the urinary and reproductive organs The development of the urinary system begins during prenatal development, and relates to the development of the urogenital system – both the organs of the urinary system and the sex organs of the reproductive system. The development continues a ...

, the

oogonia An oogonium (plural oogonia) is a small diploid cell which, upon maturation, forms a primordial follicle in a female fetus or the female (haploid or diploid) gametangium of certain thallophytes. In the mammalian fetus Oogonia are formed in l ...

become invaginated in the

gonadal ridge The genital ridge (or gonadal ridge) is the precursor to the gonads. The genital ridge initially consists mainly of mesenchyme and cells of underlying mesonephric origin. Once oogonia enter this area they attempt to associate with these somatic ce ...

. The embryological origin of granulosa cells remains controversial. In the 1970s, evidence emerged that the first cells to make contact with the oogonia were of mesonephric origin. It was suggested that mesonephric cells already closely associated with the oogonia proliferated throughout development to form the granulosa cell layer. Recently, this hypothesis has been challenged with some thorough

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures v ...

. Sawyer et al. hypothesized that in sheep most of the granulosa cells develop from cells of the

mesothelium The mesothelium is a membrane composed of simple squamous epithelial cells of mesodermal origin, which forms the lining of several body cavities: the pleura ( pleural cavity around the lungs), peritoneum ( abdominopelvic cavity including the mes ...

(i.e., epithelial cells from the presumptive surface epithelium of the ovary). In 2013, it was proposed that both granulosa cells and the ovarian surface epithelial cells are instead derived from a precursor cell called gonadal-ridge epithelial-like cell.

Granulosa Cell Types

''Cumulus Cells (CC) vs Mural Granulosa Cells (MGC)'' Cumulus cells surround the oocyte. They provide nutrients to the oocyte and influence the development of the oocyte in a paracrine fashion. Mural granulosa cells line the follicular wall and surround the fluid-filled antrum. The oocyte secretes factors that determine the functional differences between CCs and MGGs. CCs primarily support growth and development of the oocyte whereas MGCs primarily serve an endocrine function and support the growth of the follicle. Cumulus cells aid in oocyte development and show higher expression of SLC38A3, a transporter for amino acids, and Aldoa, Eno1, Ldh1, Pfkp, Pkm2, and Tpi1, enzymes responsible for glycolysis. MGCs are more steroidogenically active and have higher levels of mRNA expression of steroidogenic enzymes such as cytochrome P450. MGCs produce an increasing amount of estrogen which leads to the LH surge. Following the LH surge, cumulus cells undergo cumulus expansion, in which they proliferate at a ten-fold higher rate than MGCs in response to FSH. During expansion CCs also produce a mucified matrix required for ovulation.

Cell culture

Cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This tec ...

of granulosa cells can be performed ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

''. Plating density (number of cells per volume of culture medium) plays a critical role for the differentiation. A lower plating density makes granulosa cells exhibit estrogen production, while a higher plating density makes them appear as

producing

theca lutein cell The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is th ...

Additional images

References

External links

* - "Female Reproductive System: ovary, cumulus oophorus" * - "Female Reproductive System: ovary, membrana granulosa" * {{MeshName, Granulosa+Cells Steroid hormone secreting cells Human female endocrine system