Sustained obesity reduces litter size by decreasing proteins regulating folliculogenesis and ovulation in rats - A cafeteria diet model Saranya Kannan, Ravi Sankar Bhaskaran * Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India article info Article history: Received 30 August 2019 Accepted 8 September 2019 Available online 13 September 2019 Keywords: Sustained obesity Cafeteria diet Fertility Folliculogenesis Ovulation Litter size abstract Global rise in obesity at early age due to overconsumption of energy-dense food is the major health problem which increases the exposure to obesity over longer duration. Recently we reported that the severity of ovarian dysfunction depends on the duration of obesity. In the present study, we examined the consequences of sustained obesity on reproductive outcome and the underlying mechanism. Sprague Dawley female rats (21 days old) were fed ad libitum with a standard diet (control group) and a cafeteria diet (Obese group) for 32 weeks. We observed hypoprolactinemia, sub-fecundity, sub-fertility, delayed conception and macrosomic pups of reduced litter size in sustained obese rats. The observed decrease in the number of ovarian follicles (primordial, primary, secondary and antral follicles) and corpus luteum indicates impairment in folliculogenesis and ovulation. This impairment might be due to decreased level of ovarian proteins (PRLR, AR, GDF-9, OCT-4, COX-2, PPARg, ER and PR subtypes) in obese rats. We conclude that sustained obesity impaired folliculogenesis and ovulation thereby increased the severity of reproductive deficits. © 2019 Elsevier Inc. All rights reserved. 1. Introduction According to WHO the energy imbalance between calories consumed and expended resulted in three fold increase in the worldwide prevalence of obesity since 1975 [1]. This remarkable rise in obesity rates has led to coequal rise in the duration of obesity over the average individual's lifetime known as long-term obesity [2]. This ongoing upward trend in obesity resulted in parallel rise in the associated comorbidities, including infertility. Eating habits are closely associated with the quality of women's reproductive life [3], surfeit and deficit of energy are associated with greater risk of reproductive disorders [4]. Palatability plays the key role in promoting hedonic hunger contributing to overeating which is the major factor involving in the disruption of the energy balance [5] that results in obesity [6]. Consumption of cafeteria diet (CAFD) increase energy intake and cause obesity in humans [7] and used as the experimental model for the study of obesity since late seventies in which animals were given free access to high energy, palatable, self-selected diets [8,9]. In rodents, CAFD model more closely re- flects the modern human condition of early onset obesity [10]. Across the reproductive spectrum, obesity is linked with enor- mous risk of adverse reproductive health outcomes such as ovulatory disorders, decreased rate of conception, early pregnancy loss, reduced assisted reproductive technology success, congenital abnormalities and infertility [11 , 12] suggestive of derangements in ovarian folliculogenesis and steroidogenesis. Children consume large amount of energy-dense palatable food at very early age leading to increased exposure to obesity over longer duration. It has been reported that the reproductive dis- turbances appears to be more in early-onset obesity [13]. So far the consequences of CAFD-induced obesity on reproductive disorders were studied in short-term (8 weeks) CAFD fed animals [14e16]. We recently reported the association between duration of obesity and severity of ovarian dysfunction by comparing short-term and long-term obesity [17]. Although both the duration of CAFD feeding induced obesity in rats, the severity of comorbidities associated with diet-induced obesity is more in the long-term (32 weeks) obese animals. Short-term (20 weeks) obese animals showed the hormonal profile commonly reported in obese individuals with reproductive disorders. On the other hand, long-term obese ani- mals showed hypoinsulinemia and hypogonadotropic hypogonad- ism [17]. Further, we suggested that long-term CAFD-induced * Corresponding author. Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India. E-mail addresses: saranyakalai.kanan@gmail.com (S. Kannan), bravisankar@ yahoo.com (R.S. Bhaskaran). Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc https://doi.org/10.1016/j.bbrc.2019.09.025 0006-291X/© 2019 Elsevier Inc. All rights reserved. Biochemical and Biophysical Research Communications 519 (2019) 475e480