Neurobehavioral alternations of the female offspring born to polycystic ovary syndrome model rats administered by Chinese herbal medicine

Abstract

Background Chinese herbal medicine (CHM) has significant effects that improve the reproductive functions of patients with polycystic ovary syndrome (PCOS). However, the intergenerational effects of CHM on offspring and the underlying mechanism of CHM remain unclear. This study aimed to explore the effects and the underlying mechanism of CHM, specifically the Bu-Shen-Tian-Jing formula (BSTJF), on model rats with polycystic ovary syndrome (PCOS) and the neurobehavioral alterations of female offspring born to PCOS rats administered BSTJF. Methods High-performance liquid chromatography-mass spectrometry (HPLC–MS) and network pharmacology analysis were performed to identify the active ingredients and potential targets of BSTJF. Moreover, PCOS model rats were used to validate the role of BSTJF in reproduction and progeny neural development and to confirm the network pharmacological targets. Results A total of 91 constituents were characterized from BSTJF. The 20 most significant KEGG pathways and the high-frequency genes of these pathways were predicted to be putative targets of these molecules. The rat experiment showed that the downregulation of FOS protein expression in the ovarian granulosa cells of the PCOS group was reversed by BSTJF. The target residence time of the 5-week-old female offspring of the BSTJF group was higher than that of the PCOS group in the water maze experiment. Compared to the PCOS group, the changes in dendritic spine density, ultrastructure of neurons and synapses, and Gabrb1 and Grin2b protein expression levels in the hippocampus of female offspring were partially reversed in the BSTJF group. Conclusions BSTJF can effectively improve ovarian follicle development in PCOS rats and has positive effects on pubertal neurobehavioral alterations in the female offspring of these rats by reversing dendritic spine density, the ultrastructure of neurons and synapses, and the Gabrb1 and Grin2b protein expression levels in the hippocampus.

The neurodevelopment of neonates born to women with polycystic ovary syndrome: evidences from China

“…Concerning neurobehavioral phenotypes, maternal PCOS has been reported to respectively increase the odds of offspring attention-de cit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) by 42% and 59% [13][14][15][16]. Consistently, the previous work of the author's group has suggested a different pattern of brain metrics in PCOS offspring in utero [17], and alterations of neurobehavioral phenotypes in female offspring of both women with PCOS[18] and PCOS model rats [19] which might involve learning and memory. Hence, further study is needed to con rm the role of maternal PCOS in early offspring neurodevelopment for both boys and girls.…”

Bu-Shen-Tian-Jing formulas alleviate the mitochondrial damage induced by oxidative stress in ovarian granulosa cells exposed to DEHP through the HDAC3-HSP90AA pathway

“…Our previous studies have demonstrated that BSTJF1 had positive effects in improving ovarian function (Zhang et al. 2021 ; Pan et al. 2022 ).…”

“…Animal studies have shown that BSTJF1 effectively improves ovarian follicle development in PCOS rats and reduces swollen mitochondria, ruptured mitochondrial cristae, and rough endoplasmic reticulum in progeny born to the BSTJF1 group (Zhang et al. 2021 ). However, the pharmacological effects of BSTJF2 have not been investigated.…”

“…As the bioactive compounds of BSTJF1 and its target proteins have been clarified (Zhang et al. 2021 ), we only conducted integrative network pharmacology analysis for BSTJF2 in the present study in an attempt to determine the underlying signaling pathway.…”

Integrative medicine research for improving female reproductive health during COVID-19

“…Under the complicated and uncertain COVID-19 pandemic, the patient-centered outcome measures could be recommended to be designed and used to assess the effects of integrative medicine on the female reproductive health relevant to the virus. Integrative medicine like Chinese herbal medicine 11 , acupoint hot compress 12 makes great promises in addressing these issues, because the integrative medicine not only has the ability of antivirus, anti-inflammation, immune regulation and organ protection from integrative medicine in management of COVID-19 13 but also can be applied for physical and mental relaxation, anxiety relief and sleep assistance to improve female reproductive health during the COVID-19 pandemic ( Fig. 1 ).…”