Dysregulation of endometrial stromal serotonin homeostasis leading to abnormal phosphatidylcholine metabolism impairs decidualization in patients with recurrent implantation failure.

Study Question: Does abnormal serotonin homeostasis contribute to impaired endometrial decidualization in patients with recurrent implantation failure (RIF)?

Summary Answer: Abnormal serotonin homeostasis in patients with RIF, which is accompanied by decreased monoamine oxidase (MAO) expression, affects the decidualization of endometrial stromal cells and leads to embryo implantation failure.

What Is Known Already: Previous studies have indicated that the expression of MAO, which metabolizes serotonin, is reduced in the endometrium of patients with RIF, and serotonin can induce disruption of implantation in rats. However, whether abnormal serotonin homeostasis leads to impaired decidualization in patients with RIF and, if so, the mechanism involved, remains unclear.

A more natural follicle culture system: Detailed steps of In Vitro 3D follicle culture with alginate gel.

Follicle culture is a process of dividing follicle unit structures from ovaries for continued culture in an incubator, which simulates the environment. Alginate gel is the most stable and most convenient 3D material currently used in follicle culture. We performed follicle culture following the standard operating procedure recommended by the Follicle Handbook and we have summarized our experience and skills in details.

Perfluorooctanoic acid exposure leads to defect in follicular development through disrupting the mitochondrial electron transport chain in granulosa cells.

Perfluorooctanoic acid (PFOA) is a persistent environmental pollutant that can impair ovarian function, while the underlying mechanism is not fully understood, and effective treatments are lacking. In this study, we established a mouse model of PFOA exposure induced by drinking water and found that PFOA exposure impaired follicle development, increased apoptosis of granulosa cells (GCs), and hindered normal follicular development in a 3D culture system. RNA-seq analysis revealed that PFOA disrupted oxidative phosphorylation in ovaries by impairing the mitochondrial electron transport chain.

Decreased LONP1 expression contributes to DNA damage and meiotic defects in oocytes.

Meiotic defects in oocytes are the primary reason for decreased female fertility with advanced maternal age. In this study, we revealed that decreased expression of ATP-dependent Lon peptidase 1 (LONP1) in aged oocytes and oocyte-specific depletion of LONP1 disrupt oocyte meiotic progression accompanying with mitochondrial dysfunction. In addition, LONP1 downregulation increased oocyte DNA damage.

Mitochondrial Transfer from Mouse Adipose-Derived Mesenchymal Stem Cells into Aged Mouse Oocytes.

Due to the decline in the quantity and quality of oocytes related to age, the fertility of women over 35 years of age has declined sharply. The molecular mechanisms that maintain oocyte quality remain unclear, thus it is difficult to increase the birth rate of women over 35 years old at present. Oocytes contain more mitochondria than any type of cell in the body, and any mitochondrial dysfunction can lead to reduced oocyte quality.

Circular RNA circFoxo3 Promotes Granulosa Cell Apoptosis Under Oxidative Stress Through Regulation of FOXO3 Protein.

Oxidative stress leads to ovarian functional decline by inducing granulosa cell (GC) apoptosis. Circular RNA circFoxo3 acts as a critical factor in regulating cell cycle and apoptosis, and cellular senescence in tumor cells. However, function of circFoxo3 is little understood in oxidative stress-induced injury of follicular GCs.

Isolation and Culture of Three Kinds of Umbilical Cord Mesenchymal Stem Cells.

Umbilical cord mesenchymal stem cells (UC-MSCs) are an important cell source for regenerative medicine. UC-MSCs can be isolated from the umbilical cord Wharton's jelly, as well as from the umbilical arteries and umbilical vein. They are known as perivascular stem cells obtained from umbilical arteries (UCA-PSCs), perivascular stem cells obtained from the umbilical vein (UCV-PSCs), and mesenchymal stem cells obtained from Wharton's jelly (WJ-MSCs).

Generation of a Mouse Artificial Decidualization Model with Ovariectomy for Endometrial Decidualization Research.

Endometrial decidualization is a unique differentiation process of the endometrium, closely related to menstruation and pregnancy. Impairment of decidualization leads to various endometrial disorders, such as infertility, recurrent miscarriage, and preterm birth. The development and use of the endometrial decidualization model in reproductive studies have been a highlight for reproductive researchers for a long time.

Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells.

Background: Poor decidualization and abnormal autophagy conditions in the endometria of adenomyosis patients have been reported previously. However, the specific regulatory mechanism of decidualization in adenomyosis and its relationship with autophagy levels have not been clarified.

Methods: Endometrial tissues from adenomyosis patients and uteri from an adenomyosis mouse model were collected for the detection of different expression patterns of KLF4 and autophagy markers (LC3-B/LC3-A and Beclin-1) compared with control groups.

Increased homocysteine regulated by androgen activates autophagy by suppressing the mammalian target of rapamycin pathway in the granulosa cells of polycystic ovary syndrome mice.

The purpose of this study was to explore the potential molecular mechanisms of excess homocysteine in relation to autophagic activity in the ovarian tissue of polycystic ovarian syndrome (PCOS) with hyperandrogenism.A PCOS model was constructed using ICR mice. ELISA was used to detect the Hcy levels in the serum and ovarian tissues of PCOS model.

The mitochondrial protease LONP1 maintains oocyte development and survival by suppressing nuclear translocation of AIFM1 in mammals.

Background: Oogenesis is a fundamental process of human reproduction, and mitochondria play crucial roles in oocyte competence. Mitochondrial ATP-dependent Lon protease 1 (LONP1) functions as a critical protein in maintaining mitochondrial and cellular homeostasis in somatic cells. However, the essential role of LONP1 in maintaining mammalian oogenesis is far from elucidated.

Attenuated monoamine oxidase a impairs endometrial receptivity in women with adenomyosis via downregulation of FOXO1†.

The establishment of endometrial receptivity is a prerequisite for successful pregnancy. Women with adenomyosis possess a lower chance of clinical pregnancy after assisted reproductive technology, which is partially due to impaired endometrial receptivity. The establishment of endometrial receptivity requires the participation of multiple processes, and proper endometrial epithelial cell (EEC) proliferation is indispensable.

Transplantation of human endometrial perivascular cells with elevated CYR61 expression induces angiogenesis and promotes repair of a full-thickness uterine injury in rat.

Background: Disruptions of angiogenesis can have a significant effect on the healing of uterine scars. Human endometrial perivascular cells (CD146+PDGFRβ+) function as stem cells in the endometrium. Cysteine-rich angiogenic inducer 61 (CYR61) plays an important role in vascular development.

Transplantation of umbilical cord-derived mesenchymal stem cells on a collagen scaffold improves ovarian function in a premature ovarian failure model of mice.

Premature ovarian failure (POF) is a refractory disease; one of the most important goals of treatment is to improve fertility. In the study, collagen scaffold loaded with human umbilical cord-derived mesenchymal stem cells (collagen/UC-MSCs) transplantation in POF mice preserved ovarian function, as supported by increased estrogen (E) and anti-Mullerian hormone (AMH) levels, increased ovarian volume, and an increased number of antral follicles. Immunohistochemistry results of Ki67 indicated transplantation of collagen/UC-MSCs promoted granulosa cell proliferation, which is crucial to oocyte maturation and follicular development.

Mitochondrial transfer from aged adipose-derived stem cells does not improve the quality of aged oocytes in C57BL/6 mice.

Female fertility declines dramatically over the age of 35 due to age-related decreases in oocyte quality and quantity. Although mitochondrial transfer promises to be a technology that can improve the quality of such age-impaired oocytes, the ideal mitochondrial donor remains elusive. In the present study, we aimed to identify whether aged adipose-derived stem cells constitute an excellent mitochondrial donor that would improve the quality of aged mouse oocytes.

Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility.

Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles.