Congenital ovarian development insufficiency

　　First, physical factors

　　1. After World War II, with the advent of the 'Atomic Age', the use of atomic energy in human activities has increased, and atomic energy has become an indispensable means in scientific research, medicine, and the development of agriculture and industry. The development and testing of nuclear weapons and human exploration of outer space have made ionizing radiation an important factor affecting all humanity and the entire organic world.

　　2. The radiation environment in which humans live includes natural radiation and artificial radiation. Natural radiation includes cosmic radiation, terrestrial radiation, and radiation from radioactive substances within the human body, while artificial radiation includes medical exposure and occupational exposure, etc.

　　3. Ionizing radiation is notable for causing chromosome non-separation. Experiments have shown that when comparing oocytes at the MⅡ stage of irradiated mice with those of non-irradiated mice of the same age, non-separation is significantly higher in the irradiated group, and this phenomenon is particularly evident in older mice. In humans, lymphocytes exposed to radiation or grown in irradiated serum show a higher frequency of trisomy in the experimental group compared to the control group. It also causes chromosomal abnormalities such as double crossovers and deletions. There are also reports that mothers exposed to ionizing radiation have a significantly higher risk of giving birth to children with Down syndrome.

　　4. Chemical factors: People are exposed to various types of chemical substances in daily life, some of which are natural products and others are synthetically produced. They enter the human body through pathways such as diet, respiration, or skin contact. In addition, many chemical drugs, toxins, and antimetabolites can cause chromosomal abnormalities. Other alkylating agents such as nitrogen mustard and ethylene oxide can also cause chromosomal abnormalities.

　　5. Biological factors: When cells in culture are treated with viruses, they often cause various types of chromosomal abnormalities, including breaks, fragmentation, and exchanges. Transformation by infecting with transforming viruses can convert diploid cells into aneuploid cells; at the same time, another special phenomenon occurs: the cell population in culture, which originally has a limited lifespan, can be cultured indefinitely once it is transformed. Mycoplasma can cause changes in chromosomes, so when cultured cells are used for cytogenetic diagnosis, one should be vigilant about mycoplasma infection.

　　6. The epidemiological evidence of virus-induced chromosome damage shows that in patients with infectious mononucleosis, epidemic parotitis, rubella, chickenpox, chronic active hepatitis, and other patients with no specific diagnosis, virus infection is usually involved. In the lymphocyte cultures of these individuals, various types of chromosomal abnormalities are often observed. Individuals vaccinated with live attenuated viruses to resist yellow fever also show obvious chromosomal pre-damage in their lymphocyte cultures.

　　7. The fetal effect of maternal age: at 6 to 7 months of gestation, all oogonia have developed into primary oocytes and entered the prophase of the first meiotic division, moving into the nuclear envelope stage. At this time, the chromosomes are re-loosened and expanded, resembling an interphase nucleus, and this state continues until before puberty when ovulation occurs. This condition may be related to the synthesis of yolk. By puberty, due to the cyclic stimulation of follicle-stimulating hormone (FSH), only one oocyte completes the first polar body each month. The secondary oocyte is released from the ovary, enters the fallopian tube, and undergoes the second meiotic division to reach the metaphase. If fertilization occurs at this time, the ovum will complete the second meiotic division, becoming a mature ovum, and combine with sperm to form a zygote, thereby initiating the development of a new individual until birth. From the above process, it can be known that women are born with all their eggs, and from puberty onwards, they can only release one egg each month from the existing eggs, totaling hundreds of eggs in a lifetime. This also suggests that as women age, the age of the eggs they release also increases. With the increase of maternal age, under the influence of many factors both inside and outside the mother, eggs may also undergo many aging changes, affecting the interaction between homologous chromosomes during maturation division and the behavior during the late stage of division, leading to the non-separation of chromosomes.

　　8, Genetic factors Chromosomal abnormalities may show a familial tendency, suggesting that chromosomal畸变 is related to genetics. Humans may have genes prone to nondisjunction, and other organisms also have similar genes. It is reported that in the same family, there may be patients with the same or different types of aneuploidy. In addition, chromosomal abnormal parents can pass on to the next generation in different ways. The most obvious example is some carriers of balanced translocations, which can cause offspring with chromosomal abnormalities or normal offspring, among which those involving D, G group chromosomes are more common because they are acrocentric chromosomes, forming centromere cohesion during mitosis, which may be one of the causes of chromosomal nondisjunction.

　　9, Autoimmune diseases Autoimmune diseases seem to play a certain role in chromosomal nondisjunction, such as the close correlation between increased primary autoimmune antibodies in the thyroid and familial chromosomal abnormalities.

　　Two, Pathogenesis

　　1, In diploid organisms, each normal gamete, whether sperm or egg, contains all the chromosomes, which is called a chromosome set. For example, the chromosome set of normal gametes in humans contains 22 + X or 22 + Y, and is called haploid (haploid, n). The zygote is formed by the fusion of a sperm containing one chromosome set and an egg containing one chromosome set. Therefore, the individual developed from the zygote has two chromosome sets, known as diploid (diploid, 2n).

　　2, Numerical anomalies If the addition or deletion of a whole set of chromosomes or a whole chromosome in a normal diploid is called chromosomal numerical anomaly, including euploidy and aneuploidy.

　　3, Congenital ovarian dysgenesis is a chromosomal number anomaly in the monosomy of exoanomaly.

　　4, Aneuploidy: It refers to the addition or deletion of individual chromosomes or segments within a diploid. This includes monosomy and polysomy.

　　5, The karyotype 45, X with gonadal dysgenesis (Turner syndrome) is the most typical example of monosomy in humans. Monosomy refers to a condition where the number of chromosomes is less than diploid, hence also known as subdiploid. Since individuals with monosomy lack a chromosome, it leads to severe gene deficiency. Therefore, even smaller monosomy of the 21st and 22nd chromosomes on autosomes is difficult to survive. Some cases with 45, X karyotype may survive, but the majority of fetuses (about 98%) are aborted in the embryonic stage. Survivors may have a female phenotype, but due to the lack of one X chromosome, the female ovaries cannot develop normally, most cannot form germ cells, the external genitalia do not develop, and secondary sexual characteristics are lacking. In addition, patients may have malformations such as short stature, webbed neck, and radial clubfoot.

　　6, The formation mechanism of aneuploidy: The main cause of aneuploidy is the separation or loss of chromosomes during cell division.

　　1, Congenital ovarian hypoplasia in children is often accompanied by short stature and low weight, and may be accompanied by cardiac malformations, renal malformations, and so on.

　　2, Cardiac malformations: More common in congenital heart malformations. Congenital heart malformations belong to congenital heart diseases and are one of the common congenital malformations in fetuses, with an incidence rate of about 0.4-0.8%. The majority of fetuses with chromosomal abnormalities and many fetuses with severe malformations also have cardiac malformations.

　　3, Renal malformations include the following situations: one, solitary kidney; two, underdeveloped kidney; three, duplicated kidney; four, accessory kidney; five, hereditary polycystic kidney disease; six, simple renal cyst; seven, multicystic dysplastic kidney; eight, local multicystic cysts within the kidney.

　　1, The clinical characteristics are short stature, underdeveloped reproductive organs and secondary sexual characteristics, and a group of somatic developmental abnormalities. The height is generally below 150cm. In females, the vulva is underdeveloped, with a vagina, a small uterus, or absence of the uterus. The body features include multiple moles, ptosis of the eyelids, large ears with low placement, high palate arch, low posterior hairline, short and wide neck, with neck webbing, barrel-shaped or shield-shaped chest, wide nipple spacing, undeveloped breasts and nipples, genu varum, short fourth or fifth metacarpal or phalanges, palm prints of the通关 hand, lymphedema of the lower limbs, renal malformation, aortic arch stenosis, and so on. These features are not necessarily present in every patient, the degree of intelligence development varies, with some completely normal and others with poor intelligence. The lifespan is the same as that of normal people. The age of the mother seems to be unrelated to this developmental abnormality. LH and FSH levels significantly increase from the age of 10 to 11, and the increase in FSH is greater than that in LH. Peking Union Medical College Hospital measured bone density in 40 patients with Turner syndrome using single-photon absorptiometry (SPA), and 13 of them also used QCT to measure bone density, finding that the bone density of Turner patients was significantly lower than that of normal women of the same age.

　　2, Turner syndrome chromosomes, except 45, X, can have various mosaics, such as 45, X/46, XX, 45, X/47, XXX, or 45, X/46, XX/47, XXX, etc. The clinical manifestations depend on which cell line in the mosaicism is predominant. If normal sex chromosomes are predominant, the abnormal signs are fewer. Conversely, if abnormal chromosomes are predominant, the typical abnormal signs are also more numerous.

　　3, Turner syndrome can also be caused by structural abnormalities of sex chromosomes, such as the isochromosome Xi(Xq) of the long arm of the X chromosome, the isochromosome Xi(Xp) of the short arm, the absence of the long or short arm XXq-, XXp-, forming a circular Xxr (Figure 8) or translocation. The clinical manifestations are related to the degree of absence. Those with absence can still have residual follicles and have menstrual periods, but they will eventually become amenorrheic after several years.

　　4, Laparotomy can reveal the female internal reproductive organs, which are all small, with string-like gonads that are 2-3 cm long and 0.5 cm wide, located at the site equivalent to the ovary. Under microscopic observation, it can be seen that there is thin cortex, medulla, and hilum within the string. The cortex contains typical ovarian stroma, with cells in long wavy shape, and the hilum has hilum cells and ovarian rete. By the 12th week of pregnancy, the 45, X embryo has a normal number of primordial follicles, which decrease in number as the fetus grows larger, and almost none at birth. Clinically, some patients can become pregnant and give birth, but their reproductive lifespan is short, and they have early ovarian failure, which may be related to the slower consumption rate of their oocytes during embryonic development. Therefore, it is very important to understand which patients with Turner syndrome have follicles and can reproduce. The karyotype of pregnant cases is 45, X/46, XX mosaicism. When the 46, XX cell line is predominant, the ovary can develop and maintain normal function. Literature reports that 8% of 45, X individuals and 21% of 45, X/46, XX individuals can have normal pubertal development and menstruation. When the ovary is without follicles and lacks function, the pituitary gonadotropin FSH and LH increase. A few patients with Turner syndrome do not increase FSH and LH but are within the normal range. Laparoscopic examination has found that such patients have small ovaries, and live examination shows that there are follicles in the ovaries. If patients with Turner syndrome can become pregnant, they have a high rate of miscarriage and stillbirth. A large number of 45, X zygotes cannot develop and result in miscarriage, accounting for 5.5% to 7.5% of miscarriages.

　　5, In 1971, Andrews proposed that the absence or mosaicism of sex chromosomes not only affects the development of the gonads and reproductive tract, but also affects the somatic abnormal features of Turner syndrome. If one X chromosome is missing, in addition to the underdevelopment of the gonads, there are various somatic abnormal manifestations of Turner syndrome, such as the absence of the short arm of X, which also has the characteristics of Turner syndrome. The absence of the long arm only has a string-like gonad without somatic abnormalities. In 1972, Neu et al. also believed that the short stature of Turner syndrome was related to the absence of the short arm. Individuals with sex chromosomes X, XXp-, or XXqi are all short-statured. When the long arm of sex chromosome X is lost, such as XXq- or XXpi, there are only amenorrhea and string-like gonads without short stature and other abnormalities of Turner syndrome. Therefore, it is believed that the differentiation of ovaries and oocytes requires two sites on the sex chromosomes, one on the long arm and the other on the short arm. The loss of any one of them will cause incomplete development of the gonads, and abnormal development of height and gonads is related to both the long and short arms. Normal height requires both the long and short arms, but the short arm plays a decisive role. The same is true for the gonads, but the long arm plays a major role.

　　One, Daily Prevention Measures for Congenital Ovarian Hypoplasia

　　24. Prohibition of marriage between close relatives.

　　23. Pre-marital examination to discover genetic diseases or other diseases that should not be married.

　　22. The detection of carriers is determined through means such as mass screening, family investigation and pedigree analysis, and laboratory tests to determine whether it is a genetic disease and to determine the mode of inheritance, etc.

　　Four, Genetic Counseling

　　38. 1, Patients diagnosed with genetic diseases and their relatives.

　　37. 2, Families with recurrent diseases of unknown cause.

　　36. 3, Congenital primary intellectual disability, suspected to be related to heredity.

　　Patients with congenital ovarian hypoplasia need to undergo the following corresponding examinations: hormone level detection, karyotype examination, bone mineral density examination. Colposcopy, laparoscopy. Formulate a treatment plan according to the results of the examination.

　　Therapeutic Recipes for Congenital Ovarian Hypoplasia

　　29. 1, Erxian Lamb Soup, 12 grams each of Xianmao and Xianlingpi, 15 grams of ginger, 250 grams of lamb, a little salt, cooking oil, and monosodium glutamate. Cut the lamb into slices, put it in a pot with an appropriate amount of water, then put the Xianmao, Xianlingpi, and ginger wrapped in gauze into the pot, boil the lamb over low heat until tender, add the ingredients and it is ready, remove the medicine bag when eating, eat the meat and drink the soup. This ovarian maintenance food therapy method has the effect of nourishing the kidney.

　　28. 2, Shanyu Lean Meat Soup, 50 grams each of fish bladder and lean pork, 20 grams each of Chinese wolfberry and Taiizi参, 18 grams of raw earth. Soak the fish bladder in clean water to soften, cut into strips; wash the lean pork, slice; wash the other ingredients. Put all the ingredients in a pot, add an appropriate amount of water, boil over low heat for 1-2 hours, add salt to taste, drink the soup and eat the fish bladder, Chinese wolfberry and lean pork, finish within a day. It has the effect of nourishing yin and reducing fire, helping women to maintain the health of the ovaries.

　　Congenital ovarian hypoplasia is a sex chromosome disease, the etiology is still unclear, refer to the relevant preventive measures for genetic diseases:

　　24. Prohibition of marriage between close relatives.

　　23. Pre-marital examination to discover genetic diseases or other diseases that should not be married.

　　22. The detection of carriers is determined through means such as mass screening, family investigation and pedigree analysis, and laboratory tests to determine whether it is a genetic disease and to determine the mode of inheritance, etc.