International Scholarly Research Network ISRN Endocrinology Volume 2011, Article ID 863403, 7 pages doi:10.5402/2011/863403 Research Article Infertility in WNIN Obese Mutant Rats —Causes? Nemani Harishankar, 1 Punjal Ravinder, 2 K. Madhavan Nair, 2 and Nappanveettil Giridharan 1 1 National Centre for Laboratory Animal Sciences, National Institute of Nutrition, Indian Council of Medical Research (ICMR), Jami-Osmania PO, Andhra Pradesh, Hyderabad 500 007, India 2 Micronutrient Research Group, Biophysics Division, National Institute of Nutrition, Indian Council of Medical Research (ICMR), Hyderabad 500 007, India Correspondence should be addressed to Nappanveettil Giridharan, nappanveettil@yahoo.co.in Received 14 September 2011; Accepted 1 November 2011 Academic Editors: J. A. Rillema and E. Spinedi Copyright © 2011 Nemani Harishankar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We are maintaining two obese mutant rat strains (WNIN/Ob and WNIN/GR-Ob) in our animal facility since 1997. These rat colonies are perpetuated by crossing heterozygous littermates, since the obese phenotypes of both genders turned out be infertile. The present study revealed the reasons for this infertility. The male obese rats, though appeared normal in terms of sperm count, sperm motility and testis histology, however found wanting in terms of libido. This appeared to be due to low circulating testosterone levels seen in these animals, which should also account for low testis and accessory gland weights seen in them. The females exhibited delayed puberty, in terms of days taken for opening of vagina, irregular oestrus cycles and had small ovaries and short and stumpy uterine horns. The FSH peak observed in control lean animals during oestrus stage of the sexual cycle and also the E2 peak of normal oestrus cycle was conspicuously absent in these animals. They also showed elevated levels of progesterone throughout the sexual cycle. Thus the infertility seen in these mutants could be attributed to their abnormal gonadosteroid levels and the resulting anatomical and physiological defects. 1. Introduction We are maintaining two obese mutant rat strains in our animal facility since 1997, derived from our Wistar (WNIN) stock. These are unique in certain aspects in comparison to similar rodent models of obesity established in the West [1– 3]. The prominent differences are the presence of a unique “kinky tail” in homozygous obese (−/−) and heterozygous carriers (+/−) and the mode of its inheritance, that is, auto- somal incomplete dominance [2]. However, like other obese rodent models reported so far, WNIN/Ob and WNIN/GR- Ob rats also show infertility [4]. So they are propagated by mating fertile heterozygous carrier (+/−) littermates, which produces three phenotypes: the homozygous lean (+/+), the heterozygous carrier (+/−), and the homozygous obese (−/−) in a 1 : 2 : 1 Mendelian ratio. The biochemical indices of obesity like insulin, triglyceride, cholesterol, and leptin were also found to be high in these strains [2, 3]. Altered reproductive function leading to infertility is normally seen in obese animals as well as humans, both in males and females. For example, in women, obesity is frequently associated with menstrual disturbances with a high risk of androgenic ovulatory dysfunction and polycystic ovary syndrome [5–9]. Obese men, on the other hand, exhibit low serum testosterone, and testosterone injections in such people were shown to restore fertility and also bring about weight reduction [10]. Concerning to animals, studies in obese male Zucker rats at various ages (4, 6, and 10 months) revealed inadequate sexual behavior [11], with low pituitary weight and low concentration of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) [12, 13]. The animals also showed low testis weight, low levels of circulating testosterone, and low weights of levator ani (LA) muscle [14], which are androgen dependent. In the present study, we looked for anatomical and physi- ological changes in the reproductive organs of these animals,