Embryonic diapause

Last updated

Embryonic diapause [lower-alpha 1] (delayed implantation in mammals) is a reproductive strategy used by a number of animal species across different biological classes. In more than 130 types of mammals where this takes place, the process occurs at the blastocyst stage of embryonic development, [1] and is characterized by a dramatic reduction or complete cessation of mitotic activity, arresting most often in the G0 or G1 phase of division. [2]

Contents

In placental embryonic diapause, the blastocyst does not immediately implant in the uterus after sexual reproduction has resulted in the zygote, but rather remains in this non-dividing state of dormancy until conditions allow for attachment to the uterine wall to proceed as normal. [3] As a result, the normal gestation period is extended for a species-specific time. [4] [5]

Diapause provides a survival advantage to offspring, because birth or emergence of young can be timed to coincide with the most hospitable conditions, regardless of when mating occurs or length of gestation; any such gain in survival rates of progeny confers an evolutionary advantage.

Evolutionary significance

Organisms which undergo embryonic diapause are able to synchronize the birth of offspring to the most favorable conditions for reproductive success, irrespective of when mating took place. [3] Many different factors can induce embryonic diapause, such as the time of year, temperature, lactation and supply of food. [3]

Embryonic diapause is a relatively widespread phenomenon outside of mammals, with known occurrence in the reproductive cycles of many insects, nematodes, fish, and other non-mammalian vertebrates. [6] It has been observed in approximately 130 mammalian species, [7] which is less than two percent of all species of mammals. [8] These include certain rodents, bears, armadillos, mustelids (e.g. weasels and badgers), and marsupials (e.g. kangaroos). Some groups only have one species that undergoes embryonic diapause, such as the roe deer in the order Artiodactyla. [5]

Experimental induction of embryonic discontinuous development within species which do not spontaneously undergo embryonic diapause in nature has been achieved; reversible developmental arrest was successfully demonstrated. This may be evidence for the evolutionary significance of this phenomenon, with latent capacity for diapause potentially present in a much wider segment of species than known to occur naturally. [8] [9]

General mechanism

All multicellular organisms, from their conception, begin as a small number of cells and only grow and develop as those cells divide. In organisms which are capable of embryonic diapause, in non-ideal reproductive conditions, there is a cessation of cellular division which prevents the embryo from growing and maturing, delaying the maturation of the embryo until conditions are ideal enough to promote the survival of the offspring, and in some cases, the mother.

Regulation of the cell cycle as it relates to embryonic diapause has been linked to the dacapo gene in the fruit fly, responsible for inhibiting the formation of cyclin E-cdk2 complexes necessary for DNA synthesis. There is also evidence pointing to the upregulation of B cell translocation gene 1 (Btg1) in the mouse embryo during diapause, another known regulator of the cell cycle, responsible for inhibiting transition from G0/G1. Other studies have demonstrated, inversely, the lack of involvement of more common regulators of the cell cycle such as p53 within the placental model of embryonic diapause. [2] While much of the molecular regulation involved in activating dormant blastocysts has been characterized, little widely applicable characterization is available regarding entry into diapause, and the conditions which enable a blastocyst to remain dormant. Once the embryo exits diapause arrest and resumes regular development, no adverse effects are observed. [10]

Specifically within placental embryonic diapause, this cessation is led by the intentional failure of the blastocyst to implant in the uterine wall, which is an essential component in developmental progression in these species. [11] Hormones relating to the failed implantation also contribute to the embryonic arrest. [9]

Types

There are two distinct forms of embryonic diapause, characterized by different conditions of onset. Facultative diapause occurs in response to certain environmental or metabolic stressors, such as drastic changes in temperature, feeding, or lactation. [10] Obligate diapause occurs regularly in the reproductive cycle of the affected species, and is often associated with seasonal changes and photo-period. [10]

Facultative diapause

Mechanism of facultative embryonic diapause Fac dia.png
Mechanism of facultative embryonic diapause

Facultative diapause is regulated by several factors, including the maternal environment and ovarian competency, the pituitary gland, and metabolic stress and lactation. [2]

With regards to the many other regulators of this form of diapause, in placental mammals, facultative diapause is most often the result of fertilization shortly following the birth of a previous litter, The consequential pups suckling during lactation promotes prolactin to be released. This in turn reduces progesterone secretion from the corpus luteum in a pregnant female. The corpus luteum is a temporary endocrine organ that is formed from the leftover cells from the ovarian follicle in the ovary, once it has released a mature ovum. The main function of the corpus luteum is to secrete progesterone during pregnancy in order to maintain the uterine environment needed. Prolactin acting on the corpus luteum causes the progesterone level to be below optimal concentration and therefore induces embryonic facultative diapause.

Each species that undergoes facultative diapause tends to have a specific developmental stage, that is genetically determined, in which this process is initiated. This form of diapause is most well studied in rodents and marsupials [2] but has been identified in many other species, including non-mammals. It is not clear how well the mechanisms studied for the onset, maintenance and release from facultative diapause in the rodent model apply to these other species.

Obligate diapause

Obligate (adj: by necessity) diapause (a.k.a. seasonal delayed implantation) is a mechanism ensuring the birth of offspring is timed during optimal environmental conditions, to ensure maximal survival. [12] [9] The proposed mechanism is to separate conception and parturition (birth) so that each can occur at the most favourable time of year. [9]

Obligate diapause is activated and deactivated by changes to the number of daylight hours within a day (photoperiod) and hence, occurs within specific seasons. [10] While obligate diapause occurs in a variety of species in different groups, there are significant variations in diapause length. Western spotted skunks (Spilogale gracilis) have a diapause of around 200 days while American minks (Neogale vison) only have a diapause of around fourteen days. [10]

Similarly to facultative diapause, a series of hormonal changes arrest the blastocyst development, prior to implantation, preventing continued growth of the embryo. However, in obligate diapause, the blastocyst shall enter into the dormant state in every reproductive season. This means every blastocyst a mother produces shall enter a period of diapause. [10]

Close regulation of obligate diapause is essential for survival of the mother and offspring. Premature diapause can result in forgone growth and breeding opportunities and late diapause can result in death due to adverse conditions. [13]

Prior to the vernal equinox, [lower-alpha 2] the photoperiod is less than 12 hours. This increases the production of melatonin in the pineal gland. Due to the inhibitory relationship between melatonin and prolactin, this increase in melatonin decreases prolactin secretion from the pituitary gland. The decrease in prolactin consequently decreases progesterone production in the corpus luteum, preventing development of the blastocyst. This induces embryonic diapause. [10]

After the vernal equinox, the photoperiod is greater than 12 hours. This decreases the production of melatonin in the pineal gland and, therefore, increases the prolactin and progesterone production in the pituitary gland and corpus luteum respectively. [10]

The increase in prolactin induces expression of the gene Odc (ornithine decarboxylase). The Odc gene produces the ODC protein, a rate-limiting enzyme in the production of the polyamine, putrescine, within the uterine environment. The presence of putrescine may indicate a role in inducing the escape of the embryo from obligate diapause. [10]

Embryonic stem cells

Embryonic stem cells (ESCs) have the potential to allow for further understanding of the mechanisms controlling embryonic diapause. [13] This is because the ESCs and diapausing blastocysts having very similar transcriptome profiles. [13] ESCs are derived from the undifferentiated inner mass cells of blastocysts of an embryo – with the capability of continual proliferation in vitro. [13] ESCs are mostly derived from mouse models, at the point where the ESCs are at optimal efficiency and are able to enter diapause. [3]

Both diapausing blastocysts and ESCs have transcriptome profile similarities, including downregulation of metabolism, biosynthesis and gene expression pathways. [3] These similarities allow for the potential to use ESCs as a cellular model to identify the molecular factors which regulate embryonic diapause. [13]

See also

Notes

  1. Diapause, from late 19th century English: dia- 'through' + pause- 'delay'.[ citation needed ]
  2. The vernal equinox is the March equinox in the northern hemisphere, and the September equinox in the southern hemisphere.

Related Research Articles

<span class="mw-page-title-main">Endometrium</span> Inner mucous membrane of the mammalian uterus

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 layer thickens and then is shed during menstruation in humans and some other mammals, including other apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus. The speculated presence of an endometrial microbiota has been argued against.

<span class="mw-page-title-main">Pregnancy (mammals)</span> Period of reproduction

In mammals, pregnancy is the period of reproduction during which a female carries one or more live offspring from implantation in the uterus through gestation. It begins when a fertilized zygote implants in the female's uterus, and ends once it leaves the uterus.

<span class="mw-page-title-main">Uterus</span> Female sex organ in mammals

The uterus or womb is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more embryos until birth. The uterus is a hormone-responsive sex organ that contains glands in its lining that secrete uterine milk for embryonic nourishment.

<span class="mw-page-title-main">Placenta</span> Organ that connects the fetus to the uterine wall

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 maternal and fetal circulations, and is an important endocrine organ, producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth. Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.

<span class="mw-page-title-main">Menstrual cycle</span> Natural changes in the human female reproductive system

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 makes pregnancy possible. The ovarian cycle controls the production and release of eggs and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive an embryo. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a median length of 28 days, and continue for about 30–45 years.

Mammalian embryogenesis is the process of cell division and cellular differentiation during early prenatal development which leads to the development of a mammalian embryo.

<span class="mw-page-title-main">Blastocyst</span> Structure formed around day 5 of mammalian embryonic development

The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently forms the embryo, and an outer layer of trophoblast cells called the trophectoderm. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. In the late blastocyst, the trophectoderm is known as the trophoblast. The trophoblast gives rise to the chorion and amnion, the two fetal membranes that surround the embryo. The placenta derives from the embryonic chorion and the underlying uterine tissue of the mother.

<span class="mw-page-title-main">Corpus luteum</span> Temporary endocrine structure in ovaries

The corpus luteum 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 the remains of the ovarian follicle that has released a mature ovum during a previous ovulation.

<span class="mw-page-title-main">Trophoblast</span> Early embryonic structure that gives rise to the placenta

The trophoblast is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the placenta. They form during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg to become extraembryonic structures that do not directly contribute to the embryo. After blastulation, the trophoblast is contiguous with the ectoderm of the embryo and is referred to as the trophectoderm. After the first differentiation, the cells in the human embryo lose their totipotency because they can no longer form a trophoblast. They become pluripotent stem cells.

In mammalian species, pseudopregnancy is a physical state whereby all the signs and symptoms of pregnancy are exhibited, with the exception of the presence of a fetus, creating a false pregnancy. The corpus luteum is responsible for the development of maternal behavior and lactation, which are mediated by the continued production of progesterone by the corpus luteum through some or all of pregnancy. In most species, the corpus luteum is degraded in the absence of a pregnancy. However, in some species, the corpus luteum may persist in the absence of pregnancy and cause "pseudopregnancy", in which the female will exhibit clinical signs of pregnancy.

Luteolysis is the structural and functional degradation of the corpus luteum, which occurs at the end of the luteal phase of both the estrous and menstrual cycles in the absence of pregnancy.

<span class="mw-page-title-main">Luteal phase</span> The latter part of the menstrual cycle associated with ovulation and an increase in progesterone

The menstrual cycle is on average 28 days in length. It begins with menses during the follicular phase, followed by ovulation and ending with the luteal phase. Unlike the follicular phase which can vary in length among individuals, the luteal phase is typically fixed at approximately 14 days and is characterized by changes to hormone levels, such as an increase in progesterone and estrogen levels, decrease in gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), changes to the endometrial lining to promote implantation of the fertilized egg, and development of the corpus luteum. In the absence of fertilization by sperm, the corpus luteum degenerates leading to a decrease in progesterone and estrogen, an increase in FSH and LH, and shedding of the endometrial lining (menses) to begin the menstrual cycle again.

<span class="mw-page-title-main">Syncytiotrophoblast</span> Embryonic cell of the placental surface

The syncytiotrophoblast is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish nutrient circulation between the embryo and the mother. It is a multinucleate, terminally differentiated syncytium, extending to 13 cm.

<span class="mw-page-title-main">Implantation (embryology)</span> First stage of pregnancy

Implantation, also known as nidation, is the stage in the mammalian embryonic development in which the blastocyst hatches, attaches, adheres, and invades into the endometrium of the female's uterus. Implantation is the first stage of gestation, and, when successful, the female is considered to be pregnant. An implanted embryo is detected by the presence of increased levels of human chorionic gonadotropin (hCG) in a pregnancy test. The implanted embryo will receive oxygen and nutrients in order to grow.

<span class="mw-page-title-main">Decidualization</span> Physiological process in the endometrium

Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy. This includes morphological and functional changes to endometrial stromal cells (ESCs), the presence of decidual white blood cells (leukocytes), and vascular changes to maternal arteries. The sum of these changes results in the endometrium changing into a structure called the decidua. In humans, the decidua is shed during childbirth.

<span class="mw-page-title-main">Uterine gland</span>

Uterine glands or endometrial glands are tubular glands, lined by a simple columnar epithelium, found in the functional layer of the endometrium that lines the uterus. Their appearance varies during the menstrual cycle. During the proliferative phase, uterine glands appear long due to estrogen secretion by the ovaries. During the secretory phase, the uterine glands become very coiled with wide lumens and produce a glycogen-rich secretion known as histotroph or uterine milk. This change corresponds with an increase in blood flow to spiral arteries due to increased progesterone secretion from the corpus luteum. During the pre-menstrual phase, progesterone secretion decreases as the corpus luteum degenerates, which results in decreased blood flow to the spiral arteries. The functional layer of the uterus containing the glands becomes necrotic, and eventually sloughs off during the menstrual phase of the cycle.

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).

<span class="mw-page-title-main">Chorionic gonadotropin beta</span> Protein-coding gene in the species Homo sapiens

Choriogonadotropin subunit beta (CG-beta) also known as chorionic gonadotrophin chain beta is a protein that in humans is encoded by the CGB gene.

<span class="mw-page-title-main">Maternal recognition of pregnancy</span> Crucial aspect of carrying a pregnancy to full term

Maternal recognition of pregnancy is a crucial aspect of carrying a pregnancy to full term. Without maternal recognition to maintain pregnancy, the initial messengers which stop luteolysis and promote foetal implantation, growth and uterine development finish with nothing to replace them and the pregnancy is lost.

<span class="mw-page-title-main">Neohormone</span>

Neohormones are a group of recently evolved hormones primarily associated to the success of mammalian development. These hormones are specific to mammals and are not found in other vertebrates—this is because neohormones are evolved to enhance specific mammalian functions. In males, neohormones play important roles in regulating testicular descent and preparing the sperm for internal fertilisation. In females, neohormones are essential for regulating early pregnancy, mammary gland development lactation, and viviparity. Neohormones superimpose their actions on the hypothalamic-pituitary-gonadal axis and are not associated with other core bodily functions.

References

  1. "Review: Embryonic diapause in the European roe deer – slowed, but not stopped - ScienceDirect".
  2. 1 2 3 4 Lopes FL, Desmarais JA, Murphy BD (December 2004). "Embryonic diapause and its regulation". Reproduction. 128 (6): 669–678. doi: 10.1530/rep.1.00444 . PMID   15579584.
  3. 1 2 3 4 5 Renfree MB, Fenelon JC (September 2017). "The enigma of embryonic diapause". Development. 144 (18): 3199–3210. doi: 10.1242/dev.148213 . PMID   28928280. S2CID   6441064.
  4. Desmarais JA, Bordignon V, Lopes FL, Smith LC, Murphy BD (March 2004). "The escape of the mink embryo from obligate diapause". Biology of Reproduction. 70 (3): 662–670. doi: 10.1095/biolreprod.103.023572 . PMID   14585805. S2CID   38759201.
  5. 1 2 Renfree MB, Shaw G (March 2000). "Diapause". Annual Review of Physiology. 62 (1): 353–375. doi:10.1146/annurev.physiol.62.1.353. PMID   10845095.
  6. Chalar C, Clivio G, Montagne J, Costábile A, Lima A, Papa NG, Berois N, Arezo MJ (2021). "Embryonic developmental arrest in the annual killifish Austrolebias charrua: A proteomic approach to diapause III". PLOS ONE. 16 (6): e0251820. doi: 10.1371/journal.pone.0251820 . PMC   8177498 . PMID   34086690.
  7. Fenelon JC, Banerjee A, Murphy BD (2014). "Embryonic diapause: Development on hold". The International Journal of Developmental Biology. 58 (2–4): 163–174. doi: 10.1387/ijdb.140074bm . PMID   25023682.
  8. 1 2 Ptak GE, Tacconi E, Czernik M, Toschi P, Modlinski JA, Loi P (2012-03-12). "Embryonic diapause is conserved across mammals". PLOS ONE. 7 (3): e33027. Bibcode:2012PLoSO...733027P. doi: 10.1371/journal.pone.0033027 . PMC   3299720 . PMID   22427933.
  9. 1 2 3 4 Murphy BD (December 2012). "Embryonic diapause: Advances in understanding the enigma of seasonal delayed implantation". Reproduction in Domestic Animals. 47 (Supplement 6): 121–124. doi:10.1111/rda.12046. PMID   23279480.
  10. 1 2 3 4 5 6 7 8 9 Deng L, Li C, Chen L, Liu Y, Hou R, Zhou X (November 2018). "Research advances on embryonic diapause in mammals". Animal Reproduction Science. 198: 1–10. doi:10.1016/j.anireprosci.2018.09.009. PMID   30266523. S2CID   52884156.
  11. Aplin JD, Kimber SJ (July 2004). "Trophoblast-uterine interactions at implantation". Reproductive Biology and Endocrinology. 2 (1): 48. doi: 10.1186/1477-7827-2-48 . PMC   471567 . PMID   15236654.
  12. Hussein AM, Balachandar N, Mathieu J, Ruohola-Baker H (September 2022). "Molecular Regulators of Embryonic Diapause and Cancer Diapause-like State". Cells. 11 (19): 2929. doi: 10.3390/cells11192929 . PMC   9562880 . PMID   36230891.
  13. 1 2 3 4 5 Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (April 2020). "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension". Pulmonary Circulation. 10 (1): 167–181. doi:10.1111/een.12792. PMC   7052475 . PMID   32166015. S2CID   202006476.

Further reading