A granulosa cell or follicular cell is a
somatic cell of the
sex cord 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 femal ...
or egg) in the
ovary of
mammals.
Structure and function
In the
primordial 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 t ...
, 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
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 femal ...
in the preovulatory or
antral (or Graafian) follicle.
The major functions of granulosa cells include the production of
sex steroids, as well as myriad growth factors thought to interact with the
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 femal ...
during its development. The sex steroid production begins with
follicle-stimulating hormone (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 cells ...
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 ...
by
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 ful ...
of the
menstrual cycle. However, after ovulation the granulosa cells turn into
granulosa 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 ...
s that produce
progesterone. 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 lar ...
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 vi ...
. Sawyer et al. hypothesized that in sheep most of the granulosa cells develop from cells of the
mesothelium (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
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
. 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 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 ...
''.
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
progesterone producing
theca lutein cells.
Additional images
See also
*
Granulosa cell tumour
*
Ovulation
Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...
*
Membrana granulosa
The larger ovarian follicles
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 ...
*
List of human cell types derived from the germ layers
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