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Pharmaceutical composition for regulating and controlling reserve of primordial follicle

A technology of primordial follicles and compositions, applied in drug combinations, active ingredients of hydroxyl compounds, pharmaceutical formulas, etc., can solve problems such as unreported treatment methods, and achieve the effects of avoiding the risk of birth defects, maintaining fertility, and delaying decline

Inactive Publication Date: 2021-02-26
SOUTH CHINA UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of ATRA to regulate the activation of primordial follicles and its use as a treatment for ovarian reserve preservation in vivo has never been reported.

Method used

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  • Pharmaceutical composition for regulating and controlling reserve of primordial follicle
  • Pharmaceutical composition for regulating and controlling reserve of primordial follicle
  • Pharmaceutical composition for regulating and controlling reserve of primordial follicle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1. Expression pattern of ATRA synthetase, receptor and catabolic enzyme in neonatal mouse ovary

[0061] First, the expression characteristics of ATRA signaling molecules in primordial follicles were detected by RT-qPCR, immunofluorescence and Western blot methods, and it was found that ATRA synthetase was mainly expressed in pregranulosa cells; ATRA receptors were mainly expressed in oocytes; ATRA The degrading enzymes are expressed in both pregranulosa cells and oocytes ( figure 1 ).

Embodiment 2

[0062] Example 2.ATRA inhibits the activation of neonatal mouse ovarian primordial follicles

[0063] In order to study the effect of ATRA on the activation of primordial follicles, the ovaries of 3dpp neonatal mice were cultured for 4 days with or without drug addition, and the ovarian structure was observed. Statistical analysis of serial sections showed that ATRA could significantly inhibit small The activation of primordial follicles in mice (116.7±4.4); while ATRA synthase inhibitors (443.3±19.2) and receptor inhibitors (400.0±10.4) can significantly increase the activation of primordial follicles ( figure 2 ).

[0064] The physiological role of ATRA was further studied. The newborn mice were injected intraperitoneally with ATRA or talarazole once a day for a total of 4 days. Different from ovaries cultured in vitro, RT-qPCR and Western blot analysis showed that injection of ATRA could not increase the gene and protein levels of metabolic enzymes in mouse ovaries. St...

Embodiment 3

[0065] Example 3. Oral administration of ATRA can increase the number of primordial follicles in the adult mouse ovary

[0066] The effect of oral administration of ATRA on primordial follicle activation in adult mice was further tested. After serial section analysis, the number of primordial follicles (2395.0±65.6) in the 500ng / mL ATRA group was significantly higher than that in the control group (0 ng / mL group, 1996.7±54.9), and correspondingly the number of growing follicles in the 500ng / mL ATRA group (617.0 ±37.1) significantly lower than the control group (229.0±100.6) ( Figure 3a-3f ). At the same time, 500ng / mL ATRA had no significant effect on the opening of the vaginal opening, the length of the estrus cycle and the regularity of estrus in mice (P>0.05) ( Figures 3a-3c ). Therefore, 500ng / mL of ATRA is an appropriate oral concentration, and it was chosen for subsequent experiments. Next, the effect of oral administration of ATRA for 1 to 5 months on follicular d...

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Abstract

The invention provides a pharmaceutical composition for regulating and controlling reserve of primordial follicle. The pharmaceutical composition comprises therapeutically effective amount of all-trans retinoic acid. Furthermore, the invention also provides a method for regulating and controlling reserve of primordial follicle and new pharmaceutical application of all-trans retinoic acid. The invention provides a new means for maintaining fertility.

Description

technical field [0001] The present invention generally relates to the technical field of pharmacy, and specifically relates to a pharmaceutical composition for regulating primordiafollicle reserve, a method for regulating primordiafollicle reserve, and a new pharmaceutical application of all-trans retinoic acid. Background technique [0002] At present, the fertility of people of childbearing age is declining globally. Conventional assisted reproductive technologies such as artificial insemination, in vitro fertilization, and embryo transfer can address the fertility needs of some infertile patients. In addition, late marriage and late childbearing have become a social demand. However, aging causes a gradual decrease in the reserve of germ cells in the ovaries, which leads to a decline in fertility. On the other hand, there are more and more cancer patients, and they are getting younger. However, chemotherapy drugs can cause damage to germ cells, which can lead to decreas...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/203A61K31/436A61K31/122A61K31/428A61P15/08
CPCA61K31/122A61K31/203A61K31/428A61K31/436A61K45/06A61P15/08A61K2300/00
Inventor 张美佳严杰刘涛郑娜娜张晓丹赵瑜
Owner SOUTH CHINA UNIV OF TECH
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