Abstract
BackgroundRats made hypothyroid with propilthyouracil start showing abnormal cycling on the second cycle after the start of the treatment, with a high proportion of spontaneous pseudopregnancies and reduced fertility.MethodsTo investigate some of the mechanisms involved in these reproductive abnormalities, hypothyroidism was induced in virgin rats by propilthyouracil (0.1 g/L in the drinking water) and we determined circulating hormones by radioimmunoassay and whole ovary expression of ovarian hormone receptors, growth factors and steroidogenic enzymes using semi-quantitative RT-PCR.The study was performed on days 6 to 9 of treatment, corresponding to diestrus I (at 20.00-22.00 h), diestrus II (at 20.00-22.00 h), proestrus and estrus (both at 8.00-10.00 h and 20.00-22.00 h) of the second estrous cycle after beginning propilthyouracil treatment. Another group of rats was mated on day 8 and the treatment continued through the entire pregnancy to evaluate reproductive performance.ResultsHypothyroidism increased circulating prolactin and estradiol on estrus 5 to 7-fold and 1.2 to 1.4-fold respectively. Growth hormone and insulin-like growth factor 1 diminished 60 and 20% respectively on proestrus morning. Hypothyroidism doubled the ovarian mRNA contents of estrogen receptor-beta on proestrus and estrus evenings, cyp19A1 aromatase mRNA on estrus evening and of growth hormone receptor on proestrus evening. Hypothyroidism did not influence ovulation rate or the number of corpora lutea at term, but a diminished number of implantation sites and pups per litter were observed (Hypothyroid: 11.7 +/- 0.8 vs. Control: 13.9 +/- 0.7).ConclusionsShort term hypothyroidism alters normal hormone profile in the cycling rat increasing the expression of estrogen receptor-beta and cyp19A1 aromatase on estrus, which in turn may stimulate estradiol and prolactin secretion, favouring corpus luteum survival and the subsequent instauration of pseudopregnancy.
Highlights
Rats made hypothyroid with propilthyouracil start showing abnormal cycling on the second cycle after the start of the treatment, with a high proportion of spontaneous pseudopregnancies and reduced fertility
To investigate the biochemical mechanisms involved in the reproductive alterations observed in HypoT rats, we studied the early effects of PTU-induced hypothyroidism on the female reproductive axis analyzing its effect on basic reproductive parameters and ovarian function in virgin rats on the second cycle after beginning antithyroid treatment, that is the cycle when the rats were mated on our previous study [14]
Effect of PTU treatment on serum concentrations of thyroid, pituitary and ovarian hormones and IGF 1 PTU treatment was effective in inducing hypothyroidism, as shown by the diminished levels of T3 and T4 and elevated levels of thyroid stimulating hormone (TSH) (Figure 1)
Summary
Rats made hypothyroid with propilthyouracil start showing abnormal cycling on the second cycle after the start of the treatment, with a high proportion of spontaneous pseudopregnancies and reduced fertility. Hypothyroidism has a prevalence of 0.2 and 2% in male and female populations respectively [1], and if left untreated has severe consequences on the metabolism and function of various organs and systems of the organism, among them the reproductive system [2]. It has been associated with menstrual abnormalities, anovulation and hyperprolactinemia [3], which produce ovulation disorders and reduced fertility in women of childbearing age, with increased risk of miscarriage, premature delivery, placental abruption and poor perinatal outcome with low birth weight [4,5,6,7]. It is conceivable that THs play an essential role in ovarian physiology [12]
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