Perinatal administration of bisphenol A alters the expression of tight junction proteins in the uterus and reduces the implantation rate.

We studied the effect of bisphenol-A (BPA) administration to rats, during the perinatal period, on the fertility of F1 generation and on the expression of tight junction (TJ) proteins in the uterus during early pregnancy. Pregnant Wistar dams (F0) received: BPA-L (0.05mg/kg/day), BPA-H (20mg/kg/day) or vehicle, from gestational day (GD) 6 to lactation day 21. F1 female pups were mated at 3 months of age and sacrificed at GD 1, 3, 6, and 7. Serum hormonal levels, ovulation rate, number of implantation sites and expression of TJ proteins in the uterus of F1 females were evaluated. BPA treatment induced no change in ovulation rate, but induced alterations in progesterone (P4) and estradiol (E2) serum levels, and in implantation rate. With regards to TJ proteins, BPA-H increased claudin-1 during all GDs; eliminated the peaks of claudins -3 and -4 at GD 3 and 6, respectively; and decreased claudin-7 at GD 6, ZO-1 from GD 1-6, and claudin-3 at GD 7 in stromal cells. BPA-L instead, eliminated claudin-3 peak at GD 3, increased claudin-4 and decreased claudin-7 from GD 1-6, decreased claudin-1 at GD 3 and 7 and claudin-4 at GD 7 in stromal cells. BPA-L also decreased ZO-1 at GDs 1 and 3 and increased ZO-1 at GD 6. Thus, BPA treatment during perinatal period perturbed, when the animals reached adulthood and became pregnant, the particular expression of TJ proteins in the uterine epithelium and reduced in consequence the number of implantation sites.

The acute asymmetric effects of hemiovariectomy on testosterone secretion vary along the estrous cycle. The participation of the cholinergic system.

The presence of asymmetry in the capacity of the left and right ovaries to secrete testosterone was analyzed by studying the effects of hemiovariectomy along the estrus cycle one hour after surgery. The effects of ether anesthesia on hormone serum levels were also analyzed. Bilateral ovariectomy and the extirpation of the left ovary performed on the day of proestrus resulted in significantly lower testosterone levels. Compared to the anesthetized group, the effects of perforating the peritoneum unilaterally varied according to the day of the estrous cycle and the side of the peritoneum surgery was performed on. Injecting atropine sulfate (ATR) to control or anesthetized rats on D1 resulted in a significant increase of testosterone serum levels. The effects of perforating the peritoneum on testosterone levels depended on the cholinergic innervation and varied along the estrous cycle. Blocking the cholinergic system before performing unilateral or bilateral ovariectomy had different effects depending on the day of the estrous cycle. Testosterone plasma levels increased significantly when surgery was performed on the day of diestrus and dropped when surgery was performed on proestrus. Similar effects were observed when the left adrenal was extirpated from animals with the cholinergic system blocked. The results presented herein support the hypothesis of asymmetry in the ovaries' abilities to secrete steroid hormones, and that the capacity to secrete testosterone varies along the estrous cycle.

The participation of the cholinergic system in regulating progesterone secretion through the ovarian-adrenal crosstalk varies along the estrous cycle.

This study was designed to analyze the acute effects of unilateral or bilateral ovariectomy or adrenalectomy, performed on different days of the estrous cycle, on progesterone (P4) serum levels 1 h after surgery. The effects of blocking the cholinergic system by injecting atropine sulfate were also analyzed. Ether anesthesia treatment on diestrus 1 (D1) increased P4 serum levels. Compared to right sham-operated animals, right ovariectomy (left ovary in situ) performed on diestrus 2 (D2) or proestrus (P), resulted in P4 serum levels increase. Compared to animals with left sham surgery, left adrenalectomy (right adrenal in situ) performed on P day resulted in significantly lower P4 concentrations. Bilateral adrenalectomy resulted in a significant drop of P4 serum levels; the most remarkable drop was observed in animals treated on D2. Bilateral ovariectomy performed on D1 resulted in lower P4 serum levels, and the same treatment performed on P resulted in a significant rise of P4 serum levels. Injecting atropine sulfate to untouched (control group) rats resulted in significantly higher P4 concentrations. Blocking the cholinergic sys-tem on D1 or P to rats with the right adrenal removed resulted in lower P4 serum levels; while, in contrast, atropine sulfate treatment performed on D2 resulted in P4 serum levels increase. The results support the hypothesis of asymmetry in the ovaries' and adrenals' capacities to secrete P4; that this capacity varies along the estrous cycle; and that P4 secretion by the ovaries and adrenals is regulated by the cholinergic system.