ABSTRACT
ObjectiveTo study the changes of mitochondrial function of ovarian granulosa cells in women of different ages and the effect of Erzhi-Tiangui prescription on in vitro fertilization-embryo transfer （IVF-ET） outcomes for elderly women， so as to verify the connotation of the "Seven-Seven" theory in the Huangdi's Internal Classic （《黄帝内经》）. MethodA total of 150 infertility patients undergoing IVF-ET at the Reproductive and Genetic Center of Integrative Medicine， Affiliated Hospital of Shandong University of Traditional Chinese Medicine were recruited and assigned into "hree-Seven/Four-Seven （30 cases）， Five-Seven （60 cases）， and Six-Seven （60 cases） groups according to the "Seven-Seven" theory. The Five-Seven and Six-Seven groups were further assigned into control and Chinese medicine subgroups using the random number plus envelope method， and the Chinese medicine group was administrated with Erzhi Tiangui prescription from the start day of controlled ovulation stimulation cycle to the trigger day. The IVF outcome was observed， and Western blot was employed to determine the levels of mitofusin 1 （MFN1）， mitofusin 2 （MFN2）， and dynamin-related protein 1 （Drp1） in the ovarian granulosa cells. ResultCompared with the Three-Seven/Four-Seven group， the control subgroups of the Five-Seven and Six-Seven groups showed decreased retrieved oocytes， two pronuclear （2PN） embryos， available embryos， high-quality embryos， clinical pregnancy rate， and live birth rate （P<0.05）. Moreover， the control subgroup of the Six-Seven group showed decreased fresh embryo transfer rate（P<0.05）. Compared with the control subgroup of the Five-Seven group， that of the Six-Seven group showed reduced retrieved oocytes， 2PN embryos， available embryos， high-quality embryos， and clinical pregnancy rate （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， 2PN oocytes， and available embryos than the control subgroup in the Five-Seven groups （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， than the control subgroup in the Six-Seven groups （P<0.05）. The control subgroup of the Six-Seven group showed lower expression levels of Mfn1 and Mfn2 and higher level of Drp1 than the control subgroup of the Five-Seven group （P<0.05）， which indicated that the levels of Mfn1 and Mfn2 in ovarian granulosa cells were down-regulated while the expression of Drp1 was up-regulated with aging （P<0.05）. The Chinese medicine subgroup had higher Mfn2 level and lower Drp1 level than the control subgroup in the Five-Seven group （P<0.05）， and the Chinese medicine subgroup had higher Mfn1 and Mfn2 levels and lower Drp1 level than then control subgroup in the Six-Seven group （P<0.05）. ConclusionsThe prognosis of IVF in women after "Five-Seven" became worse with aging， and the mitochondria in ovarian granulosa cells showed decreased fusion ability and increased fission， which verified the connotation of the "Seven-Seven" theory from the mitochondrial function. Erzhi Tiangui prescription can regulate the mitochondrial function of ovarian granulosa cells in elderly women， up-regulate the expression levels of Mfn1 and Mfn2 to promote mitochondrial fusion， and down-regulate the expression of Drp1 to reduce mitochondrial fission， thus alleviating the ovarian hypofunction caused by aging， improve the development potential of oocytes， and improve the IVF outcomes of elderly women. However， this prescription has limited efficacy for the elderly women in the age range of "Six-Seven".
ABSTRACT
As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing-nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected.
Subject(s)
Humans , Drugs, Chinese Herbal , Pharmacology , Kidney , Medicine, Chinese Traditional , Regenerative Medicine , Stem CellsABSTRACT
Objective: To investigate the mechanisms through which kidney-tonifying herbs (KTHs) and liver-clearing herbs (LCHs) in Dingjing Decoction (DJD) regulate premature ovarian failure (POF). Methods: One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results: The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol (CORT) in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms. Gonadotropin-releasing hormone (GnRH), which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion: KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. GnRH is the key biological molecule associated with KTHs intervention.
ABSTRACT
Primary osteoporosis (POP) is one of the most common diseases in the elderly people resulting in high risk of fracture and poor quality of life. In addition to the pathological changes in bone mass, most of the POP patients also suffer from Chinese medicine (CM) syndromes of Shen (Kidney) essence deficiency. Shen essences are highly related to bone. Shen essence deficiency plays an important part in the development of POP and a better diagnosis of POP could be made by combining CM syndromes with Western medicine risk factors. Treatments of POP should aim at both increasing the bone mass and relieving the syndromes of Shen essence deficiency. Clinical study confirmed that treating POP patients with Shen-tonifying herbs could increase the bone mass and relieve the CM syndromes of POP patients. Basic researches clarified the mechanism by which Shen-tonifying herbs increased bone mass in animal models. The mechanisms by which Shentonifying herbs relieve the CM syndromes are still in investigation.