Effects of Perinatal Estrogen Exposure on Fertility and Cancer in Mice

Author(s):  
Retha R. Newbold
Keyword(s):  
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sebastian Ganz ◽  
Axel Wehrend

Abstract Background Clinical signs of heat in bitches that have been previously spayed are often associated with the presence of ovarian remnant syndrome. The inclusion of exogenous estrogens as a differential diagnosis in this regard is often ignored and may lead to misinterpretation of the case. Case presentation Herein, we report a case of exogenous estrogen exposure over several months to a 6.5-year-old spayed crossbred bitch, weighing 8.4 kg. The bitch presented in the clinic because of suspected ovarian remnant syndrome. Castration was performed within the first 6 months after birth. Important endocrine parameters measured at the first appointment were Anti-Müllerian hormone (< 0.01 ng/mL), progesterone (0.36 ng/mL), estradiol-17ß (20.7 pg/mL), and luteinizing hormone (< 0.1 ng/mL). After an extensive conversation with the owner, it was revealed that she was using an estrogen spray because of severe menopausal symptoms. After the owner stopped using this spray, the symptoms of the bitch disappeared. Conclusion Therefore, the uptake of estrogens should be a differential diagnosis for symptoms of the ovarian remnant syndrome. A detailed anamnesis is crucial to identify the source of estrogen in the environment of the affected bitch.


Author(s):  
Dariusz Szukiewicz ◽  
Aleksandra Stangret ◽  
Carmen Ruiz-Ruiz ◽  
Enrique G. Olivares ◽  
Olga Soriţău ◽  
...  

AbstractEndometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2370
Author(s):  
JooYong Park ◽  
Ji-Yeob Choi ◽  
Jaesung Choi ◽  
Seokang Chung ◽  
Nan Song ◽  
...  

In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.


2017 ◽  
Vol 102 (12) ◽  
pp. 4588-4595 ◽  
Author(s):  
Natalia Hetemäki ◽  
Hanna Savolainen-Peltonen ◽  
Matti J Tikkanen ◽  
Feng Wang ◽  
Hanna Paatela ◽  
...  

Abstract Context In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. Objective We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. Design, Setting, Patients, and Interventions AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Results Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Conclusions Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.


2011 ◽  
Vol 2 (1) ◽  
pp. 9-16 ◽  
Author(s):  
C. Sonnenschein ◽  
P. R. Wadia ◽  
B. S. Rubin ◽  
A. M. Soto

The discovery of a rare clear cell carcinoma of the vagina in young women gestationally exposed to the estrogen diethylstilbestrol (DES) lent empirical support to the hypothesis that prenatal exposure to xenoestrogens might cause cancer. This fact contradicted two well-accepted notions: (i) mammalian development was merely the unfolding of a genetic program and (ii) only mutagenic agents could cause cancer. The ecological developmental biology (eco–devo) movement revitalized the concept of developmental plasticity through the occurrence of polyphenisms whereby a single genotype produces diverse phenotypes which are determined by environmental cues. Based on the principles of eco–devo and the tissue organization field theory of carcinogenesis, we hypothesized that developmental exposure to xenoestrogens increased the propensity to develop mammary cancer during adulthood. Bisphenol-A (BPA), a ubiquitous xenoestrogen, was chosen as a model for environmental estrogen exposure. In mice, perinatal exposure to environmentally relevant BPA levels induced alterations of the mammary gland architecture which manifested during fetal morphogenesis and throughout life, including the development of pre-neoplastic lesions. In rats, gestational exposure to BPA induced pre-neoplastic lesions and carcinoma in situ that manifested in adulthood in the absence of any additional treatment. Emerging epidemiological data reveal an increased incidence of breast cancer in women exposed to DES during gestation. Hence, both animal experiments and epidemiological data strengthen the hypothesis that fetal exposure to xenoestrogens may be an underlying cause of the increased incidence of breast cancer observed over the past 50 years.


2021 ◽  
Vol 235 ◽  
pp. 105807
Author(s):  
Gregory P. Toth ◽  
David C. Bencic ◽  
John W. Martinson ◽  
Robert W. Flick ◽  
David L. Lattier ◽  
...  
Keyword(s):  

2012 ◽  
Vol 4 (2) ◽  
pp. 75-84 ◽  
Author(s):  
Piyush Kumar ◽  
Jai Kishan Goel

ABSTRACT Endometrial cancer is the most common gynecological cancer in developed countries and second most common in developing countries. Its incidence is increasing in postmenopausal women. Factors related to chronic estrogen exposure are associated with a higher incidence. Abnormal uterine bleeding is the cardinal symptom. All women with suspected endometrial cancer require transvaginal ultrasonography and most will undergo endometrial biopsy; more sophisticated radiological examinations are required for preoperative staging. The general approach for treatment of endometrial cancer is hysterectomy, bilateral salpingo-oophorectomy, abdominopelvic washings, lymph node evaluation and maximal surgical cytoreduction for those with advanced disease. Postoperative adjuvant therapy [vaginal brachytherapy, external beam radiation therapy (RT), chemotherapy] may be recommended depending on the estimated risk of recurrence. Individual patient characteristics and surgical as well as pathologic staging are the main factors that are used for postsurgical risk stratification, which in turn, directs the selection of adjuvant treatment. How to cite this article Goel JK, Kumar P. Cancer Endometrium: An Update. J South Asian Feder Obst Gynae 2012;4(2):75-84.


Sign in / Sign up

Export Citation Format

Share Document